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| 2. |
- Aanestad, Øystein
(författare)
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Quantitative electromyographic studies of the perineal muscles in normal subjects and patients suffering from anal or urinary incontinence
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of the study were to characterize the interference pattern in perineal muscles in healthy subjects with the use of quantitative EMG techniques, to evaluate if prostatic surgery had any effect on the interference pattern and furthermore to examine the interference pattern in the perineal muscles in patients suffering from urinary or anal incontinence.The interference pattern in the perineal muscles was examined with a computerized analysis, the Turns and Amplitude (T/A) analysis, and the innervation pattern of the muscles was examined with single fiber electromyography measuring the fiber density. Reference values were collected from 30 normal subjects. The patient material consisted of 20 males subjected to transurethral prostatectomy (TUR-P), 10 males who underwent radical retropubic prostatectomy (RRP), 20 patients suffering from anal incontinence and 24 women withurinary incontinence.T/A analysis of the interference pattern in the perineal muscles in normal subjects showed a significant increase in number of turns/sec and mean amplitude correlating to increasing force but no age-related changes.TUR-P and RRP did effect the innervation of the distal urethral sphincter muscle as shown by increased fiber density indicating a peripheral nerve lesion. T/A analysis did not shown any increased activation of the distal urethral sphincter as a compensation for the loss in bladder neck sphincter function but rather signs of decreasedcentral activation.Patients with idiopathic faecal incontinence showed signs of impaired innervation of the external anal sphincter muscle. A decreased interference pattern at maximal contraction indicated a reduced central activation of perineal muscles, in particular for patients with partial rupture of the external anal sphincter muscle. The reduced central activation could play a role for the aetiology of faecal incontinence.Patients with urinary stress incontinence also showed signs of impaired innervation of the external anal sphincter muscle as well as reduced interference pattern at maximal contraction and during continuous recording of the EMG activity during cystometry. A reduced central activation of the motor units was predicted as one factor involved in the aetiology.
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| 3. |
- Aarts, Clara
(författare)
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Exclusive breastfeeding-Does it make a difference? : A longitudinal, prospective study of daily feeding practices, health and growth in a sample of Swedish infants
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The concept of exclusive breastfeeding in relation to daily feeding practices and to health and growth of infants in an affluent society was examined. In a descriptive longitudinal prospective study 506 mother-infant pairs were followed from birth through the greater part of the first year. Feeding was recorded daily, and health and growth were recorded fortnightly. Large individual variations were seen in breastfeeding patterns. A wide discrepancy between the exclusive breastfeeding rates obtained from "current status" data and data "since birth" was found.Using a strict definition of exclusive breastfeeding from birth and taking into account the reasons for giving complementary feeding, the study showed that many exclusively breastfed infants had infections early in life, the incidence of which increased with age, despite continuation of exclusive breastfeeding. However, truly exclusively breastfed infants seem less likely to suffer infections than infants who receive formula in addition to breast milk. Increasing formula use was associated with an increasing likelihood of suffering respiratory illnesses. The growth of exclusively breastfed infants was similar to that of infants who were not exclusively breastfed. The health of newborn infants during the first year of life was associated with factors other than feeding practices alone. Some of these factors may be prenatal, since increasing birth weight was associated with an increasing likelihood of having respiratory symptoms, even in exclusively breastfed infants. However, exclusive breastfeeding was shown to be beneficial for the health of the infant even in an affluent society.
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| 4. |
- Acosta, Stefan, 1967-
(författare)
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On Acute Thrombo-Embolic Occlusion of the Superior Mesenteric Artery
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods. Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease.Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor.A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions.Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.
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- Adalberth, Gunnar
(författare)
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Total knee arthroplasty : Alternative aspects on fixation, design and postoperative treatment
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Total knee arthroplasty as a treatment of severe gonarthrosis has become a great success, but tibial component loosening is still a major reason for failure. When total knee arthroplasty was introduced, only all-polyethylene (AP) tibial components were available. Based on mostly theoretical data, AP components were more or less abandoned during the 1980:ies in favor of metal-backed (MB) tibial components. The aim of the present study was to evaluate whether insufficient fixation would result, using an all-polyethylene tibial component instead of a more costly metal-backed prosthesis. Further, to compare different antibiotic loaded bone cements, and to investigate whether post- operative drainage is beneficial in total knee arthroplasty. Radiostereometric analysis (RSA) was used to obtain accurate and standardized evaluations facilitating comparison between prosthetic designs.Magnitude and pattern of migration of a moderately conforming AP tibial component was analyzed in 22 patients. Migration was on par with a more conforming previously used frequently, AP component, indicating a favorable prognosis regarding future aseptic loosening. Another 34 arthroplasties with a flat on flat (non-conforming) articulating geometry were randomized to an AP or MB cemented tibial component. There were no differences in migration between the groups. None of the AP implants displayed any continuous migration between 1 and 2 years postoperative. In a similar randomized series of 38 arthroplasties with a semiconstrained articulation, fixation measured with RSA was not inferior for AP implants compared with MB. Both studies indicate a good long-term prognosis using an AP component. A new antibiotic loaded bone cement was prospectively randomized against a more commonly used bone cement in a series of 51 arthroplasties. Neither fixation of the tibial component nor the radiographic and clinical results differed between the cements, indicating a good prognosis for the new cement. Postoperative drainage of knee arthroplasty is widely used. 90 patients were prospectively randomized into three groups: no drain, ordinary drain system and a retransfusable drain system. Postoperative drainage in knee arthroplasty has no adverse clinical consequences but seems not to be necessary.
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- Afrakhte, Mozhgan
(författare)
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Growth control mechanisms in normal and neoplastic mammalian cells
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main theme of the studies presented in this thesis is, the growth control mechanisms whose loss in normal cells predispose to or cause cancer. The balance between growth inhibitory and stimulatory mechanisms is crucial for the development and maintenance of a normal animal.PDGF, a growth factor for cells of mesenchymal origin, is implicated in normal developmental processes as well as neoplasia. The alternative splicing of exon 6 in PDGF-A gene transcripts gives rise to two different proteins with different compartmentalization properties. The PDGF-A chain homodimers, PDGF-AAL, encoded PDGF A-splice variant remain associated with the cell membrane. Studies of a human fibrosarcoma cell line, U-2197, revealed a high expression level of the cell associated PDGF-AAL which upon release increased autophosphorylation of the endogenous PDGF receptors, suggesting an autocrine loop. PDGF-A gene and PDGFR-α gene found to be co-amplified in the U-2197, indicating an optimised system for growth in these cells, i.e. amplified growth factor receptor as well as a local autocrine supply of the mitogen.Members of TGFβ superfamily are potent regulators of the growth and differentiation of a wide range of cell types. Intracellular mediators of TGF-β signalling, SMADs, transduce signals from serine/threonine kinase receptors to the nucleus where they affect transcription of target genes. A new class of SMAD proteins has been identified whose members, the inhibitory SMADS, antagonise TGF-β signals by interfering with agonistic SMADs activity. Smad6 and Smad7 are two closely related TGF-β antagonists identified in mammalian cells. Overexpression of Smad7 inhibited the cellular response to TGF-β whereas expression of an anti-sense Smad7 construct showed an enhancing effect on this response. The inhibitory SMADs may act in a negative feedback loop, as their expression is induced by the same ligands whose action they antagonise.Density dependent growth inhibition is a growth control mechanism often lost in transformed and malignant cells. Cells in dense culture are refractory to the mitogen stimulation although, the mitogenic signals were shown to be processed to some extent. The expression of immediate-early genes in dense culture stimulated with mitogen was induced. The activity of cyclin dependent kinases (CDKs), the pivotal kinases in G1/S transition, showed to be density dependent and decreased by increasing cell density. pRb, a tumour suppressor and growth regulatory protein, remained unphosphorylated in mitogen treated dense culture. The cessation of CDKs kinase activity in dense cultures was shown to be accompanied with increasing expression of inhibitory proteins of these kinases, CKIs. The impaired expression of a positive regulator of CDKs, Cdc25A phosphatase, was another feature of dense cultures.
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| 8. |
- Ahlgren, Johan, 1960-
(författare)
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Studies on Prediction of Axillary Lymph Node Status in Invasive Breast Cancer
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most common malignancy among females in Sweden. Axillary lymph-node dissection is a standard procedure in the management of breast cancer, aiming at obtaining prognostic information for adjuvant therapy decisions. Axillary dissection entails considerable morbidity. The aims of this study were to establish more selective surgical approaches and to investigate angiogenesis, a potential predictor for lymph-node metastases and prognosis.Clinical nodal status, tumour size and S-phase were associated with nodal metastases in cohort of 1145 women. The proportion of nodal metastases was 13% in the subgroup with the lowest risk.In a study from two registries, 675 and 1035 breast cancers ≤10 mm diagnosed by screening mammography had nodal metastases in 6,5% and 7%, respectively. Clinically detected cancers had a risk of 16% and 14%, respectively.In a study on 415 women, a 5-node biopsy of the axilla had a sensitivity of 97,3% and a false negative rate of 2,7% in comparison with axillary dissection.Six sections from 21 breast cancers were analysed for microvessel density (MVD). The inter-section variation contributed more to the total variance than inter-tumour variation, 45,0% and 37,3%, respectively.In a cohort of 315 women, breast cancers with high MVD more frequently had p53 mutations (27,1%) compared with cases with low MVD (18,4%). This difference was not statistically significant (p=0,075). p53 mutations were associated with a worse outcome, whereas MVD was not.In conclusion, women with screening detected ≤10 mm breast cancers have a low risk of lymph node metastases and some may not need axillary dissection in the future. The 5-node biopsy could be an alternative to axillary dissection. MVD is associated with methodological weaknesses and routine use is not recommended.
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| 9. |
- Ahmad, Abdulbaghi, 1951-
(författare)
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Childhood trauma and posttraumatic stress disorder : A developmental and cross-cultural approach
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis aims to identify child-specific cross-cultural protecting and vulnerability factors regarding traumatic experiences and posttraumatic stress reactions. Children between 6-18 years were interviewed from three different socio-cultural backgrounds. In Iraqi Kurdistan, 20 participants in a mass-escape tragedy (MET), 54 orphans and 45 survivors of the genocide operation "Anfal" were interviewed. In Sweden, a sample of 32 Kurdistanian refugee children and a comparable Swedish sample were included. The frequencies of posttraumatic stress disorder (PTSD) were 20%, 43%. 87%, 9,7% and 12.5% respectively.The relatively low frequencies of PTSD in the follow-up sample 2 months, 4 months, 14 months and 26 months after the MET suggest the child functioning in a complete, authoritative family, as a protecting factor. The significant of this developmentally based child-specific functioning level within the supportive family system can also explain the fluctuating PTSD-related symptom scores in this sample parallel to the changes in the socio-economic situation in the region. The over time decrease in behavioural problems among fostercare orphans and their low PTSD frequencies as compared with the increase in behavioural problems and the high PTSD frequencies among orphanage samples further support this suggestion. Child trauma scores and captivity duration predicted for PTSD in "Anfal" survivors, irrespective of parents' trauma scores and PTSD or fathers re-union with the family, suggesting child-specific vulnerability more than contagion effect. Despite PTSD, children in Kurdistan performed high functioning levels, probably indicating a child-specific manifestation of hypervigilance. The Kurdistanian refugee sample revealed lower lifetime reexperiencing PTSD symptom scores than the Swedish sample, indicating a healing effect on the former coming to Sweden and a resilience deficit for the later growing up in a highly sheltered society.There are more similarities than differences between children from Kurdistan and Sweden in reporting traumatic experiences and exhibiting posttraumatic stress symptoms. Developmentally based child characteristics have a determinant role as protective or vulnerability factors in childhood trauma and PTSD, even if socio-cultural factors also play a role.
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| 10. |
- Ahmed, Meftun
(författare)
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Oscillatory Ca2+ signaling in glucose-stimulated murine pancreatic β-cells : Modulation by amino acids, glucagon, caffeine and ryanodine
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Oscillations in cytoplasmic Ca2+ concentration ([Ca2+]i) is the key signal in glucose-stimulated β-cells governing pulsatile insulin release. The glucose response of mouse β-cells is often manifested as slow oscillations and rapid transients of [Ca2+] i. In the present study, microfluorometric technique was used to evaluate the role of amino acids, glucagon, ryanodine and caffeine on the generation and maintenance of [Ca2+] i oscillations and transients in individual murine β-cells and isolated mouse pancreatic islets. The amino acids glycine, alanine and arginine, at around their physiological concentrations, transformed the glucose-induced slow oscillations of [Ca2+] i in isolated mouse β-cells into sustained elevation. Increased Ca2+ entry promoted the reappearance of the slow [Ca2+] i oscillations. The [Ca2+] i oscillations were more resistant to amino acid transformation in intact islets, supporting the idea that cellular interactions are important for maintaining the oscillatory activity. Individual rat β-cells responded to glucose stimulation with slow [Ca2+] i oscillations due to periodic entry of Ca2+ as well as with transients evoked by mobilization of intracellular stores. The [Ca2+] i oscillations in rat β-cells had a slightly lower frequency than those in mouse β-cells and were more easily transformed into sustained elevation in the presence of glucagon or caffeine. The transients of [Ca2+] i were more common in rat than in mouse β-cells and often appeared in synchrony also in cells lacking physical contact. Depolarization enhanced the generation of [Ca2+] i transients. In accordance with the idea that β-cells have functionally active ryanodine receptors, it was found that ryanodine sometimes restored oscillatory activity abolished by caffeine. However, the IP3 receptors are the major Ca2+ release channels both in β-cells from rats and mice. Single β-cells from ob/ob mice did not differ from those of lean controls with regard to frequency, amplitudes and half-widths of the slow [Ca2+] i oscillations. Nevertheless, there was an excessive firing of [Ca2+] i transients in the β-cells from the ob/ob mice, which was suppressed by leptin at close to physiological concentrations. The enhanced firing of [Ca2+] i transients in ob/ob mouse β-cells may be due to the absence of leptin and mediated by activation of the phospholipase C signaling pathway.
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