[Polymyositis with antisynthetase syndrome and cardiac involvement].
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Autoantibodies↗
Biomedical subjects
M Younes
Publications and source records attributed to M Younes.
Expression of GCDFP-15 and AR decreases in larger or node-positive apocrine carcinomas of the breast.
AIMS: Apocrine carcinoma of the breast is typically, though not always, positive for gross cystic disease fluid protein-15 (GCDFP-15). In order to clarify the clinical significance of GCDFP-15 in apocrine carcinomas, GCDFP-15 expression was examined in apocrine carcinomas of different stages and compared with clinicopathological factors. Apocrine lesions reportedly exhibit an unusual immunohistochemical status, expressing androgen receptors (AR) instead of oestrogen receptors (ER), progesterone receptors (PR), or bcl-2. Their expression was also examined. METHODS AND RESULTS: Fifty-two apocrine carcinomas were examined immunohistochemically. Thirty-nine (75%) and 29 (56%) were positive for GCDFP-15 and AR, respectively. GCDFP-15 positivity was significantly lower in infiltrating carcinomas than intraductal carcinomas (P = 0.0111). In infiltrating carcinomas, GCDFP-15 positivity was significantly low in tumours > or = 15 mm (P = 0.0005) and node-positive tumours (P = 0.0004). Similar phenomena were observed for AR. Rare cases were positive for ER (3.8%), PR (5.8%), and bcl-2 (1.9%). CONCLUSIONS: GCDFP-15 positivity is transient and should not be considered a definitive marker of apocrine carcinomas. Cases which have apocrine features but lack GCDFP-15 expression should rather be considered as advanced apocrine carcinomas. ER/PR/bcl-2 negativity will sometimes be helpful to confirm the diagnosis of apocrine carcinoma, because it is more consistent than GCDFP-15/AR positivity.
Adult↗
[Oculomotor muscles involvement revealing dermatomyositis in a patient with rheumatoid arthritis].
INTRODUCTION: Oculomotor muscles (OMM) involvement in dermatomyositis (DM) and in rheumatoid arthritis (RA) is unusual. The DM always leads to OMM inflammation, whereas the RA particularly leads to tenosynovitis of the superior oblique muscle referred to as the Brown syndrome. OBSERVATION: The patient is a 43-year-old woman who gives a 17-year-history of severe seropositive RA with bilateral coxite. She was hospitalized for acute painful proptosis. The clinical examination revealed an orbital erythema and a muscular rhizomelic weakness. The muscular enzymes were increased. The orbital CT revealed in the right side, an enlargement of the superior rectus muscle that was enhanced after intravenous injection, which is compatible with myositis involvement. The muscular biopsy practiced at the level of the calf showed the specific histological signs of the DM. This orbital involvement was resolved with a high dose of corticosteroids. CONCLUSION: Our observation has the specificity of associating RA with DM with an involvement of the superior rectus muscle, which is due to the DM rather than the RA.
Adult↗
Detection of oxidative DNA damage in oesophageal biopsies of patients with reflux symptoms and normal pH monitoring.
BACKGROUND: Gastro-oesophageal reflux has been shown to induce oxidative DNA damage. AIM: To determine whether oxidative DNA damage, detected in oesophageal biopsies by simple immunohistochemical staining, correlates with gastro-oesophageal reflux disease as determined by pH monitoring. METHODS: The study included 47 patients with reflux symptoms who had oesophageal biopsy and 24-h pH monitoring studies performed within 3 months of each other with no variation in treatment in the time between the two procedures. Sections of formalin-fixed and paraffin-embedded oesophageal biopsies were stained for 8-hydroxy-2'-deoxyguanosine using the standard immunoperoxidase method. Positive nuclear immunoreactivity was considered to indicate oxidative DNA damage. RESULTS: Seven (33%) of the 21 cases with normal 24-h pH monitoring results were negative for oxidative DNA damage, compared with only two (8%) of the 26 cases with abnormal 24-h pH results (P=0.058, two-sided Fisher's exact test). Five of the patients with normal 24-h pH results had oesophageal biopsies performed within 24 h of the monitoring procedure and, of these, four (80%) were positive for oxidative DNA damage, including a case in which both biopsy and 24-h pH monitoring were performed on the same day whilst the patient was on proton pump inhibitor therapy. All cases with normal 24-h pH results and positive oxidative DNA damage showed features of reflux on routine morphological evaluation. CONCLUSIONS: Oxidative DNA damage can occur in the absence of acid reflux and despite adequate antisecretory therapy. This may indicate that other agents, such as bile, can induce oxidative DNA damage in an acid-suppressed environment. The significant discordance between oxidative DNA damage and 24-h pH results makes the determination of oxidative DNA damage a poor surrogate marker for 24-h pH monitoring.
8-Hydroxy-2'-Deoxyguanosine↗
Receptor activator of nuclear factor kappaB (RANK) is expressed as a late event during malignant progression in Barrett's metaplasia.
Receptor activator of NF-kappaB (RANK) activation induces several survival signals including nuclear factor kappaB (NF-kappaB) and activation and upregulation of Bcl-xL. The aim of this work was to determine whether RANK is expressed in oesophageal adenocarcinoma (EA) and its precursor, Barrett's metaplasia (BM). Sections of formalin-fixed and paraffin-embedded tissue from 23 oesophagectomy specimens showing EA and variable degrees of dysplasia in BM were immunohistochemically stained for RANK. All 23 carcinomas (100%) showed strong RANK immunoreactivity in most cancer cells. In 8 cases with high-grade dysplasia (HGD), RANK immunoreactivity was weaker and detected in a smaller percentage of cells. RANK was not detected in any area of BM that was negative for dysplasia (ND) (17 cases), or showed low-grade dysplasia (LGD) (9 cases). These results indicate that RANK is expressed as a late event during malignant progression in BM. Studies are needed to determine whether interfering with RANK signalling affects the survival of EA cells.
Adenocarcinoma↗
Breast carcinoma in women over the age of 85: distinct histological pattern and androgen, oestrogen, and progesterone receptor status.
AIMS: The pathogenesis of breast carcinoma in very elderly women is of interest, because oestrogen levels are likely to be extremely low during the development of the disease. In an effort to understand the pathogenesis of breast carcinoma in these women, this study was undertaken to compare the histological patterns and hormone receptor status of breast carcinomas arising in very elderly and younger women. METHODS AND RESULTS: Thirty-seven breast carcinomas from women over the age of 85 years at the time of their operation were examined histologically and compared with those from a large group of premenopausal women. The proportions of mucinous carcinoma and apocrine carcinoma were significantly greater in older women. The expression of steroid hormone receptors was studied immunohistochemically. Androgen receptor-positive carcinomas were significantly more frequent among older women, whereas progesterone receptor-positive carcinomas were significantly less frequent. There was no statistically significant difference in oestrogen receptor-alpha or -beta expression between the tumours from both groups. CONCLUSION: Breast carcinomas in women over the age of 85 years have a different morphological spectrum from carcinomas in younger age groups and may have different pathogenesis mechanisms that may be more dependent on androgen and androgen receptor interaction. Differences from the results of the other studies are discussed.
Adenocarcinoma↗
[Tubercular abscess of the psoas without associated spinal involvement. A case report].
INTRODUCTION: Tuberculous psoas abscess outside of locoregional causes is uncommon and can cause a problem of differential diagnosis. EXEGESIS: We report a case of unilateral tuberculous abscess of the psoas which first clinical and radiological features presented like a retroperitoneal tumor. Exploration laparotomy discovered a bulky abscess of the left psoas muscle. Bacteriologic and histologic evaluation confirmed the tuberculous origin. Radiological study of the spine did not show any signs of spondylodiscitis. Under antituberculosis treatment a crural collection occurred and a surgical drainage was performed. Five years later, there was a recurrence of a crural collection which responded well to antituberculosis treatment. CONCLUSION: Tuberculous psoas abscess is usually secondary to spinal involvement, more uncommonly to digestive, urologic or genital tuberculosis. Primary abscess was rarely described and the pathogenesis remains unclear. Psoas contamination is supposed to be hematogenous or lymphatic in origin. Ultrasonography and computed tomography (CT) transformed the diagnosis and the therapeutic approach by percutaneous puncture and drainage.
Adult↗
Incidence and survival trends of esophageal carcinoma in the United States: racial and gender differences by histological type.
BACKGROUND: The incidence of esophageal adenocarcinoma in White males has been reported to be increasing. The aims of this study were to determine: 1) the incidence trends of esophageal carcinoma in the United States with an emphasis on histologic type, sex, and ethnicity, 2) whether the reported increase in stage IV tumors can be confirmed, and 3) survival trends and factors affecting survival. METHODS: Data from the SEER program of the National Cancer Institute with submission dates 1973-98 were used. Data on Hispanics were available for analysis only for the years 1992-98. Statistical analysis was performed utilizing SEER*Stat and SAS statistical software packages. RESULTS: The incidence of adenocarcinoma in White males is still rising (7.8%/year, P < 0.0001); however, the same trend was observed for White females (6.48%/year; P < 0.0001). Hispanic males (3.91 %/year; P < 0.02), and Hispanic females (9.4%/ year; P < 0.04). The incidence of squamous cell carcinoma has been steadily declining in White males and females and in Black females since 1973, with the incidence showing a dramatic and significant decline in Black males beginning in 1992 (8.53%/year; P = 0.0009). Stage 4 carcinoma is declining in incidence. Survival of patients with esophageal carcinomas has been improving. In a Cox multivariate model, independent prognostic factors in esophageal carcinoma included tumor stage, tumor type, gender, race, age at diagnosis, and year of diagnosis. CONCLUSIONS: 1) The incidence of adenocarcinoma continues to rise in White males and females, but also in Hispanics, while squamous cell carcinoma is declining; 2) the incidence of stage 4 carcinomas has been declining, and 3) survival has been steadily improving, independently of all other risk factors.
Adenocarcinoma↗
Functional expression of receptor activator of nuclear factor kappaB in Hodgkin disease cell lines.
The malignant Hodgkin and Reed-Sternberg (H/RS) cells of Hodgkin disease (HD) express several members of the tumor necrosis factor (TNF) receptor family, including CD30 and CD40, and secrete several cytokines and chemokines. However, little is known about what regulates cytokine and chemokine secretion in H/RS cells. Although H/RS cells are predominantly of B-cell origin, they frequently share phenotypic and functional features with dendritic cells (DCs). Previous studies reported that receptor activator of nuclear factor kappaB (NF-kappaB) (RANK), a member of the TNF receptor family, is expressed on DCs, and that RANK ligand (RANKL) enhances DC survival and induces them to secrete cytokines. This study reports that, similar to DCs, cultured H/RS cells expressed RANK. However, unlike DCs, H/RS cells also expressed RANKL. Soluble RANKL activated NF-kappaB and induced messenger RNA expression of interferon-gamma, interleukin-8 (IL-8), IL-13, IL-9, IL-15, and RANTES, in addition to the receptors for IL-9, IL-13, IL-15, and CCR4. RANKL increased IL-8 and IL-13 levels in the supernatants of H/RS cell lines, an effect that was blocked by soluble RANK. Furthermore, soluble RANK decreased the basal level of IL-8 in one cell line, suggesting that IL-8 was induced by an autocrine RANKL/RANK loop. RANKL had no effect on H/RS cell survival in culture, and it did not modulate the expression of bcl-2, bcl-xL, bax, or inhibitors of apoptosis proteins. These data provide evidence of further functional similarities between DCs and H/RS cells. The coexpression of RANK and RANKL in H/RS cells suggests that they may regulate cytokine and chemokine secretion in H/RS cells by an autocrine mechanism.
Antigens, Surface↗
A method for measuring passive elastance during proportional assist ventilation.
There are currently no reliable, noninvasive ways to monitor respiratory elastance (E) during assisted ventilation. We describe a method that is suited for proportional assist ventilation (PAV). In this mode, the end of the ventilator's inflation phase occurs during the declining phase of inspiratory effort (Pmus). If the opening of the exhalation valve is delayed, airway pressure (Paw) should initially rise as Pmus continues its decline. When Pmus declines to zero, a Paw plateau should appear. Paw at this point should reflect passive recoil at the prevailing volume. A cohort of 74 ventilator-dependent patients, ventilated in the PAV mode, were studied. Brief end-inspiratory occlusions were applied at random intervals. The magnitude of early change in Paw during the occlusion was inversely related to level of assist (r = 0.7, p < 0.00001). At high assist (> 75%), Paw was nearly flat or declined slightly, indicating minimal residual Pmus at the onset of occlusion. At lower assist levels, Paw increased exponentially in most patients with an average time constant of 0.21 +/- 0.06 s. Extraneous events that may corrupt the measurement (e.g., behavioral responses) were extremely rare (< 0.5%) in the first 0.25 s. From these findings, we concluded that Paw measured 0.25 s from occlusion onset (P0.25) includes little inspiratory Pmus and is free of extraneous events. E, estimated from P0.25 during PAV (EPAV), agreed well (r = 0.92) with passive E measured during controlled ventilation (ECMV); the average difference (EPAV - ECMV) was (+/- SD) -0.3 +/- 4.9 cm H2O x L(-1), corresponding to 0.9 +/- 16.4% of average E. We conclude that Paw measured at 0.25 s from the onset of end-inspiratory occlusion in the PAV mode provides a reliable estimate of passive elastic recoil.
Adult↗
IPCS conceptual framework for evaluating a mode of action for chemical carcinogenesis.
The International Programme on Chemical Safety (IPCS) is leading an activity to harmonize approaches to cancer risk assessment as a part of its larger project on the Harmonization of Approaches to the Assessment of Risk from Exposure to Chemicals. Through a series of workshops and the evaluation of case studies, a number of key components of risk assessments relating to harmonization were identified: transparency, terminology, weight of evidence, flexibility, and accessibility/communication. A major impediment to harmonization identified in the consideration of weight of evidence was the evaluation of mode of action. To address this need, a conceptual framework was developed, based on the general principles involved in considering the chemical induction of a specific tumor in animals. This is based partly on the Bradford Hill criteria for causality as modified by Faustman et al. (1997) for developmental toxicity. The framework is described in this paper followed by a worked example. It is recognized that the framework addresses only one stage in the overall characterization of hazard to humans of chemical carcinogens. Another important but separate step is the assessment of relevance to humans. This is a priority area for future work in this project.
Animals↗
Photodynamic therapy and genetic abnormalities.
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Barrett Esophagus↗
Estrogen receptor beta expression in invasive breast cancer.
The aim of this work was to determine the extent of estrogen receptor beta (ER-beta) expression in invasive breast cancer (BrCA) and whether ER-beta expression is correlated with response to adjuvant hormonal therapy with tamoxifen (AHTT). Immunohistochemical staining (IHC) for estrogen receptor alpha (ER-alpha) and ER-beta was performed on sections of formalin-fixed and paraffin-embedded tissue from 47 unselected invasive breast carcinomas (BrCA). IHC for ER-beta was also performed on sections of BrCA from 118 women who were treated with mastectomy and AHTT. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. Of the 47 unselected BrCA, 17 (36%) were negative for ER-alpha and of these, 8 (47% of ER-alpha negative cases and 17% of all 47 patients) were ER-beta positive. Five of the 8 ER-alpha negative and ER-beta positive cases were positive for ER biochemically. There was no correlation between ER-beta positivity and overall survival in the unselected group. By contrast, in the group of women treated with AHTT, expression of ER-beta in more than 10% of cancer cells was associated with better survival (P = .0077), even in women with node-negative BrCA (P = .0069). In conclusion, our results show that a significant number of women with BrCA are positive for ER-beta only, and may be determined to be ER-negative when currently available IHC is used. ER-beta status is a significant predictor of response to AHTT in women with BrCA. Larger studies with multivariate analysis are needed to confirm these findings.
Blotting, Western↗
Estrogen receptor beta is expressed in human colorectal adenocarcinoma.
Estrogen receptor beta (ER-beta) has recently been detected in a human colon cancer cell line. The aim of this work was to determine whether ER-beta is expressed in human colorectal carcinoma (CRC) tissue and the extent of this expression. ER-beta expression in CRC was investigated by immunohistochemical staining of sections of formalin-fixed, paraffin-embedded tissue from 55 CRC. The percent of positive cells was recorded. ER-beta immunoreactivity was always present in normal epithelium and adenomas in the same sections of some CRC and was always nuclear. In CRC, nuclear ER-beta immunoreactivity was detected in >10% of the cancer cells in 67% of the cases and was almost always associated with cytoplasmic immunoreactivity. There were no statistically significant differences between the ER-beta-positive and -negative groups in regard to depth of invasion, nodal metastases, or survival, regardless of the cut-off value used. We conclude that (1) a significant number of CRCs are positive for ER-beta. (2) estrogen may play an important role in the proliferation of normal colonic epithelium, and (3) there is differential localization of ER-beta immunoreactivity between normal colon, adenomas, and CRCs. Whether different ER-beta isoforms are differentially expressed in CRCs, and whether human CRCs respond to treatment with antiestrogens, is the subject of studies currently in progress.
Adenocarcinoma↗
Waterborne health risks and the WHO perspective.
The benefits of improved water and sanitation include both health and non-health effects. The direct health benefits are related to two contrasting roles of water: that of disease vector when it carries pathogens; and that of health mediator through its use in personal and domestic hygiene. Indirect effects related to health include for example improved quality of life and decreased expenditure on medical expenses. Non-health effects include time savings for productive activity or education. The fact that the health impact of inadequate water supply services, especially in the developing world, has never been established is recognised (Troare, 1992) and recent work highlights unrecognised health burdens elsewhere--both from apparently good quality supplies (Payment et al., 1991; Payment et al., 1997); and from outbreaks of disease (Ford and Colwell, 1996). This paper looks at the WHO perspective on waterborne health risks and is divided into three main sections: our knowledge of the existing situation; recognised and emerging priorities arising from the changing context; and the availability of approaches and tools to meet the recognised and emerging priorities.
Developing Countries↗
A method for noninvasive determination of inspiratory resistance during proportional assist ventilation.
Currently available noninvasive methods for measuring inspiratory resistance (RI) are difficult to implement or interpret during assisted mechanical ventilation on account of the confounding effect of respiratory efforts (Pmus). We propose a simple method consisting of brief reductions in airway pressure (Paw) in the early part of the inflation phase (pulse). Paw, flow (V), and volume (V) are measured at the beginning of the pulse (T (0)), at the trough of the pulse (TI) and at a point 0.1 s before T(0) (T(-1)). Equations of motion of the form [Pmus + Paw = V. K(1) + V (2). K(2) +V. E] are generated for the data at the three time points (E = elastance, K(1) and K(2) are Rohrer's constants). These three equations can be solved for K(1) and K(2) if it is arranged that the pulse has appropriate configuration and timing, and if it is assumed that DeltaPmus/Deltat is constant over the brief pulse period. The method was tested in 67 patients ventilated with proportional assist ventilation (PAV). The results were compared with those obtained using the interrupter technique during a period of controlled mechanical ventilation (CMV). RI, expressed at a standard flow of 1 L. s(-)(1), was slightly higher during PAV (16.4 +/- 4.9 versus 15.5 +/- 4.5 cm H(2)O. L(-1). s, p < 0.001). The average difference was 0.9 +/- 2.0 cm H(2)O. L(-1). s, corresponding to 5.4 +/- 12.6% of the average of RCMV and RPAV. The correlation coefficient was 0.92 (p = 8E-28) with a slope (1.01) and intercept (0.8) not significantly different from 1.0 and 0, respectively. We conclude that brief negative pulses applied early during the inflation phase can be used to provide reliable estimates of inspiratory resistance during PAV.
Airway Resistance↗
Chemical control stability in patients with obstructive sleep apnea.
The role of chemical control instability in the pathogenesis of obstructive sleep apnea (OSA) is not clear. We studied 32 patients with OSA during sleep while their upper airway was stabilized with continuous positive airway pressure. Twelve patients had repetitive OSA whenever they were asleep, regardless of body position or sleep stage, and were classified as having severe OSA (apnea-hypopnea index [AHI] = 88 +/- 19). The remaining 20 patients had sporadic OSA or repetitive OSA for only part of the time (mild/moderate OSA; AHI = 27 +/- 16). Susceptibility to periodic breathing (PB) was assessed by gradually increasing controller gain, using proportional assist ventilation. The increase in loop gain (LG) at each assist level was quantified from the ratio of assisted tidal volume (VT) to the VT obtained during single-breath reloading tests (VT amplification factor [VTAF]). Nine of 12 patients with severe OSA developed PB, with recurrent central apneas, whereas only six of 20 patients in the mild/moderate group developed PB (p < 0.02). This difference was observed despite the subjection of the mild/moderate group to greater amplification of LG; the highest values of VTAF in the mild/moderate and severe groups were 2.7 +/- 1.0 and 1.9 +/- 0.7, respectively (p < 0.01). We conclude that the chemical control system is more unstable in patients with severe OSA than in patients with milder OSA. We speculate that this may contribute to the severity of OSA, at least in some patients.
Chemoreceptor Cells↗
Apnea following mechanical ventilation may not be caused by neuromechanical influences.
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Apnea↗