| 1. |
- Abdiu, Avni, 1963-
(författare)
-
Growth regulation in sarcomas : studies in vivo and in cell culture
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sarcomas are malignant tumors of mesenchymal origin, and can arise in soft-tissue and in bones. It has been suggested that the abnormal growth regulation in sarcoma cells may be due to an autocrine mechanism, in which the cells are stimulated by an endogenous production of growth factors. Platelet-derived growth factor (PDGF) has been detected in sarcomas, and may be one of the growth factors important for sarcoma growth.PDGF, originally discovered in platelets, is produced by, and binds to, a variety of cells. PDGF plays several roles both in normal conditions and in disease.Suramin is a polyanionic drug with antineoplastic activities, and is known to dissociate growth factors from their receptors. Suramin has been shown to inhibit growth in several tumors and tumor cell lines; however, some tumor cells have been unaffected, or even stimulated, by suramin.The present work was performed in order to a) examine the effects of suramin on sarcoma growth in vivo; b) investigate the kinetics of extravascularly administered PDGF in vivo; c) establish and characterize human sarcoma cells in vitro, including their relation to PDGF; d) evaluate the effects of suramin on sarcoma growth in vitro; e) compare the effects of PDGF on sarcoma growth in vivo and in vitro.Suramin was shown to inhibit growth of two different human osteosarcoma xenografts grown in nude mice. The action is believed to be mainly cytostatic, as the tumors continued to grow, albeit at a lower pace: the tumors of the suramin treated mice had a volume of one-third or less than the untreated ones. The percentage of cells in S and G2-M cell cycle phases was increased by suramin treatment, suggesting a selective effect of the drug in the S and G2 period.Blood and serum levels of 125I, after extravascular administration of 125I-PDGF-AB by intraperitoneal, intramuscular or subcutaneous injection in mice, were found to rise to a maximum 2-4 hours after injection. The levels of radioactivity persisted over several hours. Precipitiation of serum with 10% trichloracetic acid revealed that more than 50% of the radioactivity was in a macromolecular form. Gel chromatography of the serum showed that a major portion of the radioactive material in the circulation had the same molecular size as the original 125I-PDGF-AB.Eight cell lines derived from malignant fibrous histiocytomas (MFH) were established and characterized. A heterogeneity in the morphology of the MFH cell lines was noted. This heterogeneity was also reflected in the expression of mRNA for PDGF, transforming growth factor-alpha (TGF-/alpha/) and their receptors, ability to grow in serumfree media and secretion of PDGF into growth media. Two cell lines, able to grow in serum-free medium, coexpressed MRNA for PDGF, TGF-/aplpha/ and their receptors, suggesting that they may be regulated in an autocrine manner. However, other cell lines, unable to grow in a serum-free medium, also displayed this coexpression of mRNA. The simultaneous expression of a growth factor and its receptor is therefore not generally indicative of an autocrine mechanism.All cell lines, unable to grow in a serum-free medium, were growth inhibited by high-dose suramin (200 ug/ml). The two cell lines, previously noted to grow under serum-free conditions, were not affected by the high-dose suramin treatment. The finding that only serum-dependent human MFH cell lines were inhibited by high doses of suramin indicates that serum dependence in vitro may predict sensitivity of sarcoma cells to suramin.Two human sarcoma xenografts, one osteosarcoma and one malignant fibrous histiocytoma, were treated with human PDGF-AB when grown in nude mice. No effects on tumor growth were noted, although immunohistochemical studies revealed an expression of PDGF receptors. Furthermore, both sarcomas were markedly stimulated by PDGF-AB in vitro. It is concluded that mechanisms or factors other than available PDGF were limiting the growth of the examined tumors in vivo.
|
|
| 2. |
- Andersson, Kerstin
(författare)
-
Inhibition of phagocyte signaling by the Yersinia virulence protein YopH
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Yersinia pseudotuberculosis evades the immediate immune defense of a host organism by inhibiting bactericidal functions of phagocytes, including phagocytosis, cytokine release, and the oxidative burst. Consequently, this pathogen can survive and multiply in lymphatic tissues. An ensemble of proteins called Yops are involved in the virulence of Y. pseudotuberculosis. Through a polarized mechanism, certain Yops are translocated directly into the host cell, where they are assumed to exert their effects. The present studies were performed to gain further knowledge about the role of the tyrosine phosphatase YopH in Yersinia virulence, especially in regard to effects on the immediate functions and signals of phagocytes.Y. pseudotuberculosis was found to resist phagocytic uptake by a mechanism involving translocation of bacterially synthesized YopH into the target cell. The antiphagocytic mechanism had an impact on ingestion of both non-opsonized and IgO-opsonized bacteria. Phagocytosis of a YopH-negative strain was accompanied by induction of tyrosinephosphorylated cellular proteins (among them paxillin), and this involved binding of the bacterial surface protein invasin to ß1 integrins of the eukaryotic cell, which also initiated an immediate Ca2+ signal in the target cell. The phosphotyrosine proteins Cas and FYB were recruited to the focal complex area during phagocytosis of the YopH-negative strain. Furthermore, we found that a phosphatase-inactive YopH eo-localized with focal adhesion to the periphery of a host cell. In phagocytes infected with wild-type bacteria, phosphatase-active YopH dephosphorylated Cas and FYB, which caused disruption of focal complex structures, and inhibition of the Ca2+ signal. The phosphorylation events as well as the Ca2+ signal were rapid responses to bacterial attachment, suggesting that the action of YopH is instantaneous.Genetic studies revealed that the YopH protein contain an inherent sequence important for anchoring at focal complex structures. Specifically, deletion of the amino acids 223-226 disabled YopH to localize to the focal complexes and to inhibit phagocytosis and Ca2+-signaling. This indicates that Y opH must bind to a specific site in focal complexes to focus its activity on the appropriate substrates (i.e. Cas and FYB). Our results show that targeting such complexes is important for Y. pseudotuberculosis, not only as a means of avoiding ingestion by phagocytes, but also for its virulence in mice.
|
|
| 3. |
- Blom, René
(författare)
-
Sarcoma of the female genital tract : Histopathology, DNA cytometry, p53 and mdm-2 analysis related to prognosis
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sarcomas of the female genital tract are rare tumors and account for less than 5% of gynecologic malignancies. Traditionally, gynecologic sarcomas have been divided into different tumor types according to their histopathological features. The most common are leiomyosarcoma (LMS), malignant mixed Müllerian tumors (MMMT), endometrial stromal sarcoma (ESS) and (Müllerian) adenosarcoma. The different tumor types are highly aggressive with early lymphatic and/or hematogenous spread. Treatment is difficult and it is believed that sarcomas have a low radio-and chemosensitivity, and the mainstay in treatment is surgical removal of the tumor. The most important prognostic feature has been tumor stage. Nevertheless, there are some early-stage tumors that run a biological course different from that expected and additional prognostic factors indicating high-risk tumors are desirable.The study cohort consists of 49 uterine LMS, 44 uterine MMMTs, 17 uterine ESS, 11 uterine adenosarcomas and 26 ovarian MMMTs. The tumors were analyzed in a retrospective manner for DNA ploidy, S-phase fraction (SPF), p53 and mdm-2 expression, as well as traditional clinical and pathological prognostic factors, such as tumor stage. grade, atypia and mitotic index.Of the 49 LMS, 36 (86%) were non-diploid and 13 (27%) were p53-positive. Among the 44 uterine MMMTs, 30 (68%) were non-diploid and 27 (61%) had an SPF>10%. Twenty-seven (61%) overexpressed p53 and 11 (25%) were mdm-2 positive. Furthermore, 40 (91%) of the uterine MMMTs had a high mitotic count and 42 (95%) had high grade cytologic atypia. All low-grade ESS were DNA diploid and had a low SPF. Among the four high-grade ESS, three (75%) were DNA aneuploid and three (75%) were p53-positive. Among 1 1 adenosarcomas, eight (73%) were non-diploid. All ovarian MMMTs were non-diploid and all but two had an SPF>10%. 19 (73%) ovarian MMMTs were p53positive.The 5-year survival rate was 33% for LMS, 38% for uterine MMMT, 57% for ESS, 69% for adenosarcoma and 30% for ovarian MMMT.Thirty-five (71%) patients with LMS died of disease and two of intercurrent disease. Stage was found to be the most important factor for survival (p=0.007); in addition DNA ploidy (p=0.045) and SPF (p=0.041) had prognostic significance.Twenty-seven (61%) patients with uterine MMMT died of disease and six (14%) died of intercurrent disease. Stage was the only prognostic factor for survival.Nine (53%) patients with ESS died of disease. There was a significant correlation of survival to tumor grade (p=0.007), DNA ploidy (p=0.026), SPF (p=0.048) and stage (p=0.026).Of the 11 patients with adenosarcoma, four (36%) patients died of disease and three (27%) patients died of intercurrent disease. There were no variables that correlated with survival.Eighteen (69%) patients with ovarian MMMT died of disease and two (8%) patients died of intercurrent disease. In a multivariate analysis, only stage reached independent prognostic significance for survival (p=0.023).In summary, stage represents the most important prognostic factor for survival for uterine and ovarian sarcomas. DNA flow cytometry is useful in gaining additional prognostic information for LMS and ESS. P53-and mdm-2 overexpression had no prognostic value for survival rate. Most of the MMMT overexpressed p53 and were non-diploid. Treatment of sarcomatous neoplasms is difficult and the mainstay remains surgical removal of the tumor. For patients with early stage sarcoma there was a high recurrence rate, which suggests that a large proportion of patients may have systemic micrometastasic disease at the time of diagnosis. Recurrent and metastatic uterine sarcoma remains an incurable disease, and treatment must be considered palliative.
|
|
| 4. |
- Bojestig, Mats
(författare)
-
Glycaemic Control and Complications in Type 1 Diabetes
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There have been substantial changes in the management of diabetes since the 1960' s.We studied all 213 patients in our catchment area in whom Type I diabetes was diagnosed before the age of 15 years between 1961 and 1980, 92% were followed from the onset of diabetes to 1991 or to the time of deathThe cumulative incidence of diabetic nephropathy has decreased substantially in recent decades from 30% to 9% after 25 year's diabetes duration, probably as a result of improved glycaemic control. Neither the cumulative incidence of severe retinopathy nor hypertension (140/90mmHg) changed during the last decades.The risk to develop severe retinopathy or nephropathy was higher in patients with Very Poor glycaemic control (HbA1c;::.8.4%) vs. patients with Poor control (HbA1c ~ 7 .2<8.4% )(p<0.001). Patients with Poor control had an increased risk to develop severe retinopathy vs. patients with Good control (HbA1c<7 .2% )(p<0.008) but there was no difference in the risk for nephropathy. No patients with Good control developed nephropathy and only one patient developed severe retinopathy during 25 years of diabetes. Up to a diabetes duration of 25 years both diabetic nephropathy and severe retinopathy can be avoided but the degree of glycaemic control needed for prevention differs.The course of microalbuminuria during the 1980's was studied with a 10-year follow up of 109 Type 1 diabetes patients. Only 5 (19%) of the initially micro-albuminuric patients developed macro-albuminuria during the 10 year follow up period and 15 (58%) patients decreased their AER to normal. The initially micro-albuminuric patients, who normalised their AERimproved their glycemic control. In the majority of patients with micro-albuminuria in whom it is possible to obtain a good glycemic control, micro-albuminuria will disappear and the risk of developing nephropathy is markedly reduced.PRA and All concentrations were significantly lower in Type 1 diabetic patients (n=80) than in matched healthy controls (n=75). ANP levels were higher in patients than in controls. In the patients PRA correlated negatively to the mean value of HbA1c during the previous five years. Patients with Type 1 diabetes, specially those with very poor glycaemic control, have a suppressed RAS and increased ANP levels.
|
|
| 5. |
- Cao, Jun
(författare)
-
Characterization of antibodies against Helicobacter pylori
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- H. pylori is associated with the development of peptic ulcer, gastritis, and gastric cancer. Eradication of H. pylori by antibiotic treatment gives a healing of peptic ulcer and gastritis. However, due to drug resistance, there is a great need to explore alternative ways to eliminate bacterial infections.The goals of the present study were to characterize MAbs against surface components of H. pylori, and to investigate the functions of the bacterial surface components.Murine MAbs against surface components of H. pylori were produced by immunization of mice followed by hybridoma formation. One of the MAbs of the IgG1 subclass, was specific for both the spiral and coccoid forms of H. pylori. It reacted with a 28 kDa protein that was present in all the 5 strains of H. pylori tested. The MAb based indirect immunofluorescence microscopy on formalinfixed antral and corpus biopsy specimens from H. pylori associated gastritis patients showed that 9 of 9 antral and 5 of 6 corpus specimens harbored the coccoid form of H. pylori.An ScFv-phage which was derived from an M13 phage and mRNA of hybridomas secreting H. pylori MAbs, reacted with a 30 kDa H. pylori surface antigen. By means of immunofluorescence microscopy the phage was shown to bind to both the spiral and coccoid forms of the bacterium. In vitro the recombinant phage exhibited a bacteriocidal effect. When H. pylori was pretreated with the phage before oral inoculation of mice, the colonization of the mouse stomachs by the bacterium was significantly reduced. The parental MAbs were of the IgG1 subclass. The antigen was identified as a urease associated 30 kDa protein. The MAb decreased viability of the spiral form in broth culture, and reduced intracellular ATP in both spiral and coccoid forms of H. pylori.One MAb, 5D6 of the IgG2a subclass, was specific to a 56 kDa H. pylori protein. Immunofluorescence microscopy showed that this protein was located on the surface of both the spiral and coccoid forms of H. pylori. The MAb also bound to cells of the basal third of the oxyntic mucosa of rat stomachs and these cells were identified as gastric ECL cells. Sera of H. pylori-positive patients were investigated for ECL cell (auto)antibodies by means of ELISA using purified rat ECL cells as antigen. Ten (25%) of 40 sera from patients with atrophic corpus predominant gastritis scored positive; 2 (8%) of 26 sera from the patients with duodenal ulcer scored positive; only 1 serum (6%) from 16 healthy subjects was slightly positive. Four positive clones were obtained from a DNA hybridization of H. pylori and human gastric mucosa.The present results show that the MAb based immunochemistry provides a rapid and specific detection of both the spiral and coccoid forms. Binding of a urease associated 30 kDa protein by an ScFv-phage, or by its parental MAbs, decreased the viability of H. pylori. The protein may be considered as a candidate for a future vaccine. An antigenic mimicry which was found in surface of H. pylori and gastric ECL cells suggests a pathogenic role in gastritis.
|
|
| 6. |
- Chatziarsenis, Marios
(författare)
-
New policies at Nosokomio Neapolis : introducing small areas research and development in a Cretan primary/hospital care setting
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present thesis gives an account of the scheduled transformation of a combined Hospital and Primary Health Care institution, Nosokomio Neapolis, in a semi-rural community on Crete to an integrated population health research and development (R&D) centre by relatively minor organisational updatings and focused scientific studies with academic and political support and supervision. This process has engaged the whole local team, and the thesis is concerned with some of its bearing "Ariadne threads". First, the health systems perspective and framework of the Nosokomio Neapolis are described, including opportunities and scope of the directed, needs-and-outcome-oriented R&D undertaken also outside the focus of the present thesis, e.g. osteoporosis, cardiovascular diseases and accidents (I).Then, and new to Greece, three different and complementary lines are drawn concerning primary health care (PHC) quality assurance research in the three ages and with an epidemiological, risk factor and staff emphasis, respectively. The first of them is the primary prevention sector of immunisation in Cretan schoolchildren, where insufficient levels were found and measures of improvement implemented (II). The second concerns the determination of hepatitis A, B, and C markers and assessment of immunisation status in the Neapolis prison inmates and staff, and showing that both are high risk groups, where secondary and tertiary preventive measures are highly warranted (III). In the third age, research focused upon staff capacity regarding PHC physicians' level of knowledge and patterns of practices related to dementia in two European Regions; Crete, Greece and OstergOtland, Sweden. This is predominantly a tertiary preventive sector, where the care organisation is instrumentaL The study showed in the younger Greek PHC physicians a need for quality improvement, in particular in relation to Alzheimer's disease (IV).The final, fifth and sixth papers give an overview of the decisive step out to society, by a specially designed questionnaire, in order to achieve community involvement: a vital requirement for population participation and shar-ingjn the decentralised work towards Health For All by year 2000 and beyond (V - VI). The general conclusion of the thesis is that the new policies of small-areas action R&D in the community are both needed and relevant in the primary health care of Cretan and other Mediterranean areas.
|
|
| 7. |
- Dimberg, Jan
(författare)
-
Studies on expression and regulation of phospholipase A2 and cyclooxygenase 2 in gastrointestinal tissues with special reference to colorectal cancer
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The phospholipases A2 (PLA2s) are phospholipid hydrolyzing enzymes that in mammalian cells exist in several different isoform including cytosolic PLA2 (cPLA2), group I PLA2 (PLA2-I) and group II PLA2 (PLA2-ll). PLA2 is involved in production of inflammatory mediators, membrane remodelling, digestive functions and stimulation of prolifemtion. In addition. PLA2 supplies cyclooxygenase COX-1 and COX-2 with arachidonic acid for production of eicosanoids.Increased COX-2 expression and high concentrations of prostaglandins have been found in human colorectal adenocarcinomas and in rat colonic twnours. Studies implicate that there is a link between the tumourigenic effect of the tumour suppressor gene adenomatous polyposis coli (APC) and COX-2 up-regulation in mouse intestinal neoplasms. Mutations of the human APC gene are frequent in both sporadic and familial colorectal cancer and result in activation of p-catenin!T cell factor-4 (Tcf-4) mediated transcription of target genes which may contribute to colorectal tumourigenesis.The ontogenic development of rat gastrointestinal PLA2-I and PLA2-II and the influence of the exogenous glucocorticoid cortisone acetate were studied. The ontogeny of rat glandular stomach PLA2-I and PLA2-II gene expression is similar and seems to follow the general postnatal development of the gastrointestinal tract PLA2-II gene expression is different in the glandular stomach compared to ileum and forestomach during the neonatal period. Administration of the cortisone acetate, during the neonatal period, induced PLA2-I and PLA2-II gene expression in glandular stomach and ileum, respectively, au effect that may be related to maturation of the gastrointestinal tract.Gene expression of PLA2-II, cPLA2 and COX-2, protein levels of COX-2 and mutational analysis of APC were investigated in human colorectal tumours. COX-2 was dramatically up-regulated in tumours located in rectum and associated with the presence of APC mutations. Tcf-4 consensus sequences found in the COX-2 promoter were activated but APC/P-catenin/fcf-4 pathway may partly be involved in transcriptional regulation of the COX-2 gene. Neither induction of PLA2-II nor correlation in gene expression between cPLA2 and COX-2 were observed. 'These observations imply that other enzymes than PLA2 contribute to generate arachidonic acid for COX-2 mediated eicosanoid metabolism aud that PLA2-II seems to play a minor or no role in hllltlan colorectal cancer.
|
|
| 8. |
- Dizdar (Dizdar Segrell), Nil
(författare)
-
Microdialysis as a Tool in Studies of L-Dopa and Metabolites in Malignant Melanoma and Parkinson’s Disease
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A model with human melanoma xenografts transplanted to athymic mice has been adopted for in vivo studies of 5-S-cysteinyldopa (an intermediate pigment metabolite), glutathione, and cysteine. L-Dopa is an intermediate metabolite in pigment formation and is also important in the treatment of Parkinson's disease, and therefore 1 have also studied the pharmacokinetics of this compound.We were first to describe in vivo microdialysis in melanoma tissue and showed that dialysis membranes of cuprophane or polyamide are suitable for studies of interstitial 5-S-cysteinyldopa and selected thiols. Analytical procedures were also improved for quantitation of 5-S-cysteinyldopa, L-dopa, glutathione, cysteine, and N-acetylcysteine (NAC). In the melanoma xenografts the interstitial concentration of 5-S-cysteinyldopa reflected the high intracellular production of this intermediate metabolite. For in vivo manipulation of glutathione in the melanoma tissue we gave intraperitoneal injection of buthionine sulphoximine to the animals and thus reduced the glutathione concentrations substantially. We showed that restitution of glutathione in melanoma tissue occurs spontaneously and is not much improved by treatment with the cysteine deliverers NAC and L-2-oxothiazolidine-4-carboxylate (OTC). 5-S-Cysteinyldopa was not substantially affected by great variations in glutathione concentrations. Transport of NAC from intraperitoneal injection to melanoma tissue occurred rapidly and deacetylation to cysteine in vivo could be detected soon after NAC injection. In vivo formation of cysteine was slower from OTC than from NAC.Pharmacokinetic studies of L-dopa in human subjects indicated a slight to moderate protein binding. Plasma free L-dopa had similar elimination T½ as interstitial L-dopa, but in some cases the elimination of total L-dopa was slower. Difficulties in intestinal absorption of L-dopa were revealed by microdialysis in blood and subcutaneous tissue. Studies showed that this was due to delayed emptying of the stomach. L-Dopa intake increased 5-S-cysteinyldopa concentrations in blood within 30 min in patients with Parkinson's disease and a history of melanoma. No melanoma activation occurred during long-term treatment with L-dopa.Microdialysis is thus a safe and easily applied method for in vivo studies of both pigment metabolites from human melanoma tissue transplanted to nude mice and for pharmacokinetic studies of L-dopa.
|
|
| 9. |
- Duchén M., Karel, 1961-
(författare)
-
Human milk factors and atopy in early childhood
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The protective effect of breast milk against atopic manifestations in infancy, i. e. atopic eczema and food allergy, has been controversial for the last decades. Differences in the composition of human milk could explain these controversies.Aims: To investigate the composition of milk antibodies, such as lgE, total S-IgA and S-IgA antibodies against food and inhalant allergens (B-lactoglobulin, ovalbumin and cat allergen) in milk from atopic and non atopic mothers. To study human milk nucleotide, polyamine and polyunsaturated fatty acid (PUFA) composition. Furthermore, the composition of these factors in maternal milk were related to the development of allergic disease in the children during the first 18 months of life.Methods: One hundred and twenty (120) children were followed at 3, 6, 12 and 18 months of age. Blood samples were obtained at birth and at 3 months. Skin prick tests were petformed at 6, 12 and 18 months and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly dming the lactation period. Total IgE antibodies were measured by RIA and S-IgA antibodies by ELISA. Milk nucleotides and polyamines were measured by HPLC and PUFA by gas chromatography.Results: Total IgE and total S-IgA levels were similar in colostrum from atopic and non atopic mothers, Total S-IgA levels were, however, lower in mature milk from atopic than from non atopic mothers. Levels of S-IgA antibodies against foods and cat, were similar in the two groups during the lactation period, except for low levels of anti-OVA S-lgA in colostrum of atopic mothers. Nucleotide composition was similar in milk from atopic and non atopic mothers. Low levels of putrescine and spermine were, however, found in mature milk from atopic mothers.Low levels of LA, LNA, n-6 LCP and n-3 LCP and particularly higher LAILNA and AA!EPA ratios were found in milk from atopic mothers at one month of lactation. Correlations between individual LCP levels were observed in milk from non atopic mothers. These correlations were absent in milk from atopic individuals, indicating a disturbed PUFA metabolism. The differences were less obvious in serum phospholipids from newboms.Total lgE, total S-IgA and S-IgA antibodies against foods and cat, as well as nucleotide and polyamine levels were similar in milk from mothers of allergic children. Lower levels of EPA in transitional milk and lower levels of EPA, DPA and DHA (p<0.05 for all) in mature milk were found in mothers of allergic as compared to mothers of non allergic children. Total n-6/total n-3 and AA/EPA ratios were low in both transitional and mature milk from mothers of allergic children. The disturbed correlations within the n-6 fatty acids in milk from atopic mothers were not related to the development of atopy in the children. In contrast, C20:4 n-3 correlated well to most of the n-6 fatty acid levels only in milk from non atopic mothers of non atopic children.The PUP A levels in serum from allergic and non allergic children were similar, except higher levels of C22:4 n-6 and C22:5 n-6 (p<0.05 for both) and higher AA!EPA ratio in serum phospho1ipids from the former group (p<0.05). Changes in levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n-6 PUPA. The AA!EPA ratio in maternal milk was related, however, to the AA/EPA only in serum from non allergic children, while this was not the case in allergic children.Conclusion: Low levels of anti-QV A S-IgA antibodies in colostrum and low levels of total S-IgA, putrescine and spermine in mature milk. were related to maternal atopy. Human milk IgE antibody and nucleotide composition were not related to maternal atopy. Neither of these milk factors were, however, related to development of anergic disease in children. Low levels of n-6 and n-3 PUFA in transitional milk were related to maternal atopy, particularly low levels of n-3 PUP A and high AA/EPA ratio in maternal milk and serum phospholipids in the infants were related to the development of allergy in the children. The milk PUPA composition influenced the composition of PUPA in serum phospholipids of the children. The findings are suggested to be partly related to a 8-6 desaturase dysfunction in atopic individuals.
|
|
| 10. |
- Edell-Gustafsson, Ulla, 1947-
(författare)
-
Sleep, psychological symptoms and quality of life in patients undergoing coronary artery bypass grafting
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis sleep, psychological symptoms and quality of life (Qol) in patients undergoing coronary artery bypass grafting (CABG) at the University Hospital in Linköping were evaluated. Interviews and 24-hour polysomnography were performed prior to surgery, immediately after surgery and again at one month, with a six-month-follow-up mailed questionnaire. Habitual sleep was evaluated using the Uppsala Sleep Inventory questionnaire and a diary the recorded mornings. The Spielberger State of Anxiety Scale and the Zung's Self-rating Depression Scale were used to measure anxiety and depression, respectively. Physical functional capacity was assessed according to the New York Heart Association's (NYHA) classes and Qol, with the Nottingham Health Profile instrument (NHP).A retrospective evaluation of nurse's documentation about sleep was also performed. In addition, the quality and quantity of sleep were assessed before surgery and in the immediate postoperative period in a pilot study, with a one-month follow-up interview. The results indicated disturbed sleep, and changes in behaviour and mental state after surgery due to fragmented sleep, pain and anxiety.Forty-four patients were examined prior to surgery. The results showed that almost two-fifths experienced too little sleep habitually and 50 % had a combination of at least two sleep problems. Poorer health, higher level of anxiety and increased difficulties maintaining sleep (DMS) were consistent with significantly longer sleep latency, increased fragmented sleep, and reduced stages 3 and 4 and RIM sleep measured by polysomnography. The level of Qol on the NBP was significantly associated with objectively measured sleep.In the immediate period following CABG there is a changed distribution of sleep, with a reduction of nocturnal sleep duration and an increase in daytime sleep, which had almost returned to preoperative values one month after surgery. Qol was significantly improved six months after surgery compared to before surgery.It was noted that patients with a more anxiety prone reactivity during six months following CABG had significantly more sleep disturbances, reduced energy and functional physical capacity, and lower quality of life, compared to those without such reactivity. Significantly more sleep disturbances, reduced energy and lower quality of life were more prominent among those with sadness/depression or cognitive/behavioural fatigue as reactions to sleep loss. A higher degree of cognitive/behavioural fatigue and dysphoria reactions were associated with a higher NYHA class.In conclusion, patients with coronary artery disease have poor quantity and quality of sleep. Increased psychological symptoms in patients with CAD prior to surgery were associated with greater symptoms six months after surgery. Physical functional capacity and quality of life were significantly improved six months after surgery.
|
|
