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Liver transplantation is the only definitive treatment for transthyretin amyloidosis, with an excellent 5-year survival in endemic countries where the Met30 mutation is predominant. We report our experience of liver transplantation for transthyretin amyloidosis. We reviewed the clinical records of 17 transplanted patients (11 males, 6 females; age at liver transplant: 45.7±11.7 years). We had a wide spectrum of non-Met30 mutations (52.9%), with a predominance of Gln89 (23.5%). Five-year survival after transplantation was 43.8%; at multivariate analysis, both non-Met30 mutations (HR 17.3, 95% CI 1.03-291.7) and modified BMI (HR 0.50, 95% CI 0.29-0.87) showed significant and independent prognostic roles (P=0.048 and P=0.015, respectively). Five out of the 9 non-Met30 carriers received combined heart transplantation because of severe cardiomyopathy; they showed a trend towards a better prognosis vs. the 4 patients who did not receive combined heart transplantation (although not statistically significant; P=0.095). At follow-up, no significant improvement of transthyretin amyloidosis manifestations was observed. The results of liver transplantation for transthyretin amyloidosis in our population are poorer than those reported in the literature probably because of the high prevalence of non-Met30 mutations.

I Sverige drabbas mellan 100-150 personer varje år av en ryggmärgsskada i samband med ett trauma. För de drabbade innebär det en förlorad kroppsfunktion av varierande grad samt en ny livssituation att förhålla sig till. Syftet är att beskriva hur livsvärlden påverkas hos män i arbetsför ålder 18-65 år som drabbas av en traumatisk ryggmärgsskada. För att beskriva detta gjordes en litteraturstudie på kvalitativa och kvantitativa artiklar som granskades. Resultatet visade på två huvudteman, lidandets dimensioner och lindrat lidande. I lidandets dimensioner beskrevs aktuella problem som uppstod i samband med skadan. Vid lindrat lidande beskrevs olika sätt att hantera och bearbeta den traumatiska händelsen samt vad den nya livssituationen med en ryggmärgsskada innebar för individen. Resultatet visade på vikten av att vården utformas utifrån målet att individen blir så självständig som möjligt. Genom självständighet hos individen blev upplevelsen av beroende och skammen över att vara en börda på andra minskad. Resultatet visade även att patienter kände otrygghet då de upplevde okunskap hos personalen. I diskussionen läggs vikten på sjuksköterskans kunskap om ryggmärgsskador samt att sjuksköterskan kontinuerligt ger information och stöd till individen och de anhöriga. Ett gott stöd från sjuksköterskan visade sig vara en viktig faktor i krishanteringen. Det framkom att de anhöriga behöver stöd i form av samtal och delaktighet. Till sist diskuteras det hur detta kan impliceras i vården.

Introduzione L’efficacia dei chemio/radioterapici ha aumentato notevolmente l’aspettativa di vita delle pazienti oncologiche, tuttavia, questi trattamenti possono compromettere la funzionalità ovarica. La crioconservazione di tessuto ovarico, con il successivo reimpianto, ha lo scopo di preservare la fertilità delle pazienti a rischio di fallimento ovarico precoce. Scopo dello studio Definire la migliore procedura di crioconservazione e reimpianto in grado di ottenere la neovascolarizzazione del tessuto reimpiantato nel minor tempo possibile al fine di diminuire la perdita follicolare causata dall’ischemia durante la procedura. Materiali e metodi Per ciascuna paziente (3) le biopsie ovariche, sono state prelevate laparoscopicamente e crioconservate secondo il protocollo di congelamento lento/scongelamento rapido. Campioni di corticale ovarica sono stati processati per l’analisi istologica, ultrastrutturale, immuistochimica e confocale per valutare la preservazione morfologiaca del tessuto. Le fettine di corticale ovarica sono state scongelate e reimpiantate ortotopicamente (2), nelle ovaia e in due tasche peritoneali, o eterotopicamente (1), in due tasche create nel sottocute sovrapubico. Risultati Le analisi di microscopia hanno mostrato il mantenimento di una discreta morfologia dello stroma, e dei vasi criopreservati e un lieve ma non significativo danneggiamento dei follicoli scongelati. Tutte le pazienti hanno mostrato la ripresa della funzionalità endocrina rispettivamente dopo 2/4 mesi dal reimpianto. Il color-doppler, inoltre ha rivelato un significativo aumento della vascolarizzazione ovarica rispetto alla quasi totale assenza di vascolarizzazione prima del reimpianto, quando le pazienti mostravano una conclamata menopausa. Conclusioni Lo studio ha confermato la ripresa della vascolarizzazione dell’ovaio in seguito a reimpianto avascolare di fettine di corticale, senza l’impiego di fattori esogeni o meccanici aggiuntivi, in tempi concordanti con i dati della letteratura. I risultati sono incoraggianti e l’avanzare degli studi e della ricerca potranno contribuire allo sviluppo di nuove metodologie di reimpianto che possano avere un successo clinico ed una sicurezza superiori a quelle finora ottenute. / Recent advances in the diagnosis and the introduction of new protocols of chemo/radiotherapy have significantly increased the survival rate of oncological patients. However, these treatments are gonadotoxic and can severely affect the reproductive potential of patients. Ovarian tissue cryopreservation represents a valid strategy to preserve reproductive function and steroidogenic activity in patients with a high risk of POF. The aim of this procedure is to reimplant cryopreserved ovarian cortical strips allowing the recovering of vascularization and ovarian function. Biopsies samples were laparoscopically removed from both ovaries (3 oncological patients) and frozen according to the slow freezing rapid thawing protocol. Samples of ovarian cortex were processed for histological, ultrastructural, confocal and immuistochimica analysis, to evaluate the morfologiacal tissue preservation. The slices of ovarian cortex were thawed and replanted orthotopically (2), in the ovary and in two peritoneal pockets, or eterotopically (1), in two pockets created in the suprapubic subcutaneous tissue. The microscopy analysis have shown maintenance of a discrete morphology of the cryopreserved stroma, and vessels and a slight but not significant damage to the thawed follicles. All patients showed the resumption of endocrine function respectively after 2/4 months after planting. The color-doppler, also revealed a significant increase in ovarian blood flow compared to the almost total absence of vascularization before replanting, when the patients showed n menopause. The study has confirmed the recovery of the vascularization of the ovary after avascular replanting of cortical slices slices, without the use of exogenous factors , in times consistent with the literature data. The results are encouraging and advancing studies and research will contribute to the development of new methods of reimplant that may have better clinical success and security than those obtained.

Purpose: Current literature reports that between 7 and 14% of young, healthy women have stress urinary incontinence (SUI). No gold standard exists for quantifying urine leakage, although pad tests have been used in older, parous populations. The aim of this study was to determine the reliability and accuracy of a new pad test for young, healthy women with SUI. Methods: The pad test consisted of measuring quantity of leakage after the following activities: stair running, standing up from sitting, curl-ups, running on the spot, jumping jacks, jumping on a mini-trampoline and coughing vigorously. Bladder volume was standardised by having the volunteers drink one litre of water one hour prior to the testing. The volunteers performed the pad test on two consecutive days. Results: Sixteen nulliparous women between the ages of 18 and 30 years (7 controls and 9 with SUI) participated in this study. The mean increase in pad weight was 0.64 g (± 0.50) in the continent group and 11.89 g (± 20.32) in the group with SUI. There was no significant difference in pad weight between the testing sessions (p=0.228), however the test was not able to elicit measureable urine loss in 3 participants with SUI. Pad weights between the two groups of women were significantly different (p=0.023). The test re-test ICC for the continent group was 0.845 (95% CI: 0.139–0.973) and 0.782 (95% CI: -0.040–0.952) for the group with SUI. Significance: The results of this study support the use of this pad test in healthy young women with SUI; it appears to be reliable and challenging enough to cause measureable urine loss in the majority, and it may be useful for diagnosing and quantifying SUI without urodynamic studies.

Human Papillomavirus (HPV) is one of the most common causes of sexually transmitted disease worldwide. Infections by high-risk HPVs, such as HPV-18, have been associated etiologically with cervical cancer. The successful development of HPV vaccines may be beneficial to the HPV-na??ve population, but women that have already been exposed to the virus are still at risk of developing HPV-associated malignancies. A need for a systemic cure for HPV-infection therefore still exists. Gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers; however, few studies have explored this possibility for cervical cancer. The aim of this project is to construct a gene expression vector that can specifically target HPV-infected cervical cancer cells, by making use of the activity and selectivity of the P105 promoter which is determined by transcription control elements within the HPV-18 long control region (LCR). The first part of this study involved the construction of LCR deletion plasmids, and examining the subsequent level of gene expression induced within different mammalian cell lines. The results suggest the LCR to be capable in achieving cervical cancer-specific gene expression. The 3′-end of the viral L1 gene upstream of the LCR appeared to have a repressive effect on the promoter and therefore should be excluded for maximum LCR promoter activity. The second part of the project involved site-directed mutagenesis studies performed on selected transcription factor binding sites with an attempt to further increase the level of LCR promoter activity and specificity towards HPV-infected cervical cancer cells. The results suggest that a GRE/YY1 mutation may significantly enhance promoter activity. In terms of promoter regulation, the E2BSs appeared to be responsible for promoter activation in the absence of viral E2 proteins. The findings of this study suggest a possible gene therapy approach towards the treatment of cervical cancer. By making use of the activity and specificity of the HPV-18 P105 promoter to induce cervical carcinoma-specific expression of appropriate therapeutic genes, suicidal phenotypes can be introduced selectively within HPV-positive cervical cancer cells while normal HPV-negative cells are unaffected.

Proefschrift Universiteit van Amsterdam. / Auteursnaam op omslag: Fanny Lauw. Met lit. opg. - Met samenvatting in het Nederlands.

Zugl.: Dortmund, Univ., Diss., 2006

Techn. Universiẗat, Diss., 2006--München.