ABSTRACT
Fibrous mats with hydrophobic and oleophilic properties have been fabricated and used as absorbents of oil from stable water in oil emulsions. The mats were prepared by initially mixing two polymers, poly(methyl methacrylate) (PMMA) and polycaprolactone (PCL), in a common solvent. The subsequent electrospinning of the prepared solutions resulted in the production of mechanically stable fiber mats, with enhanced oil absorption capacity and oil absorption selectivity from the emulsions, compared to the pure PMMA or PCL mats. Furthermore, the formed fibrous substrates have been successful in the absorption of oil from different emulsions with a wide range of oil content, from 10 to 80 v%. The performance of the fibrous mats was optimized by the incorporation of hydrophobic silica nanoparticles, reaching oil absorption capacities of 28 g g-1 and negligible water uptake, in the emulsions with 80 v% oil content.
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BACKGROUND: Free fatty acid (FFA) levels are raised in obesity as a consequence of increased production and reduced clearance. They may link obesity with insulin resistance. Bariatric surgery can result in considerable weight loss and reduced insulin resistance, but the mechanism of action is not well understood. Although drugs such as metformin that lower insulin resistance can contribute to weight loss, a better understanding of the links between obesity, weight loss and changes in insulin resistance might lead to new approaches to patient management. METHODS: Variations in circulating levels of leptin, insulin and FFAs over 24 h were studied in severely obese (body mass index over 40 kg/m(2) ) women before and 6 months after biliopancreatic diversion (BPD). Body composition was measured by dual-energy X-ray absorptiometry. A euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Levels of insulin, leptin and FFAs were measured every 20 min for 24 h. Pulsatile hormone and FFA analyses were performed. RESULTS: Among eight patients studied, insulin sensitivity more than doubled after BPD, from mean(s.d.) 39·78(7·74) to 96·66(27·01) mmol per kg fat-free mass per min, under plasma insulin concentrations of 102·29(9·60) and 93·61(9·95) µunits/ml respectively. The secretory patterns of leptin were significantly different from random but not statistically different before and after BPD, with the exception of the pulse height which was reduced after surgery. Both plasma insulin and FFA levels were significantly higher throughout the study day before BPD. Based on Granger statistical modelling, lowering of daily FFA levels was linked to decreased circulating leptin concentrations, which in turn were related to the lowering of daily insulin excursions. Multiple regression analysis indicated that FFA level was the only predictor of leptin level. CONCLUSION: Lowering of circulating levels of FFAs after BPD may be responsible for the reduction in leptin secretion, which in turn can decrease circulating insulin levels. Surgical relevance Insulin resistance is a common feature of obesity and type II diabetes. These patients are also relatively insensitive to the biological effects of leptin, a satiety hormone produced mainly in subcutaneous fat. Biliopancreatic diversion, a malabsorptive bariatric operation that drastically reduces circulating lipid levels, improves insulin resistance independently of weight loss. The mechanism of action, however, has still to be elucidated. This study demonstrated that normalization of insulin sensitivity after bariatric surgery was associated with a reduction in 24-h free fatty acid concentrations and changes in the pattern of leptin peaks in plasma. Bariatric surgery improves the metabolic dysfunction of obesity, and this may be through a reduction in circulating free fatty acids and modification of leptin metabolism.
Subject(s)
Biliopancreatic Diversion , Circadian Rhythm/physiology , Fatty Acids, Nonesterified/blood , Insulin/blood , Leptin/blood , Obesity, Morbid/surgery , Weight Loss/physiology , Adult , Body Mass Index , Female , Follow-Up Studies , Humans , Obesity, Morbid/blood , Prognosis , Time FactorsABSTRACT
BACKGROUND: A new modified-release (MR) granule formulation of valproate (VPA) has been recently developed for the treatment of children with epilepsy. It consists of tasteless microspheres that can be sprinkled on soft foods and easily swallowed. There are no data on the effectiveness of this formulation in pediatric age. AIM OF THE STUDY: To evaluate the effects of the abrupt switch from solution to VPA MR granules in children undergoing chronic treatment. METHODS: We enrolled children receiving VPA solution as sole or adjunctive therapy and switched them to MR granules at identical dosages. VPA blood level, treatment efficacy (clinical and EEG data), tolerability (adverse reactions), palatability, ease of administration, and compliance were evaluated before switching (T0) and after 4 weeks (T1). RESULTS: Out of 112 enrolled children, 108 (96.4%) completed the evaluation. We observed no significant differences between the patients at T0 and T1 in VPA blood levels, treatment efficacy, tolerability, and compliance. MR granules were judged more palatable (P < 0.05) and easier to administer (P < 0.05) than solution by children and parents. At 6-month follow-up, all patients continued to use MR granules. CONCLUSION: Modified-release granule formulation of VPA may be a reliable alternative to solution for its convenience of use.
Subject(s)
Anticonvulsants/administration & dosage , Chemistry, Pharmaceutical/methods , Delayed-Action Preparations/administration & dosage , Epilepsy/drug therapy , Valproic Acid/administration & dosage , Anticonvulsants/adverse effects , Anticonvulsants/blood , Child , Child, Preschool , Delayed-Action Preparations/adverse effects , Female , Humans , Male , Prospective Studies , Valproic Acid/adverse effects , Valproic Acid/bloodABSTRACT
Obesity is a complex multifactorial disease involving genetic and environmental factors and influencing several different metabolic pathways. In this regard, metabonomics, that is the study of complex metabolite profiles in biological samples, may provide a systems approach to understand the global metabolic regulation of the organism in relation to this peculiar pathology. In this pilot study, we have applied a nuclear magnetic resonance (NMR)-based metabolomic approach on urinary samples of morbidly obese subjects. Urine samples of 15 morbidly obese insulin-resistant (body mass index>40; homeostasis assessment model of insulin resistance>3) male patients and 10 age-matched controls were collected, frozen and analyzed by high-resolution (1)H-NMR spectroscopy combined with partial least squares-discriminant analysis. Furthermore, two obese patients who underwent bariatric surgery (biliopancreatic diversion and gastric bypass, respectively) were monitored during the first 3 months after surgery and their urinary metabolic profiles were characterized. NMR-based metabolomic analysis allowed us to identify an obesity-associated metabolic phenotype (metabotype) that differs from that of lean controls. Gut flora-derived metabolites such as hippuric acid, trigonelline, 2-hydroxyisobutyrate and xanthine contributed most to the classification model and were responsible for the discrimination. These preliminary results confirmed that in humans the gut microflora metabolism is strongly linked to the obesity phenotype. Moreover, the typical obese metabotype is lost after weight loss induced by bariatric surgery.
Subject(s)
Insulin Resistance/physiology , Metagenome/physiology , Obesity/microbiology , Obesity/urine , Bariatric Surgery , Blood Glucose/physiology , Body Mass Index , Case-Control Studies , Humans , Intestines/microbiology , Magnetic Resonance Spectroscopy/methods , Male , Metabolomics/methods , Obesity/surgery , Pilot ProjectsABSTRACT
Lesions of the quadriceps muscle (QM) are frequently seen by sonographers, and in most cases they are the result of sports-related trauma. An accurate assessment of the severity of the lesion is essential, particularly when the patient is a professional athlete. In most cases, careful history-taking and a thorough physical examination are sufficient for making the diagnosis and indicating the most suitable imaging studies for each case. Clinical assessment alone, however, may not be sufficient for distinguishing contusions from small, partial tears or for estimating the size of a tear. Therefore, at least in patients who are professional athletes, imaging studies are necessary to plan appropriate therapy that will allow prompt functional recovery. Muscles cannot be visualized with conventional radiography, but it is used routinely in prepubertal patients because it can detect apophyseal detachments, which are the most frequent muscle lesion in this age group. Radiography is also useful when myositis ossificans is suspected. Magnetic resonance imaging, thanks to its excellent tissue contrast, allows simultaneous assessment of muscle, joint, and bone planes. It remains a second-line study due to its high cost and relatively low availability. It is also associated with various contraindications, the most important of which is the presence of a cardiac pacemaker. Ultrasonography has a number of advantages, including widespread availability, absence of contraindications, and low cost. It can also be used for dynamic studies of the muscle during contraction and relaxation, and if doubts arise, scans can easily be obtained of the contralateral muscle for comparison purposes. These qualities make it an excellent tool for follow-up of patients with QM lesions, when follow-up is necessary. This article reviews the anatomy of the QM, the technique used for standard ultrasound examination of this muscle, its normal appearance on ultrasound, and the sonographic characteristics of the most common traumatic lesions that affect it.
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BACKGROUND AND AIMS: Transoral gastroplasty (TOGA) recently emerged as a new, feasible and relatively safe technique for the surgical treatment of obesity. However, so far there are no data on the effects on insulin sensitivity in the literature. Our aim is to evaluate the effect of TOGA on insulin sensitivity and secretion. METHODS AND RESULTS: Nine glucose normo-tolerant obese subjects (age:41+/-6 years; BMI:42.49+/-1.03 kg/m(2)) were studied. Fat-free mass (FM) and fat mass (FM) were assessed by bioelectrical impedance; plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT) before and 3 months after the operation. Insulin sensitivity was calculated using the oral-glucose insulin-sensitivity index, and insulin secretion by C-peptide deconvolution. Three months after surgery, a significant (P=0.008) reduction of BMI to 35.65+/-0.65 kg/m(2), with a decrease of FM and FFM from 57.22+/-2.19 to 41.46+/-3.02 kg (P=0.008) and from 59.52+/-1.36 to 56.67+/-1.10 kg (P=0.048) respectively, was observed. Insulinemia was significantly reduced at fast and at 120 min after OGTT; in contrast, no significant change in glucose concentration was observed. Insulin sensitivity significantly increased (348.45+/-20.08 vs. 421.18+/-20.84 ml/min/m(2), P=0.038) and the incremental area of insulin secretion rate (total ISR) significantly decreased (from 235.05+/-27.50 to 124.77+/-14.50 nmol/min/m(2), P=0.021). Total ISR correlated with weight, BMI and FM (r=0.522, P=0.028; r=0.541, P=0.020; r=0.463, P=0.049, respectively). BMI represented the most powerful predictor of ISR decrease (R(2)=0.541, P=0.020). CONCLUSION: Transoral gastroplasty allows a significant weight loss 3 months after the intervention as well as an amelioration of insulin sensitivity with subsequent reduction of the insulin secretion.
Subject(s)
Gastroplasty/methods , Insulin Resistance , Insulin/metabolism , Obesity/surgery , Adiposity , Adult , Blood Glucose/analysis , Body Composition , Body Mass Index , C-Peptide/blood , Electric Impedance , Energy Intake , Female , Gastroplasty/adverse effects , Glucose Tolerance Test , Humans , Insulin/blood , Insulin Secretion , Male , Middle Aged , Obesity/physiopathology , Treatment Outcome , Weight LossABSTRACT
INTRODUCTION: It is unclear whether the presence of vesicoureteral reflux (VUR) after renal transplantation compromises long-term graft function. The aim of this study in renal allograft recipients with a history of late recurrent urinary tract infections (UTI) was to determine whether the presence of VUR conferred an increased risk of long-term graft dysfunction. METHODS: We included 37 renal allograft recipients, who were at least 2 years after transplantation and had a history of at least 1 recurrent UTI per year underwent voiding cystourethrograms (VCUG). The presence and severity of VUR were graded with severity scores ranging from G1 to G5. RESULTS: Of the 37 patients, 15 (41%) showed low grades of reflux (G1-3) on VCUG. Patient and graft survivals were not significantly different in the VUR group (n = 15) compared with the no VUR group (n = 22) at 1, 3, or 5 years. Renal function assessment by means of serum creatinine (Cr) concentration also demonstrated similar results in both groups at 1, 3, and 5 years: 5 y mean Cr: VUR 1.5 +/- 0.6 mg/dL versus no VUR 1.8 +/- 1.1 mg/dL (P = NS). No difference was also observed in the 2 groups in the number of UTI episodes for each patient per year. CONCLUSIONS: In patients with late UTIs, the presence of low-grade VUR did not affect long-term graft function. There was no indication for a operative repair of low-grade VUR.
Subject(s)
Graft Survival , Kidney Transplantation , Vesico-Ureteral Reflux/complications , Adolescent , Adult , Aged , Allografts , Creatinine/blood , Female , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Transplant Recipients , Young AdultABSTRACT
AIMS/HYPOTHESIS: To aim of the study was to investigate the effect of bilio-pancreatic diversion (BPD) on type 2 diabetes in patients with BMI <35 kg/m(2). METHODS: OGTTs were performed and anthropometric data were compared between five diabetes patients (BMI 27-33 kg/m(2)) following BPD and seven diabetes patients after a low-energy diet. Insulin secretion was computed by C-peptide deconvolution. A euglycaemic-hyperinsulinaemic clamp was performed only in the BPD group and the M value measured. RESULTS: One month after BPD, fasting and 2 h post-OGTT glycaemia decreased from 15.22 +/- 3.22 to 6.22 +/- 0.51 mmol/l (p = 0.043), while insulin sensitivity increased significantly. No significant changes were observed in the low-energy diet group. Insulin secretion did not differ significantly after either intervention. Diabetes amelioration (change in HbA(1c) level) was observed up to 18 months after BPD without pharmacological therapy. CONCLUSIONS/INTERPRETATION: BPD can achieve adequate control of type 2 diabetes also in patients with BMI <35 kg/m(2). The rapid postoperative remission of diabetes is primarily related to an improvement in insulin sensitivity.
Subject(s)
Biliopancreatic Diversion , Diabetes Mellitus, Type 2/surgery , Adult , Blood Glucose/metabolism , Body Composition , Body Mass Index , Diabetes Mellitus, Type 2/diet therapy , Glucose Clamp Technique , Glucose Tolerance Test , Humans , Insulin/metabolism , Middle AgedABSTRACT
AIMS/HYPOTHESIS: We tested the hypothesis that the reversibility of insulin resistance and diabetes observed after biliopancreatic diversion (BPD) is related to changes in circadian rhythms of gastrointestinal hormones. METHODS: Ten morbidly obese participants, five with normal glucose tolerance (NGT) and five with type 2 diabetes, were studied before and within 2 weeks after BPD. Within-day variations in glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP1) levels were assessed using a single cosinor model. Insulin sensitivity was assessed by euglycaemic-hyperinsulinaemic clamp. RESULTS: Basal GLP1 relative amplitude (amplitude/mesor x 100) was 25.82-4.06% in NGT; it increased to 41.38-4.32% after BPD but was unchanged in diabetic patients. GLP1 and GIP mesor were shifted in time after surgery in diabetic patients but not in NGT participants. After BPD, the GLP1 AUC significantly increased from 775 +/- 94 to 846 +/- 161 pmol l(-1) min in NGT, whereas GIP AUC decreased significantly from 1,373 +/- 565 to 513 +/- 186 pmol l(-1) min in diabetic patients. Two-way ANOVA showed a strong influence of BPD on both GIP (p = 0.010) and GLP1 AUCs (p = 0.033), which was potentiated by the presence of diabetes, particularly for GIP (BPD x diabetes, p = 0.003). Insulin sensitivity was markedly improved (p < 0.01) in NGT (from 9.14 +/- 3.63 to 36.04 +/- 8.55 micromol [kg fat-free mass](-1) min(-1)) and diabetic patients (from 9.49 +/- 3.56 to 38.57 +/- 4.62 micromol [kg fat-free mass](-1) min(-1)). CONCLUSIONS/INTERPRETATION: An incretin circadian rhythm was shown for the first time in morbid obesity. The effect of BPD on the 24 h pattern of incretin differed between NGT and diabetic patients. GLP1 secretion impairment was reversed in NGT and could not be overcome by surgery in diabetes. On the other hand, GIP secretion was blunted after the operation only in diabetic patients, suggesting a role in insulin resistance and diabetes.
Subject(s)
Biliopancreatic Diversion , Circadian Rhythm/physiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Gastric Inhibitory Polypeptide/blood , Glucagon-Like Peptide 1/blood , Obesity, Morbid/surgery , Adipose Tissue/anatomy & histology , Adult , Blood Glucose/metabolism , Body Mass Index , Diabetes Mellitus, Type 2/blood , Glucose Tolerance Test , Glycated Hemoglobin/metabolism , Humans , Incretins/blood , Insulin/blood , Insulin Resistance , Middle Aged , Obesity, Morbid/bloodABSTRACT
AIMS/HYPOTHESIS: The aim of this study was to analyse the mechanisms underlying the improvement in glucose tolerance seen in morbidly obese patients undergoing bilio-pancreatic diversion (BPD). SUBJECTS AND METHODS: We evaluated glucose tolerance (by OGTT), insulin sensitivity (euglycaemic-hyperinsulinaemic clamp and the OGTT index OGIS) and beta cell function (OGTT modelling analysis) in 32 morbidly obese (BMI=52+/-7 kg/m(2), mean+/-SD) patients (12 with NGT, 9 with IGT and 11 with type 2 diabetes), before and after BPD, and in 22 lean control subjects. Patients were studied before and from 7 days to 60 months after surgery. RESULTS: BPD improved glucose tolerance in all subjects, who after surgery all had normal glucose tolerance. Insulin sensitivity was restored to normal levels in all subjects (pre-BPD 341+/-79 ml min(-1) m(-2), post-BPD 511+/-57 ml min(-1) m(-2), lean 478+/-49 ml min(-1) m(-2)). The insulin sensitivity change was detectable within 10 days of BPD. At baseline, beta cell sensitivity to glucose was impaired in diabetic subjects (25 [18] pmol min(-1) m(-2) l mmol(-1), median [interquartile range]) compared with lean subjects (82 [98]; p=0.05). After BPD, beta cell glucose sensitivity showed a tendency towards improvement but remained impaired in diabetic subjects (30 [62]; p<0.01 vs lean). Total insulin output decreased in parallel with the insulin sensitivity increase in all groups. In the whole patient group, mean OGTT glucose levels were inversely related to both insulin sensitivity and beta cell glucose sensitivity (r (2)=0.67, partial r=-0.76 and -0.41, respectively). NEFAs, leptin and adiponectin were related to insulin sensitivity but could not explain the early improvement. CONCLUSIONS/INTERPRETATION: Following BPD, glucose tolerance was restored mainly as a result of a rapid and large improvement in insulin sensitivity.
Subject(s)
Biliopancreatic Diversion , Insulin Resistance/physiology , Insulin-Secreting Cells/physiology , Obesity, Morbid/physiopathology , Adiponectin/blood , Adult , Blood Glucose/analysis , Body Mass Index , Body Weight , Fatty Acids, Nonesterified/blood , Female , Glucose Clamp Technique , Glucose Tolerance Test , Humans , Insulin/metabolism , Insulin-Secreting Cells/metabolism , Leptin/blood , Male , Middle Aged , Obesity, Morbid/metabolism , Obesity, Morbid/surgery , Time FactorsABSTRACT
Sirolimus (SRL) in combination with Cyclosporine A (CsA) and steroids has been shown to lower the incidence of acute renal allograft rejection episodes, allowing CsA sparing. We retrospectively compared the incidence of posttransplant diabetes mellitus (PTDM) among kidney transplant recipients (KTx) immunosuppressed with SRL + CsA versus CsA alone. Patients were divided into two groups: SRL + CsA (n = 38) versus CsA (n = 48). Mean follow-up was 53.9 +/- 17.1 months. Seventeen/86 subjects (19.8%) developed diabetes after transplantation (7 IFG, 8.1%; 10 PTDM, 11.6%). The incidence was significantly higher in SRL + CsA (12/38 patients, 31.6%) compared with CsA (5/43 patients, 10.4%) (P = .0144, odds ratio 3.97). More patients required treatment in the SRL + CsA compared to CsA alone cohort (13.2% vs 2.1%, P = .051): 4 pts (10.5%) became insulin- dependent among SRL+CsA, vs none in the CsA group. Use of OHD was similar in both groups (2.6% SRL + CsA vs 2.1% CsA). There were no significant differences between the two groups in terms of age, sex distribution, BMI, or serum creatinine at 1 to 3 and 5 years from transplantation. All PTDM patients are alive at follow-up, while two grafts were lost due to chronic renal allograft dysfunction. Within the limits of a small retrospective study, we observed that SRL in combination with CsA increased the diabetogenic potential of CsA. A possible explanation of our findings is that higher CsA doses were used in the early experience with SRL + CsA; therefore the higher incidence of PTDM that we observed in the SRL + CsA combination may be a sign of toxicity. Careful monitoring of blood levels is mandatory in the SRL + CsA combination to avoid pleiotropic toxicity.
Subject(s)
Cyclosporine/adverse effects , Diabetes Mellitus/epidemiology , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Kidney Transplantation/immunology , Sirolimus/adverse effects , Adult , Drug Therapy, Combination , Female , Humans , Hypoglycemic Agents/therapeutic use , Incidence , Insulin/therapeutic use , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective StudiesABSTRACT
Lymphocele is a complication of renal transplantation, representing a lymphatic collection around the grafted kidney. The use of the immunosuppressive agent sirolimus (SRL) has been associated with a significant increase in lymphocele formation. This complication has been related to the antiproliferative activity of SRL, which delays surgical wound repair and closure of injured lymphatic vessels. The aim of this study was to relate the incidence of lymphocele with immunosuppression among 158 renal transplant patients operated with routine closure of all the visible lymphatic vessels around the iliac vessels and at the renal hilum. The incidence of lymphocele was not significantly different among the various immunosuppressive regimens.
Subject(s)
Kidney Diseases/surgery , Kidney Transplantation/adverse effects , Lymphocele/etiology , Drainage , Humans , Immunosuppressive Agents/adverse effects , Incidence , Lymphocele/epidemiology , Postoperative Complications/epidemiology , Renal Replacement Therapy , Sirolimus/adverse effectsABSTRACT
The hockey-stick surgical incision is becoming more popular than the oblique incision for kidney transplantations. Both incisions are convenient and comfortable. Both have some drawbacks, such as muscle denervation for the former, or section of lateral muscles for the latter. In this retrospective study, we compared these incisions with regard to the incidence of long-term complications, such as postincisional hernia, relaxation of the abdominal wall, and a poor cosmetic result. One hundred patients (50 of each type) were evaluated at an average of 4.5 years after transplantation (3 months-15 years). Occurrence of incisional hernia was 16% in the former (8 cases) versus 4% in the latter (2 cases: X(2) = 4; P < .05). A major relaxation of the abdominal wall was found in 24% of the former (12 cases) versus 8% of the latter (4 cases) (X(2) = 4.76; P < .05). These complications were not correlated with age, sex, weight, side of transplant, or immunosuppressive drugs. In the former patients with hockey-stick incisions, the overall cosmetic results were poor, because in most cases the incision had been prolonged upward, above the transverse umbilical line, even as high as the costal arch. In 20% of the former patients with hockey-stick incisions, the scar had widened, particularly in the upper vertical branch of the J incision. We conclude that the final outcome of the oblique surgical incision was better than the hockey-stick incision because of the lower incidence of hernia and abdominal wall relaxation and the more favorable cosmetic results.
Subject(s)
Kidney Transplantation/methods , Denervation , Female , Follow-Up Studies , Hernia/epidemiology , Hernia/etiology , Humans , Kidney Transplantation/adverse effects , Male , Muscles/innervation , Postoperative Complications/classification , Retrospective Studies , Time FactorsABSTRACT
AIM: Biliopancreatic diversion (BPD) has been accepted as an effective surgical treatment of morbid obesity. The paper presents the results of a personal clinical experience with this procedure, with special focus on the quality of life. METHODS: From January 1, 1992 to June 30, 2002, 122 patients (F/M: 108/14, mean age: 40.2 years, range 21-61) underwent BPD. Mean preoperative body weight was 122.4 kg (range 91-200), with a mean Body Mass Index of 49.1 kg/m2 (range 38-78). Three of these patients were converted from a previous vertical banded gastroplasty to BPD (1 patients with stomach preservation). After at least a 36-month follow-up, 10 patients underwent abdominal dermolipectomy (8 associated to incisional hernia repair, 1 associated to thigh dermolipectomy). RESULTS: Mean postoperative hospital stay was 12 days (range: 11-30). Follow-up is currently in progress in all patients. Weight loss of initial overweight was 75% in 88 patients with a 36-month follow-up, with excellent long-term weight maintenance. Protein deficiency was the main specific complication, encountered in 6 patients (4.9%). Beneficial effects, other than those consequent to weight loss, included permanent normalization of serum cholesterol and glucose without any medication and on a totally free diet. Almost 80% of the patients reported an improvement in their self-esteem, physical activity, work condition and social life. CONCLUSIONS: This clinical experience supports the effectiveness and safety of BPD, despite some criticism. The small number of side effects and complications, the excellent weight loss and the recovery of most co-morbidity leads to a great improvement in quality of life.
Subject(s)
Biliopancreatic Diversion , Obesity, Morbid/surgery , Quality of Life , Weight Loss , Adult , Biliopancreatic Diversion/adverse effects , Body Mass Index , Body Weight , Female , Humans , Male , Middle Aged , Obesity, Morbid/psychology , Protein Deficiency/etiology , Treatment OutcomeABSTRACT
We analysed the action, in rats in vivo, of the protein isoprenylation inhibitor perillyl alcohol (POH) and that of vitamin A, alone or in association, on m-RNA and protein expression of farnesyltransferases (FTases alpha and beta subunits) and their protein substrates RhoA and RhoB, in isolated hepatocytes. Combined administration of POH and vitamin A induced a sharp decrease in FTase alpha protein after 96 h, suggesting an involvement not only of farnesyltransferases but also of geranylgeranyltransferases, which share the FTase alpha protein. FTase beta protein did not decrease. POH plus vitamin A, in contrast with POH or vitamin A alone, induced a decrease in RhoB protein, probably because of different cleavages. No modification was observed in RhoA protein. Vitamin A alone increased RhoB m-RNA and protein expression. As one of the functions of RhoB is cell polarisation, these data support our previous hypothesis of a polarised transport of vitamin A from hepatocytes to hepatic stellate cells. As the behaviours of m-RNAs and proteins in this study were often different, cytoplasmic metabolic pathways must be considered for the parameters studied. The behaviour of Rho B, which is thought to have an antioncogene function, is discussed in view of its isoprenylated forms in the membranes. These preliminary findings stress the need, when studying the association of two isoprenoids in cancer therapy, to consider normal as well as tumour-bearing animals.
Subject(s)
Alkyl and Aryl Transferases/metabolism , Hepatocytes/metabolism , Liver/metabolism , Monoterpenes/pharmacology , RNA, Messenger/metabolism , Vitamin A/pharmacology , rhoA GTP-Binding Protein/metabolism , rhoB GTP-Binding Protein/metabolism , Animals , Liver/cytology , Male , Monoterpenes/metabolism , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Vitamin A/metabolismABSTRACT
UNLABELLED: End-stage renal disease is associated with disorders in hypothalamic-pituitary-gonadal function. Immunosuppressive therapies may influence the restoration of normal levels of gonadal hormones after renal transplantation. The aim of the present study was to evaluate the hormonal status of successful renal transplant recipients who were treated with different immunosuppressive agents. METHODS: Testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured in 59 male renal transplant recipients with stable graft function with serum creatinine <2.5 mg/dL. Patients were treated with three different immunosuppressive regimens: group I, calcineurin inhibitors (CI; n = 15), group II, sirolimus without calcineurin inhibitors (SRL; n = 15), group III, sirolimus in combination with calcineurin inhibitors (SRL * CI; n = 29). RESULTS: Testosterone was significantly lower in group II versus group I (3.12 +/- 1.23 versus 4.39 +/- 1.53 ng/mL; P < .0197). Group III had higher testosterone values than group II, but lower than group I. FSH and LH were also higher in the SRL group, but the differences were not statistically significant, perhaps because of the small number of patients. No relationship was found between testosterone blood levels and age, posttransplant follow-up, renal function, time on dialysis, body mass index, steroid use, or posttransplant diabetes. CONCLUSION: Sirolimus seems to impair the improvement of gonadal function after renal transplantation. Further prospective studies are needed to confirm these data before patients are advised of this potential side effect.
Subject(s)
Follicle Stimulating Hormone/blood , Immunosuppressive Agents/adverse effects , Kidney Transplantation/physiology , Luteinizing Hormone/blood , Sirolimus/adverse effects , Testosterone/blood , Creatinine/blood , Follow-Up Studies , Humans , Kidney Transplantation/immunology , Male , Middle Aged , Regression Analysis , Time FactorsABSTRACT
We report two kidney transplant recipients who developed severe limb lymphedema under sirolimus (SRL) immunosuppression. The patients received SRL 10 and 2 mg/d to achieve target levels of 10 to 20 ng/mL with tapering doses of prednisone. Renal function and drug levels were monitored monthly. Patient 1 developed lymphedema of the left upper limb 3 years posttransplantation, after having been exposed to high SRL doses in the preceding 2 years (mean SRL dose-9.5 mg/d, mean trough level-26.3 ng/mL, mean serum creatinine-1.63 mg/dL). In patient 2 lymphedema of both upper and lower right limbs occurred 18 months posttransplantation (mean SRL dose-3.2 mg/d, mean trough level-8.8 ng/mL, mean serum creatinine-2.9 mg/dL). Hypercholesterolemia and hypertriglyceridemia were also observed in both patients before SRL reduction/conversion. No signs of hematopoietic toxicity were observed. In both patients magnetic resonance (MR) angiography of the limb was negative for vascular obstruction, and lymphoscintigraphy revealed lymphatic obstruction. In patient 1 lymphedema improved significantly following SRL reduction and lymphatic drainage massage therapy. Patient 2 was converted to cyclosporine (CsA) improving markedly after conversion. Hypercholesterolemia and hypertriglyceridemia also improved significantly in both patients after reduction/conversion. We conclude that SRL may facilitate the occurrence of lymphatic obstruction by mechanisms that are presently unexplained. Lymphedema of the limbs in renal transplant recipients under SRL treatment, especially if on the same side as the hemodialysis access, should warn the transplant physician to rapidly reduce or withdraw SRL before the occurrence of complete obstruction.
Subject(s)
Arm , Kidney Transplantation/immunology , Leg , Lymphedema/chemically induced , Sirolimus/adverse effects , Adult , Female , Humans , Immunosuppressive Agents/adverse effects , Lymphedema/diagnosis , Magnetic Resonance Imaging , Male , Middle Aged , Wound Healing/drug effectsABSTRACT
This open-label, phase 3b, extension trial in renal transplant recipients (Sirolimus Study 311) assessed the long-term safety of sirolimus (SRL) administered with cyclosporine (CsA) (SRL + CsA group, n = 98) or without CsA (SRL group, n = 69). Renal transplant recipients who had either completed one of seven previous SRL studies sponsored by Wyeth Research or had participated for > or =3 months and reached a protocol-designated endpoint were eligible for enrollment. Data were available for 167 patients, all of whom initially received steroids. Mean total SRL exposure was 1526 days, including previous study participation. After enrollment in the extension study, there were significantly more acute rejections in the SRL + CsA group (6.1% vs 0%, P < .05). Differences in rates of graft loss (3.1% vs 1.4%) and death (6.1% vs 1.4%) were not significantly different between SRL + CsA and SRL groups, respectively. At 48 months after transplantation, calculated GFR (53.4 vs 70.9 mL/min) and hemoglobin (124.9 vs 136.6 g/L) were significantly better in the SRL group. Lipid values were not significantly different between groups at 48 months. The incidence of treatment-emergent increased creatinine, anemia, hypertension, headache, epistaxis, abnormal kidney function, and upper respiratory infection were significantly higher in the SRL + CsA group, whereas no adverse events were significantly higher in the SRL group. Malignancies were reported more frequently (11.2% vs 0%) with SRL + CsA. Results from this extension study indicate that SRL-based therapy without CsA is a safe alternative to combination therapy with CsA, offering long-term improvement in renal function with no increased risk of late acute rejection.
Subject(s)
Cyclosporine/therapeutic use , Kidney Transplantation/physiology , Sirolimus/therapeutic use , Adult , Creatinine/blood , Drug Therapy, Combination , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/epidemiology , Histocompatibility Testing , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Kidney Transplantation/mortality , Male , Survival Analysis , Time Factors , Tissue DonorsABSTRACT
AIM: To determine the concentration of insulin-like growth factor-I (IGF-I) in exclusively breast-fed (BF) and formula-fed (FF) infants in the first 5 months of life and to study the relationship between the IGF-I level and Z score for weight, body mass index (BMI) and tricipital skin-fold thickness. METHODS: We performed a cross-sectional study in order to evaluate serum IGF-I in 97 age-matched healthy term infants: 50 FF and 47 BF. RESULTS: FF infants showed higher values of IGF-I (38.9 +/- 12 ng/ml) when compared to BF infants (26.7 +/- 11.6 ng/ml; p < 0.05). A positive correlation was found between IGF-I values and Z score for weight (p < 0.001), BMI (p = 0.014), tricipital skin-fold thickness (p = 0.043) and age (p = 0.02). CONCLUSION: These results show that the IGF-I serum concentration is higher in FF infants. The observed association between IGF-I and Z score for weight, BMI, tricipital skin-fold thickness confirms the effect of different infant feeding on body size.
Subject(s)
Body Mass Index , Body Weight/physiology , Breast Feeding/statistics & numerical data , Infant Formula/statistics & numerical data , Insulin-Like Growth Factor I/metabolism , Skinfold Thickness , Analysis of Variance , Arm/physiology , Cross-Sectional Studies , Female , Humans , Infant , Infant Formula/administration & dosage , Infant, Newborn , Male , Reference ValuesABSTRACT
BACKGROUND: Leptin is a hormone present in breast milk, which regulates food intake and energy metabolism. AIM: To investigate whether leptin levels are different in breast-fed (BF) or formula-fed (FF) infants in the first months of life. METHODS: We evaluated serum leptin by radio-immunoassay and anthropometric parameters in 51 infants at the average age of 62.8+/-30 days, 25 exclusively BF and 26 exclusively FF. RESULTS: Leptin serum values were higher in BF (7.1+/-10.4 ng/ml) than in FF (3.7+/-3.87 ng/ml) infants (p <0.05). Leptin values were higher in females (6.9+/-9.87 ng/ml) than in males (3.5+/-3.88 ng/ml) (p <0.05). No differences were found in anthropometric measurements and body mass index. CONCLUSION: The kind of feeding might be a factor affecting serum leptin concentration in term infants. The long-term consequences of this difference between BF and FF infants and leptin's role in promoting obesity later in life are unknown.