Assessment of aldehyde dehydrogenase in viable cells

Cytosolic aldehyde dehydrogenase (ALDH), an enzyme responsible for oxidizing intracellular aldehydes, has an important role in ethanol, vitamin A, and cyclophosphamide metabolism. High expression of this enzyme in primitive stem cells from multiple tissues, including bone marrow and intestine, appears to be an important mechanism by which these cells are resistant to cyclophosphamide. However, although hematopoietic stem cells (HSC) express high levels of cytosolic ALDH, isolating viable HSC by their ALDH expression has not been possible because ALDH is an intracellular protein. We found that a fluorescent aldehyde, dansyl aminoacetaldehyde (DAAA), could be used in flow cytometry experiments to isolate viable mouse and human cells based on their ALDH content. The level of dansyl fluorescence exhibited by cells after incubation with DAAA paralleled cytosolic ALDH levels determined by Western blotting and the sensitivity of the cells to cyclophosphamide. Moreover, DAAA appeared to be a more sensitive means of assessing cytosolic ALDH levels than Western blotting. Bone marrow progenitors treated with DAAA proliferated normally. Furthermore, marrow cells expressing high levels of dansyl fluorescence after incubation with DAAA were enriched for hematopoietic progenitors. The ability to isolate viable cells that express high levels of cytosolic ALDH could be an important component of methodology for identifying and purifying HSC and for studying cyclophosphamide-resistant tumor cell populations.     

Anal intraepithelial neoplasia and squamous cell carcinoma in HIV‐infected adults

Anal cancer is one of the most common non‐AIDS‐defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV‐infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV‐related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV‐infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV‐infected adults.     

Wound infection,dressings and pain,is there a relationship in the chronic wound?

The focus on quality of life issues in wound care has justly taken a far greater importance. With the acceptance that pain can be a major factor to the patient, and in particular, pain at dressing change comes the opportunity for avoidance and/or reduction strategies. Whilst pain has been associated with wound infection for millennia, it is only much more recently that this has received due attention from research and clinical practice. In this study, the nature of pain, changes in pain and pain associated with infection are the focal points. A Delphi approach, now a frequently used tool in wound care research, has been used to obtain expert opinion on these aspects of management.     

The cross‐pin retained implant supported restoration: a study of gasket placement and leakage

Background: Advantages of cross‐pin retained implant supported restorations (ISRs) include predictable retrieval and predictable retention. Unlike direct to fixture (DTF) or cement retained restorations, the prosthetic design of a cross‐pinned restoration retains gaps at the interfaces between the crown, abutment and cross‐pin screw. These spaces permit leakage into the suprastructure and gasket placement has been recommended to prevent this leakage. Methods: Five different gaskets were assessed for their ability to prevent leakage into a cross‐pinned ISR. The gaskets tested were: cement admixture on the cross‐pin screw; cement admixture on the inner surface of the coping and the cross‐pin screw; cement admixture on the inner surface of the coping only; cement admixture placed 1 mm from the margin of the coping and a filler placed in the abutment chimney. Results: Only gaskets which sealed both the cross‐pin screw interface and the abutment‐crown interface prevented leakage. A filler placed in the abutment chimney prevented leakage into this space but did not prevent fluid accumulating between the coping and abutment. Conservative placement of cement at the margin of the coping failed to prevent leakage. Conclusions: Cement gaskets may effectively prevent leakage into a cross‐pinned ISR. However, the use of a cement as a gasket has to be weighed against the issue of predictable retrieval, cement extrusion and incomplete seating.     

Helicobacter pylori infection treatment of nonulcer dyspepsia: an analysis of meta-analyses

BACKGROUND: Meta-analysis is often used to resolve uncertainty in magnitude of effect between studies. However, several meta-analyses investigating the association between Helicobacter pylori infection and nonulcer dyspepsia reported contradictory results. GOALS: To perform a systematic review of the conflicting data in meta-analyses examining the association between H. pylori infection and nonulcer dyspepsia. STUDY: Five meta-analyses were identified: three studied the relation between H. pylori treatment and nonulcer dyspepsia, one studied the relation between H. pylori eradication and nonulcer dyspepsia, and one reported both. Data on search strategy, study selection, study inclusion, data abstraction, reported results of included studies, and summarized effect estimates were collected. RESULTS: Overall, 29 studies were included in the five meta-analyses. Nine studies (31%) were evaluated in more than one meta-analysis. There was no disagreement between the meta-analyses concerning the interpretation of outcome per investigated study; the results from seven (24%) studies showed improvement of dyspeptic symptoms after H. pylori treatment or eradication. The odds ratio of symptom relief in the control groups relative to the treated groups varied between 0.30 (95% CI = 0.2-0.5) to 0.88 (95% CI = 0.7-1.2). The proportion of patients' symptom free due to H. pylori treatment varied between 11% and 38%. CONCLUSIONS: The reported conflicting results between the meta-analyses were mainly a result of differences in study selection (eligibility and quality criteria) and relatively small. In a subgroup of patients with nonulcer dyspepsia, H. pylori eradication is useful for relief of symptoms.     

Orofacial neuralgia associated with a middle cerebral artery aneurysm

Chronic orofacial pain of neuropathic origin can present diagnostic and management dilemmas to dental practitioners and also affects the patient's quality of life. Intracranial aneurysms are a potential cause of stroke (e.g. sub‐arachnoid haemorrhage) that is usually associated with, high rates of mortality and morbidity. A patient who had been previously managed for symptoms of temporomandibular joint disorder (TMD) presented with sharp, shooting pain of moderate intensity. It was precipitated by swallowing, and radiated to the right throat, posterior border of the mandible, ear and temporomandibular joint. Clinical and radiological investigations ruled out odontogenic pain, TMD and other more common types of facial pain. Magnetic resonance imaging revealed a 7 × 6 mm aneurysm in the right middle cerebral artery (MCA) which was subsequently surgically clipped. Interestingly, the facial pain resolved after this procedure. Compression of the insular region of the brain innervated by the trigeminal, glossopharyngeal and vagus nerves provides a plausible explanation for the pain reported. To our knowledge, this is the first case of facial neuralgia associated with an aneurysm in the MCA which emphasizes the importance of a multidisciplinary approach in the diagnosis and management of unusual cases of chronic orofacial pain.     

The influence of pretreatment on cure rates of Helicobacter pylori eradication

BACKGROUND: Many patients treated for H. pylori infection have been taking a proton pump inhibitor beforehand. There is conflicting evidence whether pretreatment influences the efficacy of H. pylori eradication. The aim of this study was to investigate the influence of pretreatment on cure rates of H. pylori eradication. METHODS: Patients with H. pylori positive peptic ulcer disease or functional dyspepsia were treated with two-day quadruple therapy (lansoprazole 30 mg twice daily, and colloidal bismuth subcitrate 120 mg, tetracycline 250 mg and metronidazole 250 mg, all eight times a day). Patients were randomised to receive either three-day pretreatment with lansoprazole 30 mg twice daily or no pretreatment. H. pylori was diagnosed using CLO, histology and culture. RESULTS: Twenty-five (66%) of 38 patients with pretreatment and 32 (84%) of 38 patients without pretreatment were cured (p=0.06). After adjustment for diagnosis, smoking status and metronidazole resistance the influence of pretreatment became slightly less pronounced (OR 0.44, 95% CI 0.1-1.7). Nonsmokers and patients with peptic ulcer disease were more likely to achieve H. pylori eradication than smokers and patients with functional dyspepsia, respectively (adjusted odds ratios: 4.79 (1.2-19) and 4.32 (1.0-18)). CONCLUSIONS: This two-day quadruple therapy reached an overall cure rate of 75%. Nonsmokers and patients with peptic ulcer disease were more likely to achieve H. pylori eradication. Three-day pretreatment with a proton pump inhibitor may decrease cure rates of this two-day quadruple therapy.