Neurofibromatosis type I with breast cancer: not only for women!

The association of neurofibromatosis type I with invasive male breast cancer is a rare clinical entity with only one case in literature reported in 1953. Women with NF1 are at risk of developing breast cancer and men also may be at risk but there is scarce data on the risk and association of NF1 with male breast cancer due to its rarity. Established clinical trials in male breast cancer patients are lacking and the results are extrapolated from female breast cancer patients. The treatment of male breast cancer is followed as per the guidelines of premenopausal female breast cancer and tamoxifen is the hormone treatment in them. Mendes et al suggests that silencing of NF1 gene confers resistance to tamoxifen. Our conclusions are that since NF1 is mutated or deleted in one third of sporadic breast cancers, its role as a molecular driver for treatment has to be further explored.     

Imbalance between Angiotensin II - Angiotensin (1-7) system is associated with vascular endothelial dysfunction and inflammation in type 2 diabetes with newly diagnosed hypertension

AimDiabetes is associated with Renin-angiotensin-aldosterone-system (RAAS) activation. Protective role of Angiotensin (1-7) has been recently identified. The study aims to identify associations between imbalance in RAAS components with vascular endothelial dysfunction and inflammation in diabetics with newly diagnosed hypertension.MethodsBrachial Flow-mediated-dilation (FMD), Carotid Intima-media-thickness (CIMT), pulse-wave-velocity (PWV), Serum E-selectin, Vascular-Cell-Adhesion-Molecule-1 (VCAM-1), high-sensitivity C-Reactive Protein (hsCRP), Interleukin-10 (IL-10), Renin, AngiotensinII, Angiotensin-Converting-Enzyme 2 (ACE2) and Angiotensin1-7 were measured in 60 diabetic patients with newly diagnosed hypertension. Patients with AngiotensinII/Angiotensin1-7 ratio <1 were classified as Favourable-Axis (FA) group (n = 22) and those with ratio >1 were classified as Unfavourable-Axis (UA) group (n = 38).ResultshsCRP was higher [9.52 (4.64–16.19) vs 3.62 (1.77–13.09) (mg/l), p = 0.04], IL-10 was lower [2.26 (1.34–12.05) vs 10.98 (4.44–17.78) (pg/ml),p = 0.006], %FMD was lower [(5.51 ± 2.97) vs (7.66 ± 3.38) (%), p = 0.01] and CIMT was higher in UA compared to FA group [0.7 (0.55–0.79) vs 0.51 (0.49–0.65) (mm), p = 0.001]. Renin correlated positively with pressure, PWV, E-selectin and VCAM-1, opposing associations were obtained for Angiotensin1-7 and ACE2.ConclusionImbalance between AngiotensinII – Angiotensin1-7 is associated with increased inflammation and vascular dysfunction in diabetics and can contribute to development of hypertension in these patients.     

Long-term stability of orthodontic treatment and patient satisfaction. A systematic review

OBJECTIVE: To evaluate morphologic stability and patient satisfaction at least 5 years after orthodontic treatment. MATERIALS AND METHODS: Published literature was searched through the PubMed and Cochrane Library electronic databases from 1966 to January 2005. The search was performed by an information specialist at the Swedish Council on Technology Assessment in Health Care. The inclusion criteria consisted of a follow-up period of at least 5 years postretention; randomized clinical trials, prospective or retrospective clinical controlled studies, and cohort studies; and orthodontic treatment including fixed or removable appliances, selective grinding, or extractions. Two reviewers extracted the data independently and also assessed the quality of the studies. RESULTS: The search strategy resulted in 1004 abstracts or full-text articles, of which 38 met the inclusion criteria. Treatment of crowding resulted in successful dental alignment. However, the mandibular arch length and width gradually decreased, and crowding of the lower anterior teeth reoccurred postretention. This condition was unpredictable at the individual level (limited evidence). Treatment of Angle Class II division 1 malocclusion with Herbst appliance normalized the occlusion. Relapse occurred but could not be predicted at the individual level (limited evidence). The scientific evidence was insufficient for conclusions on treatment of cross-bite, Angle Class III, open bite, and various other malocclusions as well as on patient satisfaction in a long-term perspective. CONCLUSIONS: This review has exposed the difficulties in drawing meaningful evidence-based conclusions often because of the inherent problems of retrospective and uncontrolled study design.     

Experimental Nasal Intubation: A Study of Changes in Nasoantral Mucosa and Bacterial Flora

Objectives: To investigate the local effects in a nasal cavity and its adjacent sinuses of long-term detention of an endonasal tube, with special attention to inflammatory pathology and microbiology. Study Design: Experimental rabbit study. Methods: Four groups of 4 rabbits, in all 16, were unilaterally nasally intubated and evaluated macroscopically, histopathologically, and bacteriologically after 1, 2, 4, and 8 weeks, respectively. Results: At first, in the 1- and 2-week groups to the 4-week group, histopathology, such as degeneration of olfactory mucosa, squamous cell metaplasia, and polyp formations, was observed together with frequent opportunistic bacterial findings in the nasal cavity. Later, in the 4- and 8-week groups, inflammatory mucosal changes, such as septal increase of connective tissue, goblet cell hyperplasia, and epithelial invaginations, were found in the nasal cavity containing a tube. A concomitant increase was found of commensal bacteria adjacent to the tube and the similar bacterial findings in the ipsilateral maxillary sinuses. However, there were no signs of inflammatory reactions in the sinuses. Conclusions: Our investigation points to the tube as the cause of local goblet cell hyperplasia with an increased mucus production, and as a food source for the commensals with a marked increase of the amount of bacteria. The positive bacterial cultures from the maxillary sinuses might be considered to be colonization. However, because of the possibility of contamination, improved sampling techniques are required, as are further studies.     

Immunocytochemical detection and mapping of a cytokeratin 18 neo-epitope exposed during early apoptosis

A neo-epitope in cytokeratin 18 (CK18) that becomes available at an early caspase cleavage event during apoptosis and is not detectable in vital epithelial cells is characterized. The monoclonal antibody M30, specific for this site, can be utilized specifically to recognize apoptotic cells, which show cytoplasmic cytokeratin filaments and aggregates after immunohistochemistry with M30, while viable and necrotic cells are negative. The number of cells recognized by the antibody increases after induction of apoptosis in exponentially growing epithelial cell lines and immunoreactivity is independent of the phosphorylation state of the cytokeratins. The generation of the M30 neo-epitope occurs early in the apoptotic cascade, before annexin V reactivity or positive DNA nick end labelling. In a flow cytometric assay, the majority of the M30-positive cells appear in the ‘apoptotic’ subG1 peak. Tests with synthetic peptides define positions 387–396 of CK18, with a liberated C-terminus at the caspase cleavage site DALD-S, as the ten-residue epitope of M30. This epitope starts at the end of coil 2 of the predicted CK18 structure, at a probable hinge region, compatible with the sensitivity to proteolytic cleavage. The definition of a specific caspase cleavage site in CK18 as a neo-epitope can be used for quantification of apoptotic epithelial cells with immunocytochemical techniques and is applicable to both fresh and formalin-fixed material. Copyright © 1999 John Wiley & Sons, Ltd.     

Short or long consultations? Primary care nurses’ considerations in making appointments with general practitioners

In Sweden primary care nurses (PCNs) at the health centres (HCs) manage the appointment systems and decide the appointed length of general practice consultation time This study aims at elucidating experienced PCNs' considerations in booking consultations of different lengths The grounds for giving long or short appointments were searched for Qualitative methods were used and 10 PCNs at eight HCs in Umeå Health District in northern Sweden were interviewed The PCNs take factors from two areas into consideration, one area, often immediately apparent, concerns immediate and straightforward issues such as the patient's reported problem, the patient her/himself, the doctor her/himself and the current situation at the HC and in the catchment area The other area for consideration usually develops through experience over the years and concerns time consumption in a longer perspective The overall quality of the consultations is then in focus and the length of a separate consultation is of minor interest The PCNs do not applicate a straightforward relation between length of time and quality of consultations Experienced PCNs seem to promote accessibility of primary care and their efforts in allocating time in a practical way probably increase the quality of general practice consultation     

Evidence for selective inhibition of limbic forebrain dopamine synthesis by 8-OH-DPAT in the rat

Summary Regional dopamine synthesis in the rat striatum was estimated by measuring DOPA accumulation following inhibition of cerebral aromatic l-amino acid decarboxylase by means of NSD-1015, 100 mg kg^–1 intraperitoneally. In animals treated with reserpine, 5 mg kg^–1 subcutaneously –18 h, there was a statistically significant increase in DOPA accumulation in the nucleus accumbens, the ventro-medial neostriatum, the dorso-lateral neostriatum and in the posterior limb of the neostriatum. This increase in DOPA accumulation was antagonized dose-dependently in the nucleus accumbens and ventro-medial neostriatum, but not in the other two regions, by treatment with the 5-HT_1A receptor agonist 8-OH-DPAT, 0.15–2.4 mol kg^–1, whereas the partial dopamine D₂ receptor agonist (–)3-PPP, 2.5–10.0 mol kg^–1, or the full dopamine D₂ receptor agonist quinpirole, 0.05–0.8 mol kg^–, antagonized the reserpine-induced increase in DOPA accumulation uniformly in all four regions of the striatum. The suppression of DOPA accumulation by 8-OH-DPAT in reserpine-treated animals, was completely antagonized by raclopride, 1 mol kg^–1, but not by (–)pindolol, 8 mol kg^–1. The accumulation of 5-HTP in all regions of the striatum as well as in the neocortex following decarboxylase inhibition and reserpine pretreatment, was also inhibited by 8-OH-DPAT, and this inhibition was unaffected by treatment with raclopride or (–)pindolol. It is concluded that 8-OH-DPAT, in addition to general effects on forebrain 5-hydroxytryptamine synthesis, selectively affects limbic forebrain dopamine synthesis. This latter effect is probably due to direct stimulation of dopamine autoreceptors, since it was obtained in reserpine-treated rats, and was completely antagonized by raclopride, but not (–)pindolol.Presented in part at the 7th General Meeting of the European Society for Neurochemistry, June 12–17th 1988, Göteborg, Sweden Send offprint requests to S. Ahlenius at the above address     

Role of the luxS quorum-sensing system in biofilm formation and virulence of Staphylococcus epidermidis

Nosocomial infections caused by Staphylococcus epidermidis are characterized by biofilm formation on implanted medical devices. Quorum-sensing regulation plays a major role in the biofilm development of many bacterial pathogens. Here, we describe luxS, a quorum-sensing system in staphylococci that has a significant impact on biofilm development and virulence. We constructed an isogenic DeltaluxS mutant strain of a biofilm-forming clinical isolate of S. epidermidis and demonstrated that luxS signaling is functional in S. epidermidis. The mutant strain showed increased biofilm formation in vitro and enhanced virulence in a rat model of biofilm-associated infection. Genetic complementation and addition of autoinducer 2-containing culture filtrate restored the wild-type phenotype, demonstrating that luxS repressed biofilm formation through a cell-cell signaling mechanism based on autoinducer 2 secretion. Enhanced production of the biofilm exopolysaccharide polysaccharide intercellular adhesin in the mutant strain is presumably the major cause of the observed phenotype. The agr quorum-sensing system has previously been shown to impact biofilm development and biofilm-associated infection in a way similar to that of luxS, although by regulation of different factors. Our study indicates a general scheme of quorum-sensing regulation of biofilm development in staphylococci, which contrasts with that observed in many other bacterial pathogens.