A short- and long-term follow-up study of intersphincteric NASHA Dx implants for fecal incontinence.

BACKGROUND: The bulking agent NASHA Dx injected into the submucosal layer is effective in the treatment of fecal incontinence (FI) at short-and medium-term follow-up but efficacy after injection in the intersphincteric location is unknown. The aim of this study was to determine the short- and long-term efficacy and safety of NASHA Dx injected into the intersphincteric location for FI. METHODS: Patients were recruited from referrals to our Department for treatment of FI in November 2008-January 2010. Eligible patients were injected with 8 ml of NASHA Dx. Patients with a subtotal treatment effect were retreated after 2-4 weeks. The change in number of fecal incontinence episodes, the proportion of responders defined as at least 50% decrease in number of FI episodes and side effects were the main outcome measures. RESULTS: Sixteen patients, 15 women and 1 man with a median age of 68, 5 (range 44-80) years and a median CCFIS of 15 (range 10-19) were included in the study. The median number of incontinence episodes decreased from 21.5 (range 8-61) at baseline to 10 (range 0-30) at 6 months (p = 0.003) and 6 (range 0-44) at 12 months (p = 0.05). The median number of incontinence episodes in the 11 patients completing the 10-year follow-up was 26.5 (range 0-68). The percentage of responders at 12 months and 10 years were 56% and 27%, respectively. Mild to moderate pain at the injection site was described by 69%. There was one case of mild infection, successfully treated with antibiotics and one implant had to be removed due to dislocation. CONCLUSIONS: NASHA Dx as an intersphincteric implant improves incontinence symptoms in the short term with moderate side effects and can be used alone or as an adjunct to other treatment modalities. Long-term efficacy was observed in 27%.

A left-handed 3(1) helical conformation in the Alzheimer Abeta(12-28) peptide.

We show for the first time that the secondary structure of the Alzheimer beta-peptide is in a temperature-dependent equilibrium between an extended left-handed 3(1) helix and a flexible random coil conformation. Circular dichroism spectra, recorded at 0.03 mM peptide concentration, show that the equilibrium is shifted towards increasing left-handed 3(1) helix structure towards lower temperatures. High resolution nuclear magnetic resonance (NMR) spectroscopy has been used to study the Alzheimer peptide fragment Abeta(12-28) in aqueous solution at 0 degrees C and higher temperatures. NMR translation diffusion measurements show that the observed peptide is in monomeric form. The chemical shift dispersion of the amide protons increases towards lower temperatures, in agreement with the increased population of a well-ordered secondary structure. The solvent exchange rates of the amide protons at 0 degrees C and pH 4.5 vary within at least two orders of magnitude. The lowest exchange rates (0.03-0.04 min(-1)) imply that the corresponding amide protons may be involved in hydrogen bonding with neighboring side chains.

A TD-DFT study of the photochemistry of urocanic acid in biologically relevant ionic, rotameric, and protomeric forms.

The photochemistry of Urocanic acid, a chromophore present in human skin and linked to photoimmunosuppression and skin cancer, is investigated theoretically by means of time-dependent density functional theory. Extensive calculations are carried out for different ionic, rotameric, and protomeric forms of both the trans and cis form. Inclusion of solvation effects, here accounted for by means of a continuum solvent model, are found to be crucial for the correct description of the biologically relevant zwitterionic forms of the molecule. For the trans zwitterionic form, it is found that the planar form usually assumed in the literature is not stable, and that a realistic charge separation cannot be achieved in the gas phase. Calculated vertical excitation energies are in excellent agreement with available experimental data, with a weakly absorbing n --> pi transition around 4.0 eV, and strongly absorbing pi --> pi transitions at 4.5-4.9 eV. The debated intramolecular hydrogen bond is predicted to have a modest impact on the vertical spectra in solution, but improves agreement with experiment when included. In general, we also predict that different rotameric forms have very similar absorption spectra. In addition, we find a candidate absorbing state to link trans-urocanic acid to singlet oxygen production and subsequent photoaging of the skin.

Interaction of MyoD family proteins with enhancers of acetylcholine receptor subunit genes in vivo.

The myogenic determination factors (MDFs) are transcriptional activators that target E boxes in many muscle-specific promoters, including those of the genes coding for the subunits of the acetylcholine receptor. It is not known, however, if in vivo a given E box in a transcriptionally active gene is occupied, either uniquely by one MDF or randomly by all MDFs. We have analyzed expression of MDF and acetylcholine receptor subunits in cultured mouse muscle cells and, using chromatin immunoprecipitation, have determined which individual MDFs reside at promoters of several receptor subunit genes. We find that before fusion, C2C12 cells express myf-5, MyoD, and myogenin, all of which take up residence at promoters of all subunits except epsilon. At this stage, herculin is present in limited amounts and is detected mainly at the gamma and delta subunit genes. On myotube formation, herculin reaches high levels; concomitantly, the epsilon subunit gene becomes a common MDF target and begins to be expressed. In general, any MDF protein that is expressed also is present on transcriptionally active receptor genes; transcriptional activity of target genes correlates with occupancy by MDF, in particular, herculin.

The natural course of allergic rhinitis during 12 years of follow-up.

As symptoms of allergic rhinitis are generally thought to disappear with increasing age, we decided to follow up our allergic rhinitis patients to ascertain whether their disease had regressed or progressed, and whether they had developed respiratory symptoms. At our department, between 1979 and 1982, allergic rhinitis was diagnosed in 108 patients. In 1993, 82 of the patients (40 women, 42 men; mean age 36 years), none of whom had received immunotherapy, answered a questionnaire concerning the status of their allergic rhinitis, and any development of the disease during the interim. Of the 82 patients, one was free of allergic symptoms and 39% had become better; symptoms were unchanged in 39% of cases, and worse in 21%. Six percent had suffered from asthma at presentation, 6% had developed asthma in the interim, and 34% reported other lower airways symptoms. Neither sex nor age at diagnosis was a determinant of the course of allergic rhinitis. Thus, in contrast to findings in other studies, the severity of allergic rhinitis seems to have increased among our patients.

Organization of a breast tumour clinic and aspects of data analysis of a clinical material.

With the aim of making it easier for patients with tumours or suspected tumours of the breast to obtain adequate medical advice and treatment, a special breast tumour clinic was established at the Department of Surgery of the University Hospital in Uppsala for women resident in the county of Uppsala. The waiting time was less than one week. In addition to palpation, fine-needle biopsy with cytological examination, mammography and xeroradiography were performed. Close co-operation between a few doctors responsible for the various diagnostic units made it possible to give the patients quick service and contributed to an efficient use of the diagnostic resources. The clinic functioned mainly within the framework of the existing medical care facilities and did not act as a screening project. Over a period of 15 months, 1244 women were examined. 116 had breast cancer, and 5 of these tumours were occult. A comparatively low mean tumour size and a low frequency of lymph node metastases would seem to indicate that the patients came under medical care at a relatively early stage. For recording of the case histories and examination findings, special medical records permitting data processing were used. This has facilitated follow-up of the patients, special checks on certain patient groups, statistical analyses and prospective investigations. We consider that, for the patient, a clinic of this kind offers considerable psychological and financial benefits, and that for the health service as a whole it means increased efficiency and a lower cost per patient. It seems probable that both the patient's and the doctor's delay are reduced.

A computer based system for gynecological cytology.

A computer system is described for cytological report and registration routines in gynecological practice. The sociomedical advantages of the integration of such a computer system with a previously described computer system for organized pynecological health control are pointed out.