[Fertility preservation among patients with cancer: report of a French regional practical experience]. / Préservation de la fertilité en oncologie : bilan des pratiques en Région PACA-Corse.

OBJECTIVE: Improvement in cancer treatments has led to reconsider the importance of quality of life after cancer, especially concerning maintening the potential of fertility since it is often altered after healing. Our objective was to estimate the knowledge and practices of the physicians in the field of Oncology in a French Region (Provence Alpes- Côte d'Azur). PATIENTS AND METHOD: Prospective survey, conducted between January and April 2012, amongst oncologists working in Provence Alpes Côte d'Azur region, through questionnaires distributed during multidisciplinary meetings in oncology. RESULTS: Among 225 replies, 54% of the physicians had sent no patient to any oncofertility consultation during the previous six months (n=120). Besides, 33% of the oncologists (n=68) declared they had difficulties in addressing their patients to oncofertility consultation, and 58% of them (n=39) considered they lacked information on techniques and indications of fertility preservation. CONCLUSION: This study provides an estimation of the current practices in PACA region concerning oncofertility and underlines the physicians' need of information. In this context, the regional oncology network has set up a regional network « cancer and fertility ¼ in order to facilitate the access to fertility preservation prior to any potentially sterilizing treatment for all patients.

Nelfinavir in HIV-HCV coinfected patients: a 24-month follow-up in a cohort of 82 patients.

This retrospective and longitudinal study evaluated the long-term hepatic tolerance of a nelfinavir (NFV)-antiretroviral combined regimen in 82 patients of the HCV-HIV Cohort of CISIH-Sud of Marseilles. Follow-up data (liver enzyme levels, CD4 cell count, HIV viral load, and metabolic parameters) of patients treated with NFV on inclusion or during the follow-up of the cohort were analyzed under treatment over 24 months. Comparisons were performed with X2 or Kruskal-Wallis tests. At baseline (n = 82), the median exposure to NFV was 4.1 months; 58 patients received NFV combined with NRTI and 24 with NNRTI. The median CD4 cell count was 337/mm3 [interquartile range (IR): 216-480) and 39.7% had an undetectable HIV RNA level. Qualitative HCV PCR was positive in 91% of the patients and 19/51 patients with liver biopsy were F3-F4. Median alanine and aspartate aminotransferase (ALAT, ASAT), gamma-glutamyltransferase (GT), and alkaline phosphatase (ALP) were 46 UI/liter (IR: 36-76), 55 UI/liter (IR: 32-97), 97 UI/liter (IR: 50-194), and 88 UI/liter (IR: 72-104), respectively, with 76% of the patients with ALAT/ASAT grade <2. Median follow-up was 23 months (IR: 13.8-37). No significant difference was observed in the distribution of ALAT, ASAT, GT, and ALP as well as of ALAT/ASAT grades over the 24-month study period. Patients treated with NFV + NNRTI had significantly higher GT and ALP levels at baseline with no significant increase during follow-up. Cholesterol, triglyceride, and glycemia distributions remained stable over time. In conclusion, this study showed a good hepatic and metabolic tolerance of a long-term NFV-combined regimen in HIV-HCV coinfected patients.

Reduction of oral acetaldehyde levels using a controlled-release chlorhexidine chip as a prevention strategy against upper digestive tract cancer.

Increasing evidence indicates a strong relationship exists between harmful habits like smoking and alcohol drinking and upper digestive tract cancer. In addition, smokers and alcohol drinkers also exhibit high salivary levels of carcinogenic acetaldehyde, the first metabolite of alcohol. This compound has been indicated as a major cancer causing factor in the upper digestive tract, especially among alcohol drinkers. Interestingly, acetaldehyde is produced from alcohol present in the epithelia by mucosal alcohol dehydrogenases (ADH) in the upper digestive tract. However, much higher levels derive from the bacterial oxidation of alcohol by the oral microflora. In this respect, the reduction of oral microbes can become a fundamental factor in diminishing the risk of cancer. In this article, we hypothesize that the antimicrobial agent chlorhexidine, formulated as controlled-release chip, and fixed by a dental device, (i.e., a modified orthodontic bracket), may be the most rational strategy for reducing acetaldehyde production by microflora.

The volatile fraction of cigarette smoke induces alterations in the human gingival fibroblast cytoskeleton.

Several in vitro investigations have indicated that the particulate phase of cigarette smoke, such as nicotine, affects many cell types, including gingival fibroblasts. However, few studies have been performed on the effects of the volatile fraction on the cellular structures that are involved in cell functions, such as adhesion and proliferation. Since the survival and reproduction of gingival fibroblasts are fundamental in maintaining the integrity of the oral connective tissue, as well as in wound healing, the effects on the cytoskeleton of acrolein and acetaldehyde, which are the volatile fractions of cigarette smoke, were examined in vitro for human gingival fibroblasts (HGFs). HGF strains that were taken from healthy subjects with non-inflamed-gingiva were utilized in this investigation. The cells were incubated in the presence of different concentrations of acrolein and acetaldehyde. Cell adhesion and viability were evaluated after incubation for 3 h and 5 days, respectively. The influence on cytoskeletal structures (tubulin, actin and vimentin intermediate filaments) was investigated with the indirect immunofluorescence technique. The results show that both substances produced similar effects, which resulted in a dose-dependent inhibition of HGF adhesion and viability. Disturbance of the HGF cytoskeleton consisted of disruption of the microtubules, actin filaments and vimentin microfilaments, which was accompanied by alterations to cell shape. Our experimental findings suggest that the volatile fractions of cigarette smoke, such as acrolein and acetaldehyde, have a cytotoxic effect on HGFs, with the result that they lose their capacity for adhesion and proliferation. The consequences of this could be impairment of the maintenance, integrity and remodelling of the oral connective tissue. According to our morphological evidence, these findings show that cigarette smoke can lead to the development and progression of periodontal disease, and indicate the need for appropriate therapy.

Human gingival fibroblast cytoskeleton is a target for volatile smoke components.

BACKGROUND: Several in vitro investigations have indicated that the particulate phase of cigarette smoke as nicotine affects many cell types including gingival fibroblasts, but few studies have examined the effect of volatile fraction on cellular structures involved in cell functions such as adhesion and proliferation. Since gingival fibroblast survival and reproduction are fundamental to maintaining the oral connective tissue as well as to wound healing, the effects of acrolein and acetaldehyde, volatile fractions of cigarette smoke, on cytoskeleton were examined in human gingival fibroblasts (HGFs) in vitro. METHODS: Human gingival fibroblast (HGF) strains from healthy subjects with non-inflamed gingiva were utilized. The cells were incubated in different concentrations of acrolein and acetaldehyde. Cell adhesion was evaluated after 3 hours. The influence of both substances on cytoskeletal structures, tubulin and vimentin intermediate filaments (VIF), was investigated using indirect immunofluorescence technique. RESULTS: The results show that both substances produced similar effects, resulting in a dose-dependent inhibition of HGF adhesion. Disturbance of HGF cytoskeleton consisted of a disruption of microtubules and vimentin microfilaments with alterations in cell shape. CONCLUSIONS: Our experimental findings suggest that volatile fractions of cigarette smoke such as acrolein and acetaldehyde, because their ability to bind and interact with the cytoskeleton, prevent HGF adhesion. Consequently the maintenance of the oral connective tissue and integrity and remodeling could be impaired. According to our morphological evidence, these findings confirm other clinical and epidemiological investigations reporting that volatile components of cigarette smoke could lead to the initiation and progression of periodontal disease.

Microtubules and vimentin associated filaments (VIFs) in cultured human gingival fibroblasts (HGFs) after exposure to acrolein and acetaldehyde.

Tobacco smoke, particularly its non-volatile fraction e. g. nicotine, is considered to be a major risk factor for the development and progression of periodontal disease. The purpose of this study has been to determine the effects of acrolein and acetaldehyde of the volatile fraction of tobacco smoking, on human gingival fibroblasts (HGFs) cultured in vitro with particular attention to cytoskeletal structures. A human gingival fibroblast strain derived from healthy gingiva was utilized in this study. The cells were exposed to acrolein and acetaldehyde at various concentrations. Control and treated cells were compared as regards their adhesion on cell culture dishes. Their cytoskeletal structures [tubulin and vimentin intermediate filaments (VIFs)] were examined by fluorescence microscopy. The results revealed that both substances produced similar effects resulting in a dose dependent decrease in cell adhesion and alterations of HGF cytoskeleton consisting of rearrangement and/or disruption of microtubules and vimentin associated filaments. Changes in cell shape and decrease in cell size were also seen. On the basis of this in vitro study, it appears that tobacco, through its volatile components, may directly affect the main functions of HGFs.

Ultrastructural changes in human gingival fibroblasts in vitro after exposure to vapour phase smoke components.

Tobacco and some of its volatile and non-volatile components have been found to affect many types of cells including gingival fibroblasts. Because normal gingival fibroblast functioning is fundamental to the maintenance of the oral connective tissue as well as to wound healing, we examined the effect of two vapour phase smoke components (acrolein and acetaldehyde) on proliferation and ultrastructure of human gingival fibroblasts (HGFs) in culture. A human gingival fibroblast strain derived from healthy individuals was used in this study. The cells were incubated in the presence of different concentrations of acrolein and acetaldehyde and cell proliferation and fine morphology were evaluated. The results show that acrolein and acetaldehyde produced dose dependent inhibition of HGF viability and alteration of cytoplasmic organelles. The main ultrastructural finding for the HGF cytoplasm was the presence of vacuoles and lysosomal structures which became prominent with increasing concentration of acrolein and acetaldehyde. Our results suggest that the ultrastructural alterations we observed in HGFs may be due to the uptake and storage of acrolein and acetaldehyde by the cells.

Volatile components of cigarette smoke: effect of acrolein and acetaldehyde on human gingival fibroblasts in vitro.

BACKGROUND: Tobacco and some of its volatile and non-volatile components have been found to affect many types of cells including gingival fibroblasts. Since normal gingival fibroblast functioning is fundamental to the maintenance of the periodontal connective tissue, as well as to wound healing, we examined the effect of acrolein and acetaldehyde, volatile components of cigarette smoke, on proliferation, attachment, and ultrastructure of human gingival fibroblasts (HGFs) in culture. METHODS: Human gingival fibroblast (HGF) strains derived from healthy individuals with non-inflamed gingiva were used in this study. The cells were incubated in the presence of different concentrations of acrolein and acetaldehyde. Cell attachment and proliferation were evaluated after incubation for 3 hours and 5 days, respectively. In addition, the cells were examined with a transmission electron microscope in order to evaluate their morphology. RESULTS: The results show that acrolein and acetaldehyde produced dose-dependent inhibition of HGF attachment and proliferation. The cytotoxic effect was, however, reversible when both substances were removed, after 3 days, from the medium. The main ultrastructural finding for the HGF cytoplasm was the presence of vacuoles and lysosomal structures that became prominent with increasing concentration of acrolein and acetaldehyde. CONCLUSIONS: Our experimental data suggest that acrolein and acetaldehyde, volatile components of tobacco smoke, are detrimental to HGF survival and consequently to the oral connective tissue. According to our morpho-functional evidence, these findings corroborate clinical and epidemiological investigations demonstrating smoke as a risk factor in the development of periodontal disease.

Tobacco smoke in the development and therapy of periodontal disease: progress and questions.

In recent years, epidemiological studies have pointed to a significant correlation between cigarette smoke and poor periodontal status. Cigarette smoking is a significant risk factor for the onset and development of periodontal disease, and an association between reduced healing response subsequent to periodontal therapies and cigarette smoking has been found. The epidemiological studies reported here are also supported by the results of an in vitro study on the cytotoxicity of two of the volatile components of cigarette smoke that we ourselves conducted, in which the investigated compounds were found to damage human gingival fibroblasts. We concluded that this damage would be reflected in periodontal health and could slow down wound healing. Patients should thus be alerted by clinicians to the risks smoking poses to oral and dental health.

Structure of the initial lymphatics of the human urinary bladder with invasive urothelial tumors.

The ability of urothelial tumors of the urinary bladder to metastasize via the lymphatic circulation and the extent of metastatic involvement of regional lymph nodes is an important parameter in the staging and prognosis of these neoplasms. Accordingly, we examined the site and morphology of initial lymphatic vessels in the mucosa of the human urinary bladder in patients with invasive transitional cell carcinoma. Lymphatics in the papillary tumoral mass was also examined. Endoscopic transurethral biopsies from the urinary bladder of 120 patients with invasive transitional cell papillary carcinoma were utilized for this study. Biopsy from the uninvolved lateral wall of the same patient was utilized as a control. On histopathology of biopsies of neoplastic tissues, initial lymph vessels were seen in the deeper region of the mucosa but not in the subepithelial layer nor in the stroma of the tumoral papillae. The latter were often associated with arteriolar and venular vessels. When edema and inflammation occurred in peritumoral regions, lymphatics showed a dilated lumen, non-indented wall with dissociated perivascular collagen and elastic fibers. Tumoral permeation or embolization of lymphatics was seen in 12% of patients with invasive tumors, and these lymphatic vessels did not display significant morphologic changes. The absence of initial lymphatics in the stroma of tumoral papillae and in infiltrated subepithelial regions of the urinary bladder may explain the absence of lymph node metastasis in early-stage invasive urothelial tumors.

Morphological changes of dermal blood and lymphatic vessels in chronic venous insufficiency of the leg.

Morphological changes of dermal blood and lymphatic microcirculation in skin biopsies from patients affected by Chronic Venous Insufficiency (CVI) associated with stasis dermatitis of the lower limbs, are reported here. Blood vessels are characterized by an occluded lumen, thickening and reduplication of the basement membrane. The structural changes in dermal lymphatic vessels are: (i) collapsed lumen of lymphatics located in the papillar dermis; (ii) numerous and complex interdigitations between contiguous endothelial cells and lack of open junctions; (iii) derangement of the anchoring filaments that normally pull the lymphatic lumen open. The connective matrix is characterized by fibrosis with formation of dense bundles of collagen and elastic fibers. These results suggest that the dermal lymphatic and blood microcirculation in CVI are connected to a reduced fluid exchange capacity because of the structural changes occurred in the vascular and lymphatic wall and in the surrounding connective tissue.

[Neuroradiology of infective diseases in the immunocompromised host]. / La neuroradiologia delle malattie infettive nella immunodepressione.

Just like the lung, the brain and the spinal cord are target organs for opportunistic infections and tumors in immunocompromised patients. HIV infections and AIDS-related conditions represent the most common cause of immunodeficiency: other causes are hemoproliferative disorders and organ transplantation, but especially long-term drug and radiation therapies. Neurologic (focal, diffuse, meningeal or spinal) signs are the results of CNS infections and/or tumors or of treatment complications. Neuroimaging techniques (MRI better than CT) allow the infective or neoplastic causes of neurologic complications to be nearly always recognized and are therefore major tools for diagnosis and treatment. Lesions characterization is more difficult, since CT and MR patterns are definitely more affected by the evolutive phases of the lesions (encephalitis, cerebritis, abscess) and by their sites than by specific infective agents. However, the knowledge of the statistical possibility of brain and spine infections according to the type of immunocompromission is useful in many cases.

[Stress myocardial scintigraphy in the pre- and postoperative diagnosis of ischemic cardiopathy. The correlations between the clinical aspects and the coronary angiographic picture]. / La scintigrafia miocardica da sforzo nella diagnostica pre- e postoperatoria della cardiopatia ischemia. Correlazioni tra aspetti clinici e quadri coronarografici.

With radioisotopes it is possible to study the heart obtaining complementary or substitutive informations to those provided by the most common noninvasive methods of myocardial assessment and by coronarography. This paper aim is to report experience with thallium 201 and 99mTc isonitrile in the diagnosis and followup of ischemic heart disease, in particular correlating clinical, coronarographic and scintigraphic findings. MATERIAL AND METHODS. During the biennium 1989-91 we have used the myocardial perfusion imaging with thallium 201 in 29 patients (20 male age ranging from 40 to 60 years) injecting 2 mCi at exercise peak with immediate planar mapping, followed by a second registration at rest 4 hours later (thallium 201). Imaging with 99mTc SESTAMIBI has been carried out in 6 patients (two of whom previously studied with thallium 201) injecting 20-22 mCi both at stress peak and at rest, with SPECT mapping 60'-90' later. All these patients presented specific problems for the diagnosis of myocardial ischemia. The exercise testing has been performed by a bicycle ergometer and with a standardized procedure increasing every two minutes the workload to the maximum tolerated according to the clinical conditions and to the response. All antianginal treatments were discontinued for at least 48 hours before testing and the patients were fasted for 6 hours. The images were obtained using a small field scintillation camera with a low-energy general purpose collimator. We divided the patients in 4 groups: Group A. Six patients who had an open heart operation: in 5 coronary revascularization was carried out (plus left ventricular aneurysmectomy in one and plus aortic valve replacement in another); in 1 patient an aortic valve replacement was performed on. Group B. Six patients have been evaluated after coronary angiography. Group C. Seventeen patients with doubtful diagnosis of myocardial ischemia on the base of the symptoms and/or non invasive testing as rest or stress electrocardiogram (ECG). Group D. In 6 more patients (2 of those previously studied with thallium 201) the myocardium has been assessed with SESTAMIBI. RESULTS. In one patient of the group A the thallium 201 images detected silent ischemia; in 5 removed the diagnostic doubts of the ECG findings owing to left ventricular overload or to old infarctions in 2 patients and to electrolytes disturbances or pharmacological effects in 3 patients. In group B patients the thallium 201 further on could assess the extent of ischemic and necrotic areas suggesting the final indications to angioplasty in 3 patients, medical treatment in 2 and surgery in 1. We could not find correlations between the extent of the disease predicted by the coronarography and the findings of the thallium 201 images. In the diagnosis of myocardial ischemia, group C, the Thallium 201 has been very useful and specific excluding an ischemic origin in 4 patients with arrhythmias, in 2 patients without symptoms of angina but with doubts at rest and exercise ECG findings and in 4 with atypical thoracoalgia and doubtful ECG. On the contrary, this test could give the final diagnosis of ischemia in 6 patients displaying its sensitivity in detecting coronary artery disease. Among the patients assessed with SESTAMIBI, in 2 this test has been essential in evaluating the myocardial contractility and the segmental wall motion. DISCUSSION. The usefulness of Thallium 201 imaging, as a very sensitive mean in detecting coronary artery disease and in the assessment of myocardial viability, is well known. Although the most common indications of this technique are well standardized, in the clinical practice there are many situations in which the thallium 201 can contribute to the diagnosis and to the management. (ABSTRACT TRUNCATED)

[Shoulder instability and pain. Computerized arthro-tomography assessment]. / Spalla instabile e dolorosa. Valutazione con artro-tomografia computerizzata.

The growing interest in shoulder joint imaging comes from the ever-increasing demand for such an examination in orthopedics. Since more complete and detailed imaging of bone, capsuloligamentous and musculotendinous compartments is always needed, CT arthrography has necessarily become a widely used method. In this study, 282 patients were investigated with CT arthrography. Seventy per cent of them had anatomical instability, 17.3% had functional instability and the extant 12.7% had shoulder pain. In traumatic instability, the most often injured structures were the glenoid labra (91%) and the capsule (82%). Lesions in the two structures were nearly always associated. Moreover, high incidence (65.8%) of Hill-Sachs lesions of the humeral head was observed. In atraumatic instability, abnormal anteversion of the scapular glenoid was always detected. In the patients with shoulder pain, the most common causes were the impingement syndrome (30.5%), superior labrum lesions (16.7%), adhesive capsulitis (16.7%) and synovial osteochondromatosis (13.7%). With CT arthrography, labial abnormalities (detachments, tears, amputations, eversions and degeneration) can be identified, as well as capsular lesions (insertional detachment and laxity), rotator cuff conditions (bursitis, tendinitis and partial/complete tears), biceps tendon abnormalities and glenoid rim and humeral head fractures. Moreover, CT arthrography is minimally invasive and well tolerated. It exhibits 97.7% specificity, 91% sensitivity and 96% accuracy. Furthermore, it has been proven to be extremely useful in treatment and surgical planning.

Immunohistochemical localization of endothelin-like immunoreactivity in human tooth germ and mature dental pulp.

The distribution in oral tissues of endothelin, a multifunctional peptide originally identified within endothelial cells, and subsequently in some epithelial cells, neurons and neuroendocrine cells, has not been investigated yet. We have studied the localization of endothelin-like immunoreactivity in human tooth germ and mature dental pulp by immunohistochemical techniques. Such immunoreactivity was detected only within endothelial cells in both mature dental pulp and developing tooth. Arteries and veins of various sizes as well as small thin vessels displayed endothelin-like immunoreactivity. In the tooth germ, the cells of the enamel organ or the precursors of the odontoblasts were found unreactive. In the mature pulp, no cells of the stroma or nerves displayed endothelin-like immunoreactivity. These findings suggest that vascular endothelium may be the only source of endothelin in human dental tissues. It is tentatively proposed that endothelin released in mature tooth pulp may participate in the regulation of the pulpal blood flow. Although the possible role of endothelin in developing tissues is far from being clear, the mitogenic effects and the proto-oncogenes expression induced by endothelin in some cells raise the possibility that this peptide might also play a role during tooth development.

Prevention of doxorubicin-induced cardiomyopathy by reduced glutathione.

The aim of the present investigation was to evaluate the potential cardioprotective effect of reduced glutathione (GSH) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a well-documented rat model. DXR was administered i.v. at a weekly dose of 3 mg/kg for a total of 4 doses; 250 or 500 mg/kg of GSH was given i.v. 10 min before and 2 h after each DXR injection, resulting in a total weekly dose of 500 or 1000 mg/kg, respectively. The development of cardiotoxicity was monitored in vivo by means of electrocardiography (QaT duration), and was evaluated by measuring the contractile performance of isolated atria and by light and electron microscopy of left ventricular samples excised 5 weeks after the last DXR administration. DXR was found to impair body weight gain and to produce an irreversible and time-dependent prolongation of QaT, a decrease in myocardial contractility of isolated atria and typical morphologic alterations, including myocyte vacuolization and myofibrillar loss. Pretreatment with GSH at a dose of 500 mg/kg x 2, but not at 250 mg/kg x 2, partially prevented the impairment of body weight gain, QaT prolongation in ECG and the decrease in myocardial contractility of isolated atria induced by DXR. Alterations of the morphologic pattern were also significantly reduced in animals receiving the higher dose of GSH. Determinations of the cardiac non-protein sulfhydryl group content showed that GSH, at doses higher than or equal to 500 mg/kg, significantly increased this parameter, irrespective of the presence of DXR. In conclusion, the present data indirectly support the hypothesis that oxidative damage is involved in DXR cardiotoxicity and indicate that maintenance of the reduced thiol pool could be an important issue in myocardial protection.

Acquired rod-body myopathy associated with human immunodeficiency virus infection.

A 35 year old homosexual man showed clinical features of myopathy, with progressive muscular weakness of proximal muscles. EMG demonstrated a myopathic pattern; serum CPK was mildly elevated and CSF examination revealed antibodies to HIV and a blood-brain barrier damage. An open biopsy of the quadriceps femoris muscle showed myopathic changes with inflammatory features including a marked variation in fiber size, necrotic fibers and phagocytosis, a profusion of internal nuclei. Fiber type analysis with myosin ATPase reaction revealed that myopathic changes involved both fiber types. Changes in the oxidative enzyme activities were also observed in the degenerating muscle fibers. Electron microscopy showed patterns of myofibrillar degeneration and characteristic rod bodies in 30% of fibers. The close resemblance of the present morphological results with those recently observed in some HIV antibody positive men seems to indicate the existence of a specific structural myopathy associated with AIDS.