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1.
Integr Cancer Ther ; 17(4): 1297-1303, 2018 12.
Article in English | MEDLINE | ID: mdl-30193538

ABSTRACT

The prognosis of triple-negative breast cancer with metastases after chemotherapy remains dismal. We report the case of a 50-year-old female with first disease recurrence at the axillary lymph node and, later on, bilateral pulmonary metastases with severe shortness of breath. The patient received low-dose immune checkpoint blockade (concurrent nivolumab and ipilimumab) weekly over 3 weeks with regional hyperthermia 3 times a week, followed by systemic fever-range hyperthermia induced by interleukin-2 for 5 days. She went into complete remission of her pulmonary metastases with transient WHO I-II diarrhea and skin rash. The patient remained alive for 27 months after the start of treatment, with recurrence of metastases as a sternal mass, and up to 3 cm pleural metastases. This exceptional response should instigate further research efforts with this protocol, which consists only of approved drugs and treatments.


Subject(s)
Fever/physiopathology , Interleukin-2/therapeutic use , Lung Neoplasms/drug therapy , Triple Negative Breast Neoplasms/drug therapy , Female , Humans , Lymph Nodes/drug effects , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Remission Induction/methods
2.
Obes Surg ; 25(12): 2268-75, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25910982

ABSTRACT

BACKGROUND: Impairment of gastric digestion due to pH elevation increases the risk for food allergy induction. As patients after Roux-en-Y gastric bypass (RYGB) surgery have lower gastric acidity and less gastric gland secretion, we aimed to analyse in a prospective study the effect of limiting gastric digestion capacity by surgical intervention on the immune response towards allergens. METHODS: Nine patients undergoing RYGB surgery for morbid obesity and one control patient having undergone surgery for treatment of an incisional hernia were enrolled in the study. Before and 1, 3, 6, 9 and 12 months after surgery, blood was collected for analysis of specific IgE antibodies, and patients were subjected to skin prick testing with 16 food and 18 aeroallergens. RESULTS: Skin prick test results revealed an increase of positive reactions indicating sensitisations towards the tested food and aeroallergens in 77.8 and 88.9 % of the patients, respectively, after surgical elimination of gastric digestion. These results were in line with elevated titers of food- and aeroallergen-specific IgE antibodies in 7 out of 9 (7/9) and 5/9 patients, respectively, after RYGB surgery. Serum cytokine levels revealed a mixed response for IFN-γ and were mostly beneath detection limit for IL-4. CONCLUSION: A change of IgE reactivity pattern occurred after impairment of gastric digestion due to surgical elimination underlining the important gastric gatekeeping function during oral sensitisation. Even though this study indicates an increased allergy risk for gastric bypass patients, further studies are needed to investigate in-depth the immunological changes associated with RYGB surgery.


Subject(s)
Digestion/physiology , Food Hypersensitivity/etiology , Gastric Bypass/adverse effects , Obesity, Morbid/surgery , Stomach/surgery , Adolescent , Adult , Case-Control Studies , Female , Food , Gastric Bypass/methods , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Stomach/physiopathology , Young Adult
3.
Obes Surg ; 25(7): 1198-202, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25491913

ABSTRACT

BACKGROUND: Paralleling the growth of bariatric surgery, the demand for post-bariatric body-contouring surgery is increasing and placing additional burdens on already strained health care systems. In Austria, medically necessary body contouring is covered by public health care. In a sample of 622 women, we assessed the proportion of patients that underwent post-bariatric surgery at least 2 years after gastric bypass. METHODS: Former bariatric patients were asked whether they had undergone post-bariatric surgery or were planning to do so by structured telephone interviews. For patients who had undergone body contouring, the degree of satisfaction with the results was inquired. Costs for bariatric and post-bariatric procedures were assessed. RESULTS: Of 622 patients, 93 (14.9 %) had undergone body contouring and 68 (10.9 %) considered a procedure, while 454 (73 %) definitely stated that they did not want plastic surgery. Cost coverage was declined in 7 patients (1.1 %). Plastic procedures (n = 101) included 65 abdominoplasties, 25 lower body lifts without thigh lifts, 7 brachioplasties, and 4 minor procedures. Forty-nine patients were very satisfied with the results, 28 were fairly satisfied, and 16 were not satisfied. Body contouring added about 6 % to the costs of surgical treatment for morbid obesity. CONCLUSIONS: Fewer patients than in other studies expressed a desire for post-bariatric surgery, 15 % actually proceeded to this step. The low demand was neither due to denied coverage nor to unfavourable results of plastic surgery. Additional costs for body contouring were less than expected.


Subject(s)
Bariatric Surgery/economics , Health Services Needs and Demand , Obesity, Morbid/surgery , Patient Satisfaction , Plastic Surgery Procedures/economics , Abdominoplasty/economics , Abdominoplasty/methods , Adult , Austria , Bariatric Surgery/methods , Female , Humans , Middle Aged , Motivation , Obesity, Morbid/economics , Plastic Surgery Procedures/methods , Treatment Outcome , Weight Loss
4.
Am J Clin Nutr ; 96(5): 1137-49, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23034965

ABSTRACT

BACKGROUND: Chronic adipose tissue inflammation is a hallmark of obesity, triggering the development of associated pathologies, particularly type 2 diabetes. Long-chain n-3 PUFAs reduce cardiovascular events and exert well-established antiinflammatory effects, but their effects on human adipose tissue inflammation are unknown. OBJECTIVE: We investigated whether n-3 PUFAs reduce adipose tissue inflammation in severely obese nondiabetic patients. DESIGN: We treated 55 severely obese nondiabetic patients, scheduled to undergo elective bariatric surgery, with 3.36 g long-chain n-3 PUFAs/d (EPA, DHA) or an equivalent amount of butterfat as control, for 8 wk, in a randomized open-label controlled clinical trial. The primary efficacy measure was inflammatory gene expression in visceral and subcutaneous adipose tissue samples (subcutaneous adipose tissue and visceral adipose tissue), collected during surgery after the intervention. Secondary efficacy variables were adipose tissue production of antiinflammatory n-3 PUFA-derived eicosanoids, plasma concentrations of inflammatory markers, metabolic control, and the effect of the Pro12Ala PPARG polymorphism on the treatment response. RESULTS: Treatment with n-3 PUFAs, which was well tolerated, decreased the gene expression of most analyzed inflammatory genes in subcutaneous adipose tissue (P < 0.05) and increased production of antiinflammatory eicosanoids in visceral adipose tissue and subcutaneous adipose tissue (P < 0.05). In comparison with control subjects who received butterfat, circulating interleukin-6 and triglyceride concentrations decreased significantly in the n-3 PUFA group (P = 0.04 and P = 0.03, respectively). The Pro12Ala polymorphism affected the serum cholesterol response to n-3 PUFA treatment. CONCLUSIONS: Treatment with long-chain n-3 PUFAs favorably modulated adipose tissue and systemic inflammation in severely obese nondiabetic patients and improved lipid metabolism. These effects may be beneficial in the long-term treatment of obesity. This trial was registered at clinicaltrials.gov as NCT00760760.


Subject(s)
Adipose Tissue/drug effects , Fatty Acids, Omega-3/administration & dosage , Inflammation/drug therapy , Obesity/drug therapy , Adipose Tissue/physiology , Adult , Aged , DNA/chemistry , DNA/genetics , Fatty Acids/blood , Female , Humans , Immunohistochemistry , Inflammation/blood , Inflammation/genetics , Interleukin-6/blood , Male , Middle Aged , Obesity/blood , Obesity/genetics , PPAR gamma/genetics , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Triglycerides/blood , Young Adult
5.
Obes Surg ; 22(4): 544-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22101887

ABSTRACT

BACKGROUND: Massive weight loss following bariatric surgery leads to excess skin with functional and aesthetic impairments. Surplus skin can then contribute to problems with additional weight loss or gain. The aims of the current study were to evaluate the frequency of massive soft tissue development in gastric bypass patients, to determine whether males and females experience similar post-bypass body changes, and to learn about the expectations and impairments related to body contouring surgery. METHODS: A questionnaire addressing information on the satisfaction of body image, quality of life, and expectation of body contouring surgery following massive weight loss was mailed to 425 patients who had undergone gastric bypass surgery between 2003 and 2009. Of these 425 individuals, 252 (59%) patients completed the survey. RESULTS: Ninety percent of women and 88% of men surveyed rated their appearance following massive weight loss as satisfactory, good, or very good. However, 96% of all patients developed surplus skin, which caused intertriginous dermatitis and itching. In addition, patients reported problems with physical activity (playing sports) and finding clothing that fit appropriately. Moreover, 75% of female and 68% of male patients reported desiring body contouring surgery. The most important expectation of body contouring surgery was improved appearance, followed by improved self-confidence and quality of life. CONCLUSIONS: Surplus skin resulting from gastric bypass surgery is a common issue that causes functional and aesthetic impairments in patients. Consequently, this increases the desire for body contouring surgery with high expectations for the aesthetic outcome as well as improved life satisfaction.


Subject(s)
Bariatric Surgery/psychology , Body Image , Dermatologic Surgical Procedures , Patient Satisfaction , Plastic Surgery Procedures/psychology , Quality of Life , Weight Loss , Austria/epidemiology , Bariatric Surgery/adverse effects , Bariatric Surgery/methods , Esthetics , Female , Humans , Male , Middle Aged , Needs Assessment , Outcome Assessment, Health Care , Patient Satisfaction/statistics & numerical data , Plastic Surgery Procedures/methods , Self Concept , Surveys and Questionnaires
6.
Obes Surg ; 22(1): 8-12, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21643778

ABSTRACT

BACKGROUND: As bariatric surgery has become more popular, more patients are undergoing body contouring surgery after massive weight loss. Many of the surgical procedures performed on the massive weight loss patient are complex and labor-intensive. Therefore, the plastic surgery unit needs to be prepared for a patient's demand. Little literature is available on how frequently patients who have undergone gastric bypass surgery receive body contouring surgery. METHODS: Two hundred fifty-two subjects (out of 425 who were mailed the questionnaire) who had undergone gastric bypass surgery between 2003 and 2009 completed the questionnaire, which obtained information on body image satisfaction and frequency of body contouring surgery after massive weight loss. RESULTS: Of all patients, 74% desire a body contouring surgery after gastric bypass surgery. Fifty-three patients (21%) have undergone a total of 61 body contouring procedures. The most common were abdominoplasties (59%), followed by lower body lifts (20%). In contrast to a positive judgment of the general aspect of the body image satisfaction after massive weight loss, both genders are unsatisfied with body areas like abdomen/waist, breast, and thighs. CONCLUSIONS: Paralleling the increasing use of bariatric surgery, there is a high demand for body contouring surgery. A huge disparity exists between the number of subjects who desire a body contouring surgery and those who actually received it.


Subject(s)
Dermatologic Surgical Procedures , Gastric Bypass/statistics & numerical data , Obesity, Morbid/surgery , Patient Satisfaction/statistics & numerical data , Surgery, Plastic/statistics & numerical data , Weight Loss , Abdomen/surgery , Austria/epidemiology , Body Image , Breast/surgery , Female , Follow-Up Studies , Gastric Bypass/adverse effects , Gastric Bypass/psychology , Humans , Male , Middle Aged , Obesity, Morbid/epidemiology , Obesity, Morbid/psychology , Prevalence , Surgery, Plastic/psychology , Surveys and Questionnaires , Thigh/surgery , Time Factors
8.
Obes Surg ; 20(7): 835-40, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20393810

ABSTRACT

BACKGROUND: Due to excellent weight loss success in the short-time follow-up, sleeve gastrectomy (SG) has gained popularity as sole and definitive bariatric procedure. In the long-term follow-up, weight loss failure and intractable severe reflux can necessitate further surgical intervention. METHODS: A retrospective analysis of laparoscopic conversions from SG to Roux-en-Y gastric bypass (RYGB) was performed to assess the efficacy for reflux relief and weight loss success. RESULTS: A total of eight out of 73 patients (11%) underwent conversion to RYGB for severe reflux (n=3) or weight regain (n=5) after a median interval of 33 months following laparoscopic sleeve gastrectomy. In one of the patients, a banded gastric bypass was performed. In both groups, conversion to RYGB was successful, as proton pump inhibitor medication could be discontinued in all patients presenting with severe reflux, and a significant weight loss could be achieved in the patients with weight regain within a median follow-up of 33 months. Postoperative complications were observed in only one patient as leakage at the gastrojejunostomy was successfully treated by temporary stent placement. CONCLUSION: Conversion to RYGB is an effective treatment for weight regain or intractable reflux symptoms following SG. Thus, SG can be performed, intended as sole and definitive bariatric intervention, with conversion from SG to RYGB as an exit strategy for these complications.


Subject(s)
Anastomosis, Roux-en-Y/methods , Gastrectomy/methods , Gastric Bypass/methods , Laparoscopy/methods , Obesity, Morbid/surgery , Adolescent , Adult , Female , Follow-Up Studies , Gastrectomy/adverse effects , Gastroesophageal Reflux/surgery , Humans , Laparoscopy/adverse effects , Male , Retrospective Studies , Stomach/surgery , Time Factors , Treatment Outcome , Weight Loss , Young Adult
9.
Obes Surg ; 20(5): 535-40, 2010 May.
Article in English | MEDLINE | ID: mdl-20094819

ABSTRACT

BACKGROUND: Due to excellent efficacy for weight loss in the short-term follow-up, sleeve gastrectomy (SG) has gained enormous popularity as bariatric procedure, not only as first step in high-risk or super-obese patients but mainly as a sole and definitive operation in morbidly obese. In contrast to a large number of short and intermediate-term results, no series of SG with a follow-up of 5 years or more has been published so far. METHODS: We report on the weight loss results of our first consecutive 26 patients with a complete follow-up of 5 years. Furthermore in a subgroup of 12 patients, plasma ghrelin levels were measured preoperatively, and up to 5 years following SG. RESULTS: Weight loss defined as mean percent excess weight loss (%EWL) was found as 57.5 +/- 4.5, 60.3 +/- 5.0, 60.0 +/- 5.7, 58.4 +/- 5.4, and 55.0 +/- 6.8 (not converted, n = 21) for the first 5 years. Weight regain of more than 10 kg from nadir was observed in five (19.2%) of the 26 patients. Four of the patients (15.4%) were converted to gastric bypass due to severe reflux (n = 1, 3.8%) and weight loss failure (n = 3, 11.5%). A total of eight patients (30.8%) were at chronic need for proton pump inhibitor medication due to severe reflux. Plasma ghrelin levels were reduced from 593 +/- 52 to 219 +/- 23 pg/ml 12 months postoperatively, with a slightly, non-significant increase toward the 5-years values of mean 257 +/- 23 pg/ml. CONCLUSIONS: At 5-year follow-up, a mean EWL of 55.0 +/- 6.8% was achieved, indicating that SG leads to stable weight loss. Beside significant weight regain, severe reflux might necessitate conversion to gastric bypass or duodenal switch. After an immediate reduction postoperatively, plasma ghrelin levels remained low for the first 5 years postoperatively.


Subject(s)
Gastrectomy/methods , Ghrelin/blood , Obesity, Morbid/surgery , Weight Loss/physiology , Body Mass Index , Female , Follow-Up Studies , Humans , Male , Middle Aged , Treatment Outcome
10.
Obes Surg ; 20(4): 440-6, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19856035

ABSTRACT

BACKGROUND: Different surgical techniques have been developed for the gastrojejunostomy (GJS) in laparoscopic Roux-en-Y gastric bypass (LRYGBP) with the anastomosis performed in a circular-stapled, linear-stapled, or totally hand-sewn way. No technique seems superior to the other as no consistent data on weight loss or complication rates were described. METHODS: A matched-pair study was conducted including a total of 150 patients, who underwent primary antegastric, antecolic LRYGBP between August 2003 and February 2007. Early weight loss and the incidence of GJS strictures or leaks and wound infections were compared between circular-stapled anastomosis (CSA) and linear-stapled anastomosis (LSA). Both groups were matched for age, sex, and body mass index. RESULTS: Excess weight loss at 3 months was slightly better with the CSA (p = 0.002) and comparable thereafter. Percentage of excess weight loss at 6, 12, and 24 months was 55.9 +/- 17.5% vs. 51.2 +/- 14.5%, 69.5 +/- 20.9% vs. 71.4 +/- 22.6%, and 70.8 +/- 22.4% vs. 73.2 +/- 23.4%, respectively (CSA vs. LSA). Strictures at the GJS were found only in the CSA group (n = 4), and leaks were found in one patient of the CSA group. More wound infections were observed in patients of the CSA group (ten vs. one). CONCLUSIONS: CSA and LSA lead to comparable early weight loss in LRYGB. Thus, the technique is the surgeon's choice. In CSA, a higher incidence of GJS strictures and wound infections was observed. As weight regain following LRYGBP is commonly observed after at least 3 years, a longer follow-up is needed to compare the incidence of weight regain in circular- vs. linear-stapled GJS.


Subject(s)
Gastric Bypass/methods , Adult , Constriction, Pathologic/etiology , Female , Gastric Bypass/adverse effects , Humans , Laparoscopy , Male , Middle Aged , Surgical Stapling/adverse effects , Surgical Stapling/methods , Surgical Wound Infection/etiology , Weight Loss
11.
Obes Surg ; 19(9): 1221-7, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19575272

ABSTRACT

BACKGROUND: Gastric electrical stimulation synchronized to the refractory period of gastric electrical activity and applied during meals was evaluated for safety and for improvement of body weight and glycemic control in obese type 2 diabetes. METHODS: The study involved obese diabetic type 2 (ODM) patients in a multicenter open-label European feasibility trial. A total of 24 ODM (nine males, 15 females) treated with insulin and/or oral hyperglycemic agents and body mass index between 33.3 to 49.7 kg/m(2) were implanted laparoscopically with a TANTALUS system. RESULTS: There were 18 adverse events related to the implant procedure or the device reported in 12 subjects. All were short lived and resolved with no sequelae. In the 21 subjects that reached the 1-year visit weight was reduced by 4.5 +/- 2.7 kg (p < 0.05) and HbA1c by 0.5 +/- 0.3% (p < 0.05). In a subgroup (n = 11) on stable or reduced oral medication, weight was reduced by 6.3 +/- 3.4 kg (p < 0.05) and HbA1c by 0.9 +/- 0.4% (p < 0.05). The group on insulin (n = 6) had no significant changes in weight and HbA1c. CONCLUSIONS: The TANTALUS system is well tolerated in obese type 2 diabetic subjects. Gastric electrical stimulation can potentially improve glucose metabolism and induce weight loss in obese diabetic patients, who are not well controlled on oral antidiabetic therapy. Further evaluation is required to determine whether this effect is due to induced weight loss and/or to direct signal dependent mechanisms.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/therapy , Electric Stimulation Therapy , Obesity, Morbid/metabolism , Obesity, Morbid/therapy , Adolescent , Adult , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/complications , Electrodes, Implanted , Feasibility Studies , Feeding Behavior , Female , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/therapeutic use , Male , Middle Aged , Obesity, Morbid/complications , Treatment Outcome , Weight Loss , Young Adult
12.
Clin Chim Acta ; 394(1-2): 67-71, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18474232

ABSTRACT

BACKGROUND: In an attempt to monitor the pharmacodynamics of mycophenolate mofetil (MMF) we investigated the association of inosine monophosphate dehydrogenase (IMPDH) activity in peripheral blood mononuclear cells with the expression of lymphocyte activation markers in stable cardiac transplant recipients treated with MMF. METHODS: Twenty-four study patients were switched from azathioprine to MMF 7.2+/-4.1 years after heart transplantation. RESULTS: While the MPA trough level remained unchanged, the mean activity of IMPDH declined from 890 to 462 pmol/10(6)PBMC/h three months after onset of MMF therapy, was almost completely inhibited at six months and partially restored to 160 pmol/10(6)PBMC/h 12 months after switch to MMF (p< .0001). We detected also significant changes in a number of activated lymphocyte subsets: CD4+/25+, CD8+/38+, CD19+/69+, CD3+/16+/56+, natural killer (NK) cells, and monocytes. Moreover, the IMPDH activity profile correlated positively with the number of CD8+/38+ T cells (correlation coefficient (CC) +0.53), and inversely with NK cells (CC -0.52) and CD19+/69+ cells (CC -0.61). CONCLUSIONS: We revealed a close association of IMPDH baseline activity in mononuclear cells with the expression of lymphocyte activation markers in stable heart transplant patients after introduction of MMF therapy. This supports the assumption of a rather immunomodulatory than immunosuppressive effect of MMF.


Subject(s)
IMP Dehydrogenase/metabolism , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Mycophenolic Acid/analogs & derivatives , Adult , Female , Heart Transplantation , Humans , Male , Middle Aged , Mycophenolic Acid/pharmacology
13.
Resuscitation ; 75(3): 445-53, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17640792

ABSTRACT

AIM: To evaluate the frequency, presentation, treatment and outcome of cardiopulmonary resuscitation-associated major liver injury in patients after non-traumatic in- or out-of-hospital cardiac arrest. MATERIALS AND METHODS: Retrospective analysis of a cardiac arrest registry in a tertiary care hospital emergency department. We reviewed patients charts, laboratory data, diagnostic imaging studies and autoptic findings. RESULTS: Within 14.5 years, major liver injury (rupture/laceration, haemorrhage/haematoma) was found in 15 of 2558 cardiac arrest victims (0.6%). Eleven were male (73%), median age was 58 (IQR 53-67). In seven, resuscitation was started out-of-hospital. In 9 of the 15 patients, liver injury was correctly diagnosed intra vitam. In 5, haematocrit level was low on admission, in 8 haematocrit dropped significantly during observation; haemostasis was compromised in 13 patients, 4 of them receiving thrombolytic therapy. Bedside abdominal sonography showed free intra-peritoneal fluid in 8 of 9 cases examined. In 11 patients, we found liver rupture/laceration, in 4 liver haemorrhage/haematoma. The site of injury was the left liver lobe in 11, six underwent emergent surgery. Two of 15 patients survived to 6 months in good neurological condition, 1 after emergency surgery. No patient died from bleeding due to liver injury. CONCLUSION: Our single centre observation confirms that resuscitation-associated major liver injury is infrequent and shows that most patients had compromised haemostasis. Low or dropping haematocrit should trigger suspicion. Bedside sonography reveals intra-peritoneal fluid or liver injury. A conservative therapeutic approach or emergency surgery may be warranted. Major liver injury alone scarcely appears to influence overall outcome.


Subject(s)
Cardiopulmonary Resuscitation/adverse effects , Cardiopulmonary Resuscitation/statistics & numerical data , Heart Arrest/therapy , Liver/injuries , Wounds, Nonpenetrating/etiology , Adult , Aged , Contusions , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Lacerations , Male , Middle Aged , Registries , Retrospective Studies , Rupture , Severity of Illness Index , Treatment Outcome , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/therapy
14.
J Clin Endocrinol Metab ; 92(3): 1168-71, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17164313

ABSTRACT

CONTEXT: Administration of retinol-binding protein 4 (RBP-4) impairs insulin sensitivity in animals, and elevated serum concentrations have been associated with insulin resistance in humans. OBJECTIVE: We have studied whether weight loss influences RBP-4. PATIENTS AND METHODS: Fasting serum concentrations of RBP-4 were measured before and 6 months after gastric banding surgery in 33 morbidly obese patients aged 40 +/- 11 yr with a body mass index (BMI) of 46 +/- 5 kg/m(2). Fourteen healthy subjects aged 29 +/- 5 yr with a BMI less than 25 kg/m(2) served as controls. To characterize the association of weight loss with central and peripheral appetite regulation, the signaling protein agouti-related protein (AGRP), the orexigenic hormone ghrelin, and its recently identified antagonist obestatin were determined. RESULTS: At baseline, RBP-4 levels were markedly higher in obese than in lean subjects (2.7 +/- 0.5 vs. 0.9 +/- 0.5 microg/ml; P < 0.001). In contrast, AGRP and obestatin were lower in obese subjects compared with lean controls (all P < 0.001). Six months after gastric banding, BMI was reduced to 40 +/- 5 kg/m(2), RBP-4 was reduced to 2.0 +/- 0.7 microg/ml, AGRP increased from 1.8 +/- 1.1 to 3.4 +/- 1.1 ng/ml, ghrelin increased from 93 +/- 58 to 131 +/- 70 pg/ml, and obestatin increased from 131 +/- 52 to 173 +/- 35 pg/ml (all P < 0.05). Individual changes of RBP-4 were associated with changes of BMI (r = 0.72), the homeostasis model assessment insulin resistance-index (r = 0.53), and total cholesterol (r = 0.42, for all P < 0.05). CONCLUSION: Reductions in circulating RBP-4 may contribute to improved insulin resistance in morbidly obese subjects after weight loss. This is accompanied by favorable changes in appetite-regulating hormones, which might support the sustained weight loss after obesity surgery.


Subject(s)
Obesity, Morbid/blood , Obesity, Morbid/surgery , Retinol-Binding Proteins/analysis , Weight Loss/physiology , Adult , Bariatric Surgery , Blood Glucose/analysis , Female , Humans , Insulin/blood , Insulin Resistance , Male , Middle Aged , Retinol-Binding Proteins, Plasma
15.
Transplantation ; 82(1): 113-8, 2006 Jul 15.
Article in English | MEDLINE | ID: mdl-16861950

ABSTRACT

BACKGROUND: The objective of this study was to investigate purine nucleotide metabolism in peripheral blood mononuclear cells (PBMC) of cardiac transplant recipients switched from azathioprine to mycophenolate mofetil (MMF). METHODS: Concentrations of guanosine 5'triphosphate (GTP) and adenosine 5'triphosphate (ATP), the activities of inosine monophosphate dehydrogenase (IMPDH), guanine phosphoribosyltransferase (GPRT), and hypoxanthine phosphoribosyltransferase (HPRT) were determined in PBMC of 27 cardiac transplant recipients before switch to MMF and 3, 6, and 12 months thereafter. RESULTS: There was no difference in the activities of IMPDH and salvage pathway enzymes GPRT and HRPT as well as in intracellular GTP and ATP concentrations between the patients before switch to MMF and healthy controls. The GTP and ATP concentrations in PBMC of cardiac recipients did not change during the entire observation period. Although the MPA trough level remained similar, IMPDH activity declined from 897 to 316 pmol/10(6)PBMC/h 3 months after MMF onset, was almost completely inhibited after 6 months, and partially restored to 143 pmol/10(6)PBMC/h 12 months after switch to MMF. In contrast, GPRT activity increased after 3, 6, and 12 months of MMF therapy and HPRT activity 3 and 6 months after switch to MMF. CONCLUSIONS: We demonstrated for the first time an induction of salvage pathway enzyme activities in PBMC under MMF therapy. This probably accounts for the maintenance of intracellular purine nucleotide pools and prevents the GTP depletion.


Subject(s)
Heart Transplantation , Hypoxanthine Phosphoribosyltransferase/metabolism , IMP Dehydrogenase/metabolism , Immunosuppressive Agents/administration & dosage , Mycophenolic Acid/analogs & derivatives , Purine Nucleotides/metabolism , Adenosine Triphosphate/analysis , Adenosine Triphosphate/metabolism , Adult , Aged , Azathioprine/administration & dosage , Enzyme Activation , Female , Guanosine Triphosphate/analysis , Guanosine Triphosphate/metabolism , Humans , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/enzymology , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Purine Nucleotides/analysis
16.
Obes Surg ; 16(5): 627-34, 2006 May.
Article in English | MEDLINE | ID: mdl-16687033

ABSTRACT

BACKGROUND: Increased caloric density in modern processed foods may be an important factor underlying the prevalence of obesity, because low-volume, high-caloric food intake may delay activation of volume-dependent gastric mechanical activity known to induce the feeling of fullness. We therefore hypothesized that enhancement of gastric contractions by electrical stimulation at an early stage of the meal will reduce food intake and body weight in morbidly obese subjects. METHODS: The study was a prospective, non-randomized, open-label, single-center trial. 12 subjects (age 36.1 +/- 2.8 years, BMI 43.2 +/- 2.7 kg/m(2), weight 128.8 +/- 5.2 kg, means+/-SEM) underwent laparoscopic implantation with the Tantalus system. A pulse generator with 3 bipolar leads was implanted: 2 pairs in the antrum and a 3rd pair in the fundus. The system was activated at week 6. All subjects were followed for 20 weeks and 9 of them for 52 weeks. RESULTS: All subjects finished the initial 20-week observation period. Following activation of the Tantalus System, a reduction (P<0.05) in hunger and an increase in cognitive control (P<0.05) as assessed by the Three-Factor Eating Questionnaire (TFEQ) could be observed. Body weight decreased (P<0.05) from 128.8+/-5.2 to 119.9+5.9 (17.6+4.3% EWL, N=12) after 20 weeks (14 weeks of treatment). In the 9 subjects continuing for 52 weeks (46 weeks of treatment), body weight further decreased to 112.4 +/- 3.8 kg (26.6 +/- 8.5 %EWL, N=9). Blood pressure decreased (P<0.05) from 142 +/- 6.1/91 +/- 3.2 to 125.5 +/- 4.0/83 +/- 2.6 mmHg by week 20 and 128.8 +/- 3.8 / 86.3 +/- 3.6 mmHg after 1 year. The frequency and severity of device and/or procedure-related adverse events indicate that the method is safe and well-tolerated. CONCLUSION: This data suggests that gastric stimulation by the minimally invasive Tantalus System is safe and leads to favorable changes in eating behavior, clinically significant weight loss and reduction in blood pressure. Treatment with the Tantalus System is therefore a promising minimally invasive treatment for obesity.


Subject(s)
Electric Stimulation Therapy/methods , Adult , Blood Pressure , Electric Stimulation Therapy/instrumentation , Electrodes, Implanted , Electrophysiology , Feeding Behavior , Female , Humans , Hunger , Male , Muscle Contraction/physiology , Muscle, Smooth/physiopathology , Obesity, Morbid/physiopathology , Obesity, Morbid/therapy , Satiety Response , Treatment Outcome , Weight Loss
17.
Obes Surg ; 16(2): 166-71, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16469218

ABSTRACT

BACKGROUND: Sleeve gastrectomy as the sole bariatric operation has been reported for high-risk super-obese patients or as first-step followed by Roux-en-Y gastric bypass (RYGBP) or duodenal switch (DS) in super-super obese patients. The efficacy of laparoscopic sleeve gastrectomy (LSG) for morbidly obese patients with a BMI of <50 kg/m2 and the incidence of gastric dilatation following LSG have not yet been investigated. METHODS: 23 patients (15 morbidly obese, 8 super-obese) were studied prospectively for weight loss following LSG. The incidence of sleeve dilatation was assessed by upper GI contrast studies in patients with a follow-up of >12 months. RESULTS: Patients who underwent LSG achieved a mean excess weight loss (EWL) at 6 and 12 months postoperatively of 46% and 56%, respectively. No significant differences were observed in %EWL comparing obese and super-obese patients. At a mean follow-up of 20 months, dilatation of the gastric sleeve was found in 1 patient and weight regain after initial successful weight loss in 3 of the 23 patients. CONCLUSION: LSG has been highly effective for weight reduction for morbid obesity even as the sole bariatric operation. Gastric dilatation was found in only 1 patient in this short-term follow-up. Weight regain following LSG may require conversion to RYGBP or DS. Follow-up will be necessary to evaluate long-term results.


Subject(s)
Gastrectomy/methods , Gastric Dilatation/etiology , Laparoscopy/methods , Obesity, Morbid/surgery , Adult , Age Distribution , Aged , Body Mass Index , Female , Follow-Up Studies , Gastrectomy/adverse effects , Gastric Dilatation/epidemiology , Humans , Incidence , Laparoscopy/adverse effects , Male , Middle Aged , Obesity, Morbid/diagnosis , Probability , Prospective Studies , Risk Assessment , Severity of Illness Index , Sex Distribution , Statistics, Nonparametric , Treatment Outcome
18.
J Heart Lung Transplant ; 23(11): 1277-82, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15539126

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) has long been recognized as the most common opportunistic pathogen in transplant recipients. The use of post-detection antiviral treatment of CMV as a strategy to prevent disease in cardiac recipients is becoming the standard policy. Valganciclovir is an oral pro-drug of ganciclovir, with a 10-fold greater bioavailability than oral gancyclovir. PATIENTS AND METHODS: We reported our first experience with 8 patients (3 female, 45.0 +/- 10.5 years old, non-CMV mismatched) who underwent cardiac transplantation and had positive results of CMV polymerase chain reaction (PCR) within first 6 weeks after transplantation without concomitant CMV disease. These patients received valganciclovir in dosage 450 to 900 mg daily depending on renal function for 3 weeks. Standard immunosuppressive regimen consisted of cyclosporin A, MMF and corticosteroids, and was not changed after detection of CMV infection. In one patient we used sirolimus with respectively reduced dosage of cyclosporin A. Weekly measurements of CMV-PCR were performed to observe results of therapy. RESULTS: After 1 week of valganciclovir therapy CMV-PCR plasma concentration in all patients decreased significantly (2,105 copies/ml vs 400 copies/ml; p < 0.0001). No relapse of CMV infection has been detected after completing of valganciclovir therapy with follow up duration of 9.0 +/- 0.92 months. The drug was generally well tolerated, and we did not observe any severe drug related adverse events. CONCLUSION: Oral valganciclovir as pre-emptive antiviral therapy administrated after detection of CMV infection seems to be an effective and safe treatment in cardiac transplant recipients.


Subject(s)
Antiviral Agents/administration & dosage , Cytomegalovirus Infections/prevention & control , Ganciclovir/analogs & derivatives , Ganciclovir/administration & dosage , Heart Transplantation/adverse effects , Administration, Oral , Adult , Cytomegalovirus Infections/etiology , Female , Humans , Male , Middle Aged , Valganciclovir
19.
Wien Med Wochenschr ; 154(13-14): 329-33, 2004 Jul.
Article in German | MEDLINE | ID: mdl-15368954

ABSTRACT

At the beginning of the 21st century, obesity has become an epidemic with the greatest prevalence in the western world. For morbidly obese patients, conservative treatment has yielded disappointing results: On the other hand, bariatric surgery offers a sustained substantial weight loss for these patients. Common bariatric procedures including results and complications are described. Different Bariatric procedures including Gastric Banding, Vertical Banded Gastroplasty, Gastric Bypass, Duodenal Switch and Gastric Pacing are introduced. Bariatric procedures can result in permanent excessive weight loss ranging from 25 to 78% and thus are an effective treatment for morbidly obese patients. Efficacy, morbidity and late term complications, however, should be considered in choosing the most effective bariatric approach.


Subject(s)
Obesity/surgery , Biliopancreatic Diversion , Cross-Sectional Studies , Electric Stimulation Therapy/instrumentation , Electrodes, Implanted , Gastric Bypass , Gastroplasty , Humans , Laparoscopy , Obesity/epidemiology , Outcome and Process Assessment, Health Care
20.
Circulation ; 108 Suppl 1: II318-23, 2003 Sep 09.
Article in English | MEDLINE | ID: mdl-12970253

ABSTRACT

Predictors of adverse outcome after replacement of the ascending aorta with resection of the intimal tear and open distal anastomosis were analyzed in 167 patients (109 male, median age 56). Median hypothermic circulatory arrest (HCA) time was 30 minutes (range 12 to 113). Eighty-six patients (pts) had surgery within 24 hours and 81 within 72 hours of symptom onset. Thirty-seven pts had only ascending aortic replacement, 128 had hemiarch repair, and in 2 the entire arch was replaced. The aortic valve was replaced in 37 pts, resuspended in 116, and untouched in 14. Either death or permanent neurological dysfunction was considered an adverse outcome (AO). AO occurred in 30.5% (51/167) of patients overall. Multivariate analysis revealed that the only significant (P<0.05) independent preoperative predictor of AO was hemodynamic instability (OR 6.0). Transient neurological dysfunction (TND) occurred in 19 of 116 patients (16.4%). Significant predictors of TND were increasing age >60 (OR 3.4 and 7.0 in the second and third tertile as compared with the lowest tertile) and coronary heart disease (OR 3.4). Cumulative survival of patients (median follow-up 34 months) was 55% at 1, 49% at 5, and 44% at 8 years, indicating an excessive in-hospital mortality, but excellent long term outcome. Surgical treatment of acute type A dissections is still associated with a high incidence of adverse outcome, but results in excellent long-term survival. Earlier diagnosis, before the development of cardiac tamponade and hemodynamic compromise, is critical to improve the operative salvage rate.


Subject(s)
Aortic Aneurysm/surgery , Aortic Dissection/surgery , Nervous System Diseases/etiology , Postoperative Complications , Adolescent , Adult , Aged , Aortic Dissection/mortality , Aortic Aneurysm/mortality , Female , Humans , Male , Middle Aged , Nervous System Diseases/epidemiology , Postoperative Complications/mortality , Risk Factors , Survival Rate
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