Dental treatment for people with cystic fibrosis.

AIM: To describe the nature and consequences of the multi-system genetic condition cystic fibrosis with a view to ensuring optimal dental treatment planning for these patients. METHODS: A literature search was conducted to identify the key medical and dental manifestations of cystic fibrosis. These findings are discussed and utilised to create recommendations for treatment planning in patients with cystic fibrosis for the practising dental practitioner. RESULTS: Cystic fibrosis is a complex, lethal, multisystem autosomal recessive disorder resulting from mutations on chromosome 7 which result in dysfunction of an ion channel that sits on epithelial surfaces. Respiratory disease remains the leading cause of mortality. Survival has greatly increased in recent decades secondary to improved treatment and specialist care. Specific dental manifestations of the disease may result from the condition itself or complications of treatment. Modification of patient management may be necessary to provide optimum patient care. CONCLUSION: The pathophysiology and clinical manifestations are relevant to practicing dental practitioners and inform recommendations to be utilised to ensure optimal treatment planning for these patients.

Enhanced cellular responses and environmental sampling within inner foreskin explants: implications for the foreskin's role in HIV transmission.

The decrease in HIV acquisition after circumcision suggests a role for the foreskin in HIV transmission. However, the mechanism leading to protection remains undefined. Using tissue explant cultures we found that Langerhans cells (LCs) in foreskin alter their cellular protein expression in response to external stimuli. Furthermore, we observe that upon treatment with TNF-alpha, tissue-resident LCs became activated and that stimulatory cytokines can specifically cause an influx of CD4+ T-cells into the epithelial layer. Importantly, both of these changes are significant in the inner, but not outer, foreskin. In addition, we find that LCs in the inner foreskin have increased ability to sample environmental proteins. These results suggest differences in permeability between the inner and outer foreskin and indicate that HIV target cells in the inner foreskin have increased interaction with external factors. This increased responsiveness and sampling provides novel insights into the underlying mechanism of how circumcision can decrease HIV transmission.

Micetoma / Mycetoma

Los micetomas son enfermedades caracterizadas por su intensa rebeldía y potencial discapacidad. Fueron descriptos como patología de origen fúngico, pero a través del tiempo algunos agentes cambiaron de clasificación y la definición, pasa entonces por la presencia de granos que contienen al agente en cuestión. La ausencia de tales granos puede definir al pseudomicetoma. Se comentan aspectos epidemiológicos de estos cuadros que suelen ser endémicos en muchos países. Asimismo se citan cuestiones acerca de tratamientos en el orden farmacológico, quirúrgico y aún de rehabilitación.

The mycetomas are diseases characterized by its intense rebellousness and potential disability. They were classified as pathology of fungicide origin, but across the time some agents changed classification and the definition happened then for the presence of grains that contains the agent. The absence of such grains can define the pseudomycetoma. Are commented epidemiological aspects of these diseases that are in the habit of being endemic in many countries. Also questions mention treatments in the orders pharmacological, surgically even of rehabilitation.

Clinical application of a rapid lung-orientated immunoassay in individuals with possible tuberculosis.

BACKGROUND: Immunological ex vivo assays to diagnose tuberculosis (TB) have great potential but have largely been blood-based and poorly evaluated in active TB. Lung sampling enables combined microbiological and immunological testing and uses higher frequency antigen-specific responses than in blood. METHODS: A prospective evaluation was undertaken of a flow cytometric assay measuring the percentage of interferon-gamma synthetic CD4+ lymphocytes following stimulation with purified protein derivative of Mycobacterium tuberculosis (PPD) in bronchoalveolar lavage fluid from 250 sputum smear-negative individuals with possible TB. A positive assay was defined as >1.5%. RESULTS: Of those who underwent lavage and were diagnosed with active TB, 95% (106/111) had a positive immunoassay (95% CI 89% to 98%). In 139 individuals deemed not to have active TB, 105 (76%) were immunoassay negative (95% CI 68% to 82%). Of the remaining 24% (34 cases) with a positive immunoassay, a substantial proportion had evidence of untreated TB; in two of these active TB was subsequently diagnosed. Assay performance was unaffected by HIV status, disease site or BCG vaccination. In culture-positive pulmonary cases, response to PPD was more sensitive than nucleic acid amplification testing (94% vs 73%). The use of early secretory antigen target-6 (ESAT-6) responses in 71 subjects was no better than PPD, and 19% of those with culture-confirmed TB and a positive PPD immunoassay had no detectable response to ESAT-6. CONCLUSIONS: These findings suggest that lung-orientated immunological investigation is a potentially powerful tool in diagnosing individuals with sputum smear-negative active TB, regardless of HIV serostatus.

Immune reconstitution pneumonitis following Pneumocystis carinii pneumonia in HIV-infected subjects.

An HIV-infected man presented with a pneumonic illness following an episode of treated Pneumocystis carinii pneumonia (PCP). He had a rise in his CD4 count from 4 to 125 cells/microL on antiretroviral therapy prior to the onset of the second respiratory event. Bronchoalveolar lavage (BAL) revealed no pathogen, although a CD4 lymphocytosis in addition to a highly unusual population of rapidly proliferating CD8 cells was demonstrated. Following 2 weeks of steroid and anti-pneumocystis therapy, a repeat bronchoscopy demonstrated that the expression of these markers had returned to low values. This second respiratory illness, which may have arisen as a consequence of the regenerating immune response reacting to residual P. carinii antigen in the lung, is apparently not rare. When we reviewed our case notes, five further individuals were identified that had started antiretroviral therapy following an episode of PCP and subsequently developed a self-limiting pneumonitis for which no pathogen was identified on bronchoscopy.

The changing demographics of new HIV diagnoses at a London centre from 1994 to 2000.

OBJECTIVE: To document the demographic changes in new HIV diagnoses at the Royal Free Hospital, London, UK, between 1994 and 2000. DESIGN: Retrospective case note review. METHODS: Data were extracted from the Royal Free HIV database identifying new diagnoses for 1994, 1997 and 2000. All case notes were reviewed and patients were included if they had their first positive HIV test at the Royal Free Hospital, or if they first tested positive elsewhere and attended the Royal Free HIV unit for their initial HIV care. Data extracted included sex, ethnicity, age, risk factor(s) for HIV, reason for test, clinical stage of disease, CD4 count and HIV RNA viral load at diagnosis. RESULTS: One hundred and forty-four patients were identified for 1994, 136 for 1997 and 110 for 2000. Over this time period the proportion of white patients dropped from 72% (n = 104) to 48% (n = 53), P = 0.0001, whilst the proportion of black Africans rose from 24% (n = 34) to 45% (n = 49), P = 0.0004. The median CD4 count at diagnosis of the white cohort was 475 cells/microL in 1994 and 286/microL in 2000, P = 0.005, whilst in the black African patients it was 240/microL and 230/microL for the same years. CONCLUSIONS: There has been a reduction in new HIV diagnoses among the white population and a rise in the black Africans at this centre between 1994 and 2000. The clinical and immunological parameters of HIV disease have worsened over this time period for the white group, but have remained stable in the black Africans.

Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited.

Various hypotheses have been proposed to explain why cytomegalovirus pneumonitis (CMV-P) is frequent and severe in bone marrow transplant patients while remaining rare and mild in HIV infected patients. One hypothesis suggests that CMV-P is an immunopathological condition that is common in bone marrow transplantation (BMT) under the effects of an abnormally regenerating immune system that reacts against CMV infected lung tissue. Such a hypothesis implicates CD4 T lymphocytes as one of the critical cell populations involved in immunopathology and also suggests that this process would be aborted by CD4 T cell deficiency in HIV infection. However, studies correlating the onset of CMV-P with lymphocyte reconstitution following BMT have revealed that CD4 cells are present at very low frequencies in the blood during the early period after transplantation when most cases of CMV-P occur. Furthermore, studies directly investigating bronchoalveolar lavage cell types during episodes of CMV-P in BMT patients have also failed to demonstrate significant CD4 involvement and, instead, have emphasized a predominance of natural killer (NK) cells and CD8 cells. These findings serve as the basis for questioning the validity of a CD4-driven immunopathological model of CMV-P in BMT. On the other hand, a variety of experimental and clinical observations support the protective role of CMV-specific CD3+ CD8 T lymphocytes against CMV in both immunocompetent individuals and BMT patients. In a murine BMT model, adoptive transfer of syngeneic BM cells was associated with massive increases in lung CD8 cells which resulted in the resolution rather than the exacerbation of existing CMV-P. In the light of these findings a more plausible hypothesis for CMV-P in BMT is that during the early period after transplantation adequate protective CD8 responses are absent and an uncontrolled CMV proliferation is allowed to develop. Once a critical viral load is reached a cytokine 'storm' may be triggered in the lung tissue that aggravates direct CMV-associated cytopathic effects. Likely candidates for this process would include the release of tumour necrosis factor-alpha (TNF-alpha) from alveolar macrophages stimulated by interferon-gamma (IFN-gamma) released from NK cells that are reconstituted early after BMT.

Respiratory infections in immunocompromised patients.

HIV disease has been dramatically reduced in the developed world by the introduction of highly active antiretroviral therapy, with implications that prophylactic therapy against opportunistic infections may be stopped; however, tuberculosis is an escalating problem in the HIV-infected and HIV-noninfected populations worldwide. Compliance with effective treatment regimens, especially through directly observed therapy, remains the cornerstone of tuberculosis control strategies. Although tuberculosis prophylaxis is of benefit for tuberculin skin reactors with HIV in the developed world, several reservations are voiced about this approach in resource-poor settings. Recent advances in technology, particularly in antigen-specific systems, have revolutionized the understanding of HIV immunology and helped to elucidate the mechanisms of pathogenesis in diseases such as cytomegalovirus. In bone marrow transplantation and solid-organ transplantation patients, quantitative polymerase chain reaction (PCR) to predict cytomegalovirus disease is an important advance, and patients who undergo bone marrow transplantation, CT scanning has proven useful in the diagnosis of pulmonary aspergillosis.

Variation in fold vibration during voiced obstruents in Russian.

A laryngographic analysis was carried out of vocal fold vibration produced during the supraglottal constriction for fricatives and stops. The subjects were a group of Russian speakers with normal voice production. Differences in vocal fold behaviour within this group of normal speakers were investigated. Changes in vocal fold vibration occurring during voiced fricatives and stops were evident from the Laryngograph waveform. Interpretation of the Lx waveform patterns suggests that partial opening of the vocal folds through the vibratory cycle may occur in some tokens. The evidence for this particular vocal fold behaviour remains inconclusive, however. Variations in vibratory patterns were found both between speakers and between utterances from individual speakers.

Muscle and joint pain: design and evaluation of courses for general practitioners.

Existing deficiencies in general practice management of rheumatic disease are identified and the evolution of a three-day course designed to remedy these deficiencies is described. Evaluation of the courses showed changes in the performance of participants in diagnosing and treating rheumatic disorders. Knowledge was increased, referral to hospital was halved and treatments in general practice, such as injections of steroids and advice on self-care, were increased. These changes were measured and were maintained up to two years after the course.