| 1. |
- Mancini, M. C., et al.
(författare)
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Effect of gastric bypass on spontaneous growth hormone and ghrelin release profiles
- 2006
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Ingår i: Obesity (Silver Spring). ; 14:3, s. 383-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to analyze growth hormone (GH) concentrations in obese women before and after Roux-en-Y gastric bypass (RYGBP) and how resulting changes in weight, fat mass, ghrelin levels, and insulin sensitivity affect GH secretion. RESEARCH METHODS AND PROCEDURES: Blood was sampled at 20-minute intervals for 24 hours in 10 non-diabetic premenopausal severely obese women before and 6 months after RYGBP. GH concentrations were measured in all samples, and serum ghrelin was collected at five time-points. RESULTS: After a 27% BMI drop (55.9 +/- 6.2 to 40.7 +/- 5.8 kg/m(2)), blunted GH profiles underwent partial recovery. Basal, postprandial, and mean ghrelin concentrations were not changed. A negative correlation was found between mean GH levels and insulin and homeostasis model assessment (p < 0.01). BMI accounted for 54% of GH variation. DISCUSSION: Partial recovery of GH secretion after RYGBP-induced weight loss suggests that a blunted secretion is not a causal factor of obesity but a consequence of the obese state and does not seem to be ghrelin-level dependent.
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| 2. |
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| 3. |
- Craig, M. E., et al.
(författare)
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Growth hormone treatment and adverse events in Prader-Willi syndrome: data from KIGS (the Pfizer International Growth Database)
- 2006
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Ingår i: Clin Endocrinol (Oxf). ; 65:2, s. 178-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the response to recombinant GH treatment and adverse events in children with Prader-Willi syndrome (PWS) from KIGS, the Pfizer International Growth Database. PATIENTS: A total of 328 children (274 prepubertal, median age 6.0 years; 54 pubertal, median age 12.7 years) were treated for 1 year and 161 children were treated for 2 years with GH. RESULTS: Height standard deviation score (SDS) increased significantly during treatment; the response was greater in prepubertal (-0.7 vs.-1.8 pretreatment) compared with pubertal children (-1.5 vs.-1.8). Predictors of first-year height velocity in multiple regression analysis were GH dose, body weight (positively correlated), height SDS minus mid-parental height SDS and chronological age (negatively correlated), together accounting for 39% of the variation in response to GH. Body mass index (BMI) SDS did not change significantly during 2 years of treatment. Of all the 675 GH-treated PWS patients in KIGS, there were five cases of sudden death (age range 3-15 years). Three were obese (weight for height > 200%) and causes of death included bronchopneumonia, respiratory insufficiency and sleep apnoea. Scoliosis was the most commonly reported adverse event (n = 24), four children developed hyperglycaemia and six had presumptive diabetes (type 2 in five, and one case of type 1). CONCLUSIONS: Short-term growth improved in response to conventional doses of GH in children with PWS. Prior to commencement of GH, examination of the upper airways and sleep studies should be performed in PWS patients. GH should be used with caution in those with extreme obesity or disordered breathing and all patients should be closely monitored for adverse events.
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| 4. |
- Glimelius, Bengt, et al.
(författare)
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Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group
- 2005
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Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 904-12
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Tidskriftsartikel (refereegranskat)abstract
- Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to+/-levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations.
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| 5. |
- Isaksson, B, et al.
(författare)
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Chronically administered islet amyloid polypeptide in rats serves as an adiposity inhibitor and regulates energy homeostasis
- 2005
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 5:1, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- Aims/Hypothesis: Islet amyloid polypeptide ( IAPP) reduces food intake and body weight in laboratory animals. In addition, IAPP appears to regulate nutrient metabolism. In the present studies, we investigated the effect of chronic IAPP treatment on different aspects of energy homeostasis. Methods: IAPP was infused ( 25 pmol/kg/min) from subcutaneous osmotic pumps for 2 - 7 days. Rats in 2 saline-infused control groups were fed ad libitum (AF) or pair-fed (PF) against the IAPP-treated rats. Results: As expected, the IAPP infusion reduced food intake and body weight gain. In addition, the IAPP treatment decreased the epididymal fat pad ( vs. PF rats, p < 0.05) and lowered circulating levels of triglycerides (vs. PF rats, p < 0.05), free fatty acids ( vs. PF rats, p < 0.05), leptin ( vs. both AF and PF rats, p < 0.05) and insulin ( vs. AF rats, p < 0.05). In contrast, glucose and protein metabolism in the IAPP-treated rats was largely unchanged, as shown in results regarding serum glucose, glucose transport in skeletal muscle, blood urea nitrogen, and glycogen and protein content in the liver and in skeletal muscle. Conclusion/Interpretation: In summary, chronic IAPP exposure led to a changed lipid metabolism, which was characterized by decreased adiposity, hypolipidemia and hypoleptinemia, and to unchanged glucose and protein homeostasis. These results were similar to those seen in rodents during chronic exposure to another satiety/adiposity regulator, leptin. In conclusion, chronically administered IAPP plays a role as a satiety and adiposity signal in rats, and helps regulate energy homeostasis.
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| 6. |
- Lindblad, M. S., et al.
(författare)
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Biodegradable polymers from renewable sources : Rheological characterization of hemicellulose-based hydrogels
- 2005
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 6:2, s. 684-690
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Tidskriftsartikel (refereegranskat)abstract
- Hemicellulose-based hydrogels were prepared by radical polymerization of 2-hydroxyethyl methacrylate or poly(ethylene glycol) dimethacrylate with oligomeric hydrosoluble hemicellulose modified with well-defined amounts of methacrylic functions. The polymerization reaction was carried out in water at 40 degrees C using a redox initiator system. The hydrogels were in general elastic, soft, and easily swellable in water. Their viscoelastic properties were determined by oscillatory shear measurements on 2 mm thick hydrogels under a slight compression to avoid slip, over the frequency range 10(-1) to 10(2). The rheological characterization indicated that the elastic response of the hydrogels was stronger than the viscous response, leading to the conclusion that the hydrogel systems displayed a predominantly solidlike behavior. The curves showed an increase in shear storage modulus with increasing cross-linking density. The nature of the synthetic comonomer in the hemicellulose-based hydrogels also influenced the shear storage modulus. Comparison of hemicellulose-based hydrogels with pure poly(2-hydroxyethyl methacrylate) hydrogels showed that their behaviors were rather similar, demonstrating that the synthetic procedure made it possible to prepare hemicellulose-based hydrogels with properties similar to those of pure poly(2-hydroxyethyl methacrylate) hydrogels.
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| 7. |
- Ranke, M. B., et al.
(författare)
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Major determinants of height development in Turner syndrome (TS) patients treated with GH: analysis of 987 patients from KIGS
- 2007
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Ingår i: Pediatr Res. - : Springer Science and Business Media LLC. - 0031-3998. ; 61:1, s. 105-10
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about factors determining height outcome during GH treatment in Turner syndrome (TS). We investigated 987 TS children within the Kabi International Growth Study (KIGS) who had reached near adult height (NAH) after >4 y GH treatment (including >1 y before puberty). Through multiple regression analysis we developed a model for NAH and total gain. Our results were as follows (median): 1) At start, age 9.7 yrs, height (HT) 118.0 cm (0.0 TS SDS), projected adult height 146.1 cm, GH dose 0.27 mg/kg wk; 2) NAH HT 151.0 cm (1.5 TS SDS); 3) Prepubertal gain 21.2 cm (1.6 TS SDS); 4) Pubertal gain 9.4 cm (0.0 TS SDS). NAH correlated (r = 0.67) with (ranked) HT at GH start (+), 1 year responsiveness to GH (+), MPH (+), age at puberty onset (+), age at GH start (-), and dose (+). The same factors explained (R = 0.90) the total HT gain. However, HT at GH start correlated negatively. Karyotype had no influence on outcome. Evidently, height at GH start (the taller, the better), age at GH start (the younger, the better), the responsiveness to GH (the higher, the better) and age at puberty (the later, the better) determine NAH.
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| 8. |
- Valuniene, M., et al.
(författare)
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Leptin levels at birth and in early postnatal life in small- and appropriate-for-gestational-age infants
- 2007
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Ingår i: Medicina (Kaunas). - 1648-9144. ; 43:10, s. 784-791
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate leptin concentration at birth and in early postnatal life in small- and appropriate-for-gestational-age infants and to assess its relationship with infants' anthropometry at birth and some characteristics of maternal pregnancy. MATERIALS AND METHODS. A total of 367 infants born after 32-42 weeks of gestation were enrolled in the study. Umbilical cord blood samples were collected from 80 small- and 287 appropriate-for-gestational-age newborns. Altogether, 166 venous blood samples were taken from these neonates on days 2-6 of life. RESULTS. Cord leptin levels were significantly lower in small- compared to appropriate-for-gestational-age infants. We observed a positive correlation between cord leptin and birth weight, all neonatal anthropometric parameters, placental weight, and some maternal nutritional factors. In multivariate analysis, cord leptin concentration explained up to 15% of the variation in sum of newborn's skinfold thickness but only 5% of the variation in birth weight. Postnatally, leptin concentration decreased markedly to the similar low levels in both infant groups and remained so during the first postnatal week. CONCLUSIONS. Significantly lower cord leptin concentration in small-for-gestational-age neonates reflects a lower fat mass content compared to appropriate-for-gestational-age infants. However, an abrupt decrease in leptin levels shortly after birth in both groups suggests that placenta could be an important source of leptin in fetal circulation. The impact of low leptin levels at birth in small-for-gestational-age infants on their postnatal appetite and weight gain remains to be elucidated in future studies.
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| 9. |
- Yang, Q., et al.
(författare)
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Morphological appearance, content of extracellular matrix and vascular density of lung metastases predicts permissiveness to infiltration by adoptively transferred natural killer and T cells.
- 2006
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Ingår i: Cancer immunology, immunotherapy : CII. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 55:6, s. 699-707
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Tidskriftsartikel (refereegranskat)abstract
- We have recently shown that adoptively transferred, IL-2-activated natural killer (A-NK) cells are able to eliminate well-established B16-F10.P1 melanoma lung metastases. However, some B16-F10.P1 lung metastases were resistant to infiltration by the A-NK cells and also resistant to the A-NK cell treatment. The infiltration-resistant (I-R) B16-F10.P1 metastases had a unique "compact" morphology compared to the "loose" morphology of the infiltration-permissive (I-P) metastases. Here, we show that I-P loose tumors and I-R compact tumors are also found in lung metastases of mouse Lewis lung carcinoma (3LL), MCA-102 sarcoma, and MC38 colon carcinoma as well as rat MADB106 mammary carcinoma origin. Furthermore, the infiltration resistance of the compact tumors is not restricted to A-NK cells, since PHA and IL-2 stimulated CD8+ T-cells (T-LAK cells) also infiltrated the compact tumors poorly. Analyses of tumors for extracellular matrix (ECM) components and PECAM-1(+) vasculature, revealed that the I-R lesions are hypovascularized and contain very little laminin, collagen and fibronectin. In contrast, the I-P loose tumors are well-vascularized and they contain high amounts of ECM components. Interestingly, the distribution pattern of ECM components in the I-P loose tumors is almost identical to that of the normal lung tissue, indicating that these tumors develop around the alveolar walls which provide the loose tumors with both a supporting tissue and a rich blood supply. In conclusion, tumor infiltration by activated NK and T cells correlates with the presence of ECM components and PECAM-1(+) vasculature in the malignant tissue. Thus, analysis of the distribution of ECM and vasculature in tumor biopsies may help select patients most likely to benefit from cellular adoptive immunotherapy.
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