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Disease Progression (disease + progression)
Kinds of Disease Progression Terms modified by Disease Progression Selected AbstractsDisease Progression in Hemodynamically Stable Patients Presenting to the Emergency Department With SepsisACADEMIC EMERGENCY MEDICINE, Issue 4 2010Seth W. Glickman MD Abstract Background:, Aggressive diagnosis and treatment of patients presenting to the emergency department (ED) with septic shock has been shown to reduce mortality. To enhance the ability to intervene in patients with lesser illness severity, a better understanding of the natural history of the early progression from simple infection to more severe illness is needed. Objectives:, The objectives were to 1) describe the clinical presentation of ED sepsis, including types of infection and causative microorganisms, and 2) determine the incidence, patient characteristics, and mortality associated with early progression to septic shock among ED patients with infection. Methods:, This was a multicenter study of adult ED patients with sepsis but no evidence of shock. Multivariable logistic regression was used to identify patient factors for early progression to shock and its association with 30-day mortality. Results:, Of 472 patients not in shock at ED presentation (systolic blood pressure > 90 mm Hg and lactate < 4 mmol/L), 84 (17.8%) progressed to shock within 72 hours. Independent factors associated with early progression to shock included older age, female sex, hyperthermia, anemia, comorbid lung disease, and vascular access device infection. Early progression to shock (vs. no progression) was associated with higher 30-day mortality (13.1% vs. 3.1%, odds ratio [OR] = 4.72, 95% confidence interval [CI] = 2.01 to 11.1; p , 0.001). Among 379 patients with uncomplicated sepsis (i.e., no evidence of shock or any end-organ dysfunction), 86 (22.7%) progressed to severe sepsis or shock within 72 hours of hospital admission. Conclusions:, A significant portion of ED patients with less severe sepsis progress to severe sepsis or shock within 72 hours. Additional diagnostic approaches are needed to risk stratify and more effectively treat ED patients with sepsis. ACADEMIC EMERGENCY MEDICINE 2010; 17:383,390 © 2010 by the Society for Academic Emergency Medicine [source] Pathophysiology and Disease Progression of Atrial Fibrillation: Importance of Achieving and Maintaining Sinus RhythmJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2008F.A.C.C., MARC COHEN M.D. Atrial fibrillation (AF) is a progressive disease in which arrhythmia-induced remodeling facilitates evolution from paroxysmal AF to persistent and permanent AF. Changes in electrical, structural, and contractile properties of cardiac tissue that are thought to underlie AF maintenance and progression are reviewed. Also examined is the negative impact of AF on clinical outcomes, as well as the potential benefits of restoration and maintenance of sinus rhythm. Because of the limited efficacy and adverse effects of current antiarrhythmics, new antiarrhythmic drugs need to be developed that provide safer and more effective rhythm control in AF. [source] ACE Inhibitors and Protection Against Kidney Disease Progression in Patients With Type 2 Diabetes: What's the Evidence?JOURNAL OF CLINICAL HYPERTENSION, Issue 6 2002George L. Bakris MD Although angiotensin-converting enzyme inhibitors are frequently used as antihypertensive agents to lower blood pressure and slow progression of nephropathy in patients with type 2 diabetes, evidence of their efficacy has been drawn primarily from small trials with surrogate end points. No adequately powered, long-term trials have tested their effects to reduce the incidence of hard end points, such as progression to end-stage renal disease or even doubling of serum creatinine in the population of patients with nephropathy from type 2 diabetes. While the results of angiotensin-converting enzyme inhibitor trials from nondiabetic causes and even type 1 diabetes may be extrapolated to the patient with nephropathy associated with type 2 diabetes, the hard evidence is not available. This review critically evaluates the limited evidence in support of angiotensin-converting enzyme inhibitors as renal-protective agents in people with type 2 diabetes. [source] Vitamin A and HIV Infection: Disease Progression, Mortality, and TransmissionNUTRITION REVIEWS, Issue 10 2000Chinaro M. Kennedy Dr.P.H. Among HIV-infected individuals, many nutritional factors that influence disease progress, mortality, and transmission are not well understood. Of particular interest is the role of vitamin A. The benefits of vitamin A have been recognized since ancient times by Egyptian physicians who successfully treated night blindness with vitamin A. Contemporary scientists have since recognized the importance of vitamin A and have provided evidence that it may help in repairing damaged mucosal surfaces; what remains unclear, however, is its role during HIV infection. In this review, we examine the evidence provided in both observational studies and randomized controlled trials that assessed the effect of vitamin A during HIV infection. [source] Tissue Factor Expression and Serum Level in Patients with Melanoma does not Correlate with Disease ProgressionPIGMENT CELL & MELANOMA RESEARCH, Issue 3 2001Toshiro Kageshita Not only does tissue factor (TF) play a crucial role in hemostasis and thrombosis, but it is also involved in tumor progression and metastatic potency in some malignant tumors. We evaluated the clinical relevance of TF expression in melanocytic tumors and TF serum level in patients with malignant melanoma. TF expression in benign and malignant melanocytic lesions was examined by immunoperoxidase staining in 20 nevi, 41 primary, and 24 metastatic melanoma lesions. TF was detected in 94, 95, and 100% of these lesions, respectively. The staining pattern was membranous and cytoplasmic both in nevi and melanoma cells. This finding was confirmed by western blot analysis using cultured human melanocytes, nevi cells, and melanoma cell lines. TF was also expressed on blood vessels in benign and malignant melanocytic lesions. Expression of TF in primary melanoma lesions was not associated with any clinicopathological variables. In addition, the serum level of TF was elevated in 14% of patients with melanoma; however, it was not correlated with disease progression. These results suggest that TF was ubiquitously expressed in melanocytic cells and its expression was not correlated with disease progression and/or metastatic potency of melanoma cells. [source] Protein Expression of the Tumor Suppressors p16INK4A and p53 and Disease Progression in Recurrent Respiratory PapillomatosisTHE LARYNGOSCOPE, Issue 2 2007Truc T. Pham MD Abstract Background: Recurrent respiratory papillomatosis (RRP) is a benign condition that rarely metastasizes as invasive squamous cell carcinoma. Although this disease is associated with human papillomavirus, the role of this virus in tumorigenesis is unclear. Objectives: The aim of this study is to assess the involvement of the tumor suppressors P16INK4A and p53 in RRP tumor progression. Design: Immunohistochemistry of p16INK4A and p53 was performed on biopsies of recurrent squamous papillomas and invasive lesions in nine patients. Results: Twenty biopsies were graded as papillomas (RP), three as papillomas with high-grade dysplasia/carcinoma in situ (HGD/CIS), and two as invasive squamous cell carcinoma (SCCA). Forty-five percent of RP and 60% of HGD/CIS/SCCA expressed p16INK4A. Fifty percent of RP and 100% of HGD/CIS/SCCA expressed p53. The difference in the frequency of p53-positive staining between HGD/CIS and SCCA (100% of tissues examined) and RP (50% of tissues examined) approached statistical significance. Neither p16INK4A nor p53 was predictive of invasive transformation. Conclusions: Expression of p16INK4A, which is a surrogate for the tumor suppressor retinoblastoma (Rb), did not immediately lead to invasive disease. There is no correlation between disease severity of RRP and level of p16INK4A. [source] Structured treatment interruption in patients with alveolar echinococcosisHEPATOLOGY, Issue 2 2004Stefan Reuter In human alveolar echinococcosis (AE), benzimidazoles are given throughout life because they are only parasitostatic. It has been a longstanding goal to limit treatment, and recent reports suggest that, in selected cases, benzimidazoles may be parasitocidal. Previously, we showed that positron ,emission tomography (PET) using [18F]fluoro-deoxyglucose discriminates active from inactive lesions in AE. We have now performed a 3-year prospective study in 23 patients and conducted a structured treatment interruption in those without signs of PET activity. Disease progression was further assessed by ultrasound, computerized tomography, laboratory parameters, and clinical examination. We found PET-negative lesions in 15 of 23 patients and benzimidazoles were discontinued in these patients. After 18 months, patients were reevaluated, and, of the 15 initially PET-negative patients, 8 showed either new activity on PET (n = 6) or signs of clinical progression (n = 2). Reinitiation of benzimidazoles halted parasite growth again. No further progression was detected after 36 months. PET had a sensitivity of 91% for the detection of active lesions. In conclusion, despite successful suppression of metabolic activity, in most cases benzimidazoles do not kill the parasite. PET is a reliable tool for assessing metabolic activity and for timely detection of relapses. Neither duration of treatment, kind of treatment, lesion size, calcifications, or regressive changes reliably indicate parasite death. We discourage the discontinuation of benzimidazoles in inoperable AE even after many years of treatment. However, patients with a poor compliance of benzimidazole intake or patients suffering from side effects to benzimidazoles might be assessed for PET negativity. If permanent discontinuation of benzimidazoles is attempted, the course of disease should be followed by PET. (HEPATOLOGY 2004;39:509,517.) [source] Surgical outcomes of partial nephrectomy for renal cell carcinoma: A joint study by the Japanese Society of Renal CancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2007Yutaka Senga Objective: A joint study was undertaken by the Japanese Society of Renal Cancer to investigate the present status of partial nephrectomy in Japan and to speculate about what may be the indications for partial nephrectomy in patients with renal cell carcinoma. Methods: Data were tabulated for 469 patients from participating medical institutions and various clinical factors were investigated with regard to disease progression (local recurrence and distant metastasis). Results: Disease progression was observed in 21 patients (4.5%). No significant relation to disease progression was observed for sex, laterality, tumor histology, grade and tumor size. Although patients with solitary tumors displayed excellent prognosis irrespective of tumor diameter, patients with multiple tumors displayed a high likelihood of disease progression. Patients older than 77 years old and patients with imperative indication were found to have a poorer prognosis. Conclusion: In patients with solitary tumors, partial nephrectomy can be actively performed, even if the patient displays elective indications and the tumor is >4 cm in diameter. In patients displaying multiple tumors with imperative indications, the decision whether to perform partial nephrectomy should be made by the patients and their physicians after considering the impact on curability and the quality of life. [source] Adjunctive benefits of systemic amoxicillin and metronidazole in non-surgical treatment of generalized aggressive periodontitis: a randomized placebo-controlled clinical trialJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2005Adrian Guerrero Abstract Background: The objective of this study was to assess the adjunctive clinical effect of the administration of systemic amoxicillin and metronidazole in the non-surgical treatment of generalized aggressive periodontitis (GAP). Methods: Forty-one systemically healthy subjects with GAP were included in this 6-month double-blind, placebo-controlled, randomized clinical trial. Patients received a course of full-mouth non-surgical periodontal treatment delivered over a 24 h period using machine-driven and hand instruments. Test subjects received an adjunctive course of systemic antibiotic consisting of 500 mg amoxicillin and 500 mg metronidazole three times a day for 7 days. Clinical parameters were collected at baseline, and at 2 and 6 months post-treatment. Results: In both the test and the placebo groups, all clinical parameters improved at 2 and 6 months. In deep pockets (7 mm), the test treatment resulted in an additional 1.4 mm (95% confidence interval 0.8, 2.0 mm) in full-mouth probing pocket depth (PPD) reduction and 1 mm (0.7, 1.3 mm) of life cumulative attachment loss (LCAL) gain at 6 months. In moderate pockets (4,6 mm), the adjunctive benefit was smaller in magnitude: PPD reduction was 0.4 mm (0.1, 0.7 mm) and LCAL gain was 0.5 mm (0.2, 0.8 mm). In addition, the 6-month data showed LCAL gains 2 mm at 25% of sites in test patients compared with 16% in placebo (p=0.028). Similarly, PPD reductions of 2 mm or more were observed in 30% of sites in test and 21% of sites in placebo patients. Seventy-four percent of pockets with PPD 5 mm at baseline were 4 mm or shallower at 6 months in the test group. This compared with 54% in the placebo group (p=0.008). Disease progression at 6 months was observed at 1.5% of test and 3.3% of sites in test and placebo, respectively (p=0.072). Conclusions: These data indicate that a 7-day adjunctive course of systemic metronidazole and amoxicillin significantly improved the short-term clinical outcomes of full-mouth non-surgical periodontal debridement in subjects with GAP. [source] Postnatal glutamate-induced central nervous system lesions alter periodontal disease susceptibility in adult Wistar ratsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2001Torbjørn Breivik Abstract Background: Inability to mount a suitable brain-neuroendocrine response to bacterial or other antigenic challenges has been found to play an important rôle in infectious and inflammatory disease susceptibility and progression, including periodontal disease. Objective: The present study was designed to determine the effects of glutamate administration to new-born Wistar rats on the development and progression of naturally occurring and ligature-induced periodontal disease in the rats as adults. Postnatal glutamate administration is known to permanently damage neurones in the hypothalamic arcuate nucleus. Method: New-born rats were treated 1× daily subcutaniously with 2 mg/g of monosodium-L-glutamate (MSG) for 5 days from day 3 to 6. Control animals were injected with similar amounts of saline. Experimental ligature-induced periodontal disease was induced in the rats at the age of 12 weeks at maxillary right 2nd molar teeth. The contralateral maxillary left 2nd molars served as control teeth, and for assessment of naturally occurring periodontal disease. Disease progression was evaluated histometrically. Results: The results revealed that the glutamate-lesioned rats developed significantly more periodontal tissue destruction compared to sham-lesioned control rats in both the ligated and non-ligated teeth. Conclusions: This study supports our resent findings indicating that inappropriate brain-neuroendocrine-immune regulation may play a rôle in periodontal disease susceptibility and progression. Zusammenfassung Hintergrund: Es hatte gezeigt werden können, dass die Unfähigkeit des Gehirns auf einen bakteriellen oder antigenen Reiz mit einer angemessenen neuroendokrinen Antwort zu reagieren, eine wichtige Rolle für die Empfänglichkeit für infektiöse und entzündliche Erkrankungen einschliesslich Parodontitis spielt. Die Gabe von Glutamat nach der Geburt führt zu irreversiblen Schäden der Neurone des Nucleus arcuatus des Hypothalamus. Zielzetzung: Untersuchung der Auswirkungen von Glutamatgaben bei neugeborenen Wistar-Ratten auf die Entstehung und das Fortschreiten natürlich vorkommender und ligaturinduzierter Parodontitis im Erwachsenenalter. Material und Methoden: Bei 24 neugeborenen Wistar-Ratten wurden einmal täglich 2 mg/g L-Mononatriumglutamat und bei 20 Kontrolltieren statt dessen Kochsaltzlösung vom 4. Lebenstag an 4 Tage lang subkutan injiziert. Am rechten zweiten Oberkiefermolaren wurden bei den 12 Wochen alten Ratten eine experimentelle ligaturinduzierte Parodontitis ausgelöst. Der kontralaterale 2. Molar des Oberkiefers diente als Kontrolle und um natürlich vorkommende Parodontitis zu untersuchen. Das Fortschreiten der parodontalen Zerstörung wurde histometrisch erfasst. Ergebnisse: Die Ergebnisse zeigten, dass die Ratten mit den glutamatinduzierten Läsionen statistisch signifikant stärkere parodontale Zerstörungen sowohl an den Zähnen mit wie auch an denen ohne Ligaturen im Vergleich zur Kontrollgruppe aufwiesen. Schlussfolgerungen: Eine unangemessene neuroendokrinoimmunologische Regulation des Gehirns scheint eine Rolle bei der Empfänglichkeit für und das Fortschreiten von Parodontitis zu haben. Résumé Origine: L'incapacitéàétablir une réponse neuroendocrinienne cervicale efficace pour des défis bactériens ou antigèniques joue un rôle important dans la susceptibilité et la progression des maladies infectieuses et inflammatoires, dont les parodontites. But: Cette étude a été imaginée pour déterminer les effets de l'administration de glutamate à des rats Wistar nouveau-nés sur le développement et la progression de maladies parodontales naturelles et induites par des ligatures chez le rat adulte. On sait que l'administration de glutamate en postnatal endommage de façon permanente les neurones du noyau d'arc hypothalamique. Méthodes: Les rats nouveaus-nés furent traités une fois par jour par administration sous cutanée de 2 mg/g de monosodium-L-glutamate (MSG) pendant 5 jours. Les animaux contrôles recevaient une dose similaire de sérum physiologique. La parodontite expérimentale par ligature était réalisée à l'âge de 12 semaines, sur la deuxième molaire supérieure droite. La dent controlatérale servait de contrôle et à la mise en évidence de maladie parodontale naturelle. La progression de la maladie fut évaluée par histométrie. Résultats: Les résultats montrent que les rats atteints de lésions dues au glutamate développent plus de destructions parodontales (par ligatures ou sans ligatures) par rapport aux rats contrôles atteints de lésions simulées. Conclusion: Cette étude supporte nos récentes découvertes qui indiquent qu'une régulation immunitaire neuroendocrinienne cervicale inappropriée peut jouer un rôle dans la susceptibilité et la progression des maladies parodontales. [source] Disease progression of human SOD1 (G93A) transgenic ALS model ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2006Arifumi Matsumoto Abstract The recent development of a rat model of amyotrophic lateral sclerosis (ALS) in which the rats harbor a mutated human SOD1 (G93A) gene has greatly expanded the range of potential experiments, because the rats' large size permits biochemical analyses and therapeutic trials, such as the intrathecal injection of new drugs and stem cell transplantation. The precise nature of this disease model remains unclear. We described three disease phenotypes: the forelimb-, hindlimb-, and general-types. We also established a simple, non-invasive, and objective evaluation system using the body weight, inclined plane test, cage activity, automated motion analysis system (SCANET), and righting reflex. Moreover, we created a novel scale, the Motor score, which can be used with any phenotype and does not require special apparatuses. With these methods, we uniformly and quantitatively assessed the onset, progression, and disease duration, and clearly presented the variable clinical course of this model; disease progression after the onset was more aggressive in the forelimb-type than in the hindlimb-type. More importantly, the disease stages defined by our evaluation system correlated well with the loss of spinal motor neurons. In particular, the onset of muscle weakness coincided with the loss of approximately 50% of spinal motor neurons. This study should provide a valuable tool for future experiments to test potential ALS therapies. © 2005 Wiley-Liss, Inc. [source] Disease progression in amyotrophic lateral sclerosis: Predictors of survivalMUSCLE AND NERVE, Issue 5 2002T. Magnus MD Abstract Predicting the rate of disease progression has become important as trials of new medical treatments for amyotrophic lateral sclerosis (ALS) are planned. Bulbar onset, early impairment of forced vital capacity, and older age have all been associated with shorter survival. We performed a retrospective study to compare survival factors with disease progression in a German ALS population. We analyzed disease progression in 155 patients at intervals of 4 months over a period of 3 years. To evaluate disease progression, the ALS functional rating scale (ALS-FRS), forced vital capacity (FVC%), and a Medical Research Council (MRC) compound score based on a nine-step modified MRC scale were used. We compared age (<55 years vs. ,55 years), different sites of disease onset (bulbar vs. limb), and gender to the rate of disease progression and performed survival analyses. No overall significant difference could be detected when analyzing these subgroups with regard to disease progression. By contrast, significantly longer survival was observed in the younger age group (56 months vs. 38 months, P < 0.0001) and in patients with limb-onset disease (51 months vs. 37 months, P = 0.0002). Using Cox analyses values we found that the declines of ALS-FRS, FVC%, and MRC compound score were predictive of survival (P < 0.0001, P = 0.002, and P = 0.003, respectively). Future studies are needed to clarify whether nonspecific factors including muscle atrophy, dysphagia, and coexisting diseases influence prediction of survival in ALS patients. A more precise set of predictors may help to better stratify patient subgroups for future treatment trials. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25:000,000, 2002 [source] Long-term results of single-agent thalidomide as initial therapy for asymptomatic (smoldering or indolent) myeloma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2010Kristen Detweiler-Short We report the long-term follow-up results of a phase II trial of thalidomide for early-stage multiple myeloma (MM). Patients were eligible if they had smoldering multiple myeloma (SMM) or indolent MM without the need for immediate therapy. Thalidomide was initiated at a dose of 200 mg/day and adjusted as tolerated. Disease progression was defined using modified American Society of Hematology/Food and Drug Administration consensus panel criteria for SMM. Thirty-one patients were enrolled; 29 (19 SMM and 10 indolent MM) were eligible. The median age was 61 years. Median follow-up of living patients was 10.2 years (range, 7.5-11.0 years). Ten patients (34%) had a partial response (PR) and nine had minimal response (MR) for an MR plus PR rate of 66%. The median time to progression (TTP) to symptomatic myeloma was 35 months. Median TTP was 61 months in those achieving PR, 39 months with MR, and 9 months among those failing to achieve either MR or PR, P = 0.005. Median overall survival from diagnosis was 86 months; median survival from onset of symptomatic myeloma was 49 months. Grade 3-4 nonhematologic adverse events were noted in 55% of patients. Randomized trials are needed to determine the role of early therapy in SMM. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Formatted anti,tumor necrosis factor , VHH proteins derived from camelids show superior potency and targeting to inflamed joints in a murine model of collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 6 2006Ken Coppieters Objective The advent of tumor necrosis factor (TNF),blocking drugs has provided rheumatologists with an effective, but highly expensive, treatment for the management of established rheumatoid arthritis (RA). Our aim was to explore preclinically the application of camelid anti-TNF VHH proteins, which are single-domain antigen binding (VHH) proteins homologous to human immunoglobulin VH domains, as TNF antagonists in a mouse model of RA. Methods Llamas were immunized with human and mouse TNF, and antagonistic anti-TNF VHH proteins were isolated and cloned for bacterial production. The resulting anti-TNF VHH proteins were recombinantly linked to yield bivalent mouse and human TNF-specific molecules. To increase the serum half-life and targeting properties, an anti,serum albumin anti-TNF VHH domain was incorporated into the bivalent molecules. The TNF-neutralizing potential was analyzed in vitro. Mouse TNF-specific molecules were tested in a therapeutic protocol in murine collagen-induced arthritis (CIA). Disease progression was evaluated by clinical scoring and histologic evaluation. Targeting properties were evaluated by 99mTc labeling and gamma camera imaging. Results The bivalent molecules were up to 500 times more potent than the monovalent molecules. The antagonistic potency of the anti-human TNF VHH proteins exceeded even that of the anti-TNF antibodies infliximab and adalimumab that are used clinically in RA. Incorporation of binding affinity for albumin into the anti-TNF VHH protein significantly prolonged its serum half-life and promoted its targeting to inflamed joints in the murine CIA model of RA. This might explain the excellent therapeutic efficacy observed in vivo. Conclusion These data suggest that because of the flexibility of their format, camelid anti-TNF VHH proteins can be converted into potent therapeutic agents that can be produced and purified cost-effectively. [source] Sequential chemoradiotherapy in advanced laryngeal cancer: An institutional experienceASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2 2010Mohammad Hasan LARIZADEH Abstract Aim: The objective of this study was to determine the efficacy of sequential chemoradiation for larynx preservation. Methods: Between October 2002 and December 2007, 76 patients with T3, T4 and N+ laryngeal cancer who had refused a laryngectomy or had unresectable disease (medically or surgically) enrolled in this study. The chemotherapy consisted of three cycles of docetaxel (75 mg/m2 on day 1), cisplatin (75 mg/m2 on day 1) and 5-flurouracil (5-FU) (750 mg/m2 by infusion on days 1,3). All patients were assigned to receive radiotherapy (70 Gy to primary site). The Kaplan,Meier method was used to obtain survival outcomes. Results: The median follow up was 36 months. A chemotherapy clinical response (complete and partial) was observed in 51 patients (67.1%). The 2-year laryngeal preservation rate was 75%. Actuarial progression-free survival rates of 71% and 67% were observed at 2 and 3 years, respectively. Actuarial overall survival rates were 83% and 71% at 2 and 3 years, respectively. Disease progression was seen in 26 patients (34.2%). Grade 3 and 4 neutropenia occurred in 39 (51.3%) patients. Conclusion: Sequential chemotherapy with docetaxel, cisplatin and 5-flurouracil followed by radiation may be an alternative to a laryngectomy in patients with advanced laryngeal cancer. [source] Head and neck squamous cell carcinoma in 13 patients with Fanconi anemia after hematopoietic stem cell transplantationCANCER, Issue 12 2008Caroline Masserot MD Abstract BACKGROUND. Fanconi anemia (FA) is a chromosomal instability disorder with a very high risk of developing head and neck squamous cell carcinoma (HNSCC), most notably after hematopoietic stem cell transplantation (HSCT). METHODS. In the current study, the authors reported 13 cases of HNSCC in FA patients who underwent HSCT at the Saint Louis Hospital between 1976 and 2007. RESULTS. The median age of the patients at time of HSCT was 9.7 years. All patients received irradiation-based conditioning before HSCT and all developed extensive chronic graft versus host disease (GVHD). HNSCC was diagnosed at a median interval of 10 years after HSCT, mainly in numerous sites within the oral cavity (11 patients). Lymph node involvement was diagnosed in 4 patients. The TNM classification was: T1 in 6 patients, T2 in 2 patients, T3 in 2 patients, and T4 in 3 patients. Treatment was comprised of surgery in 10 patients, with clear surgical margins reported in 7 (including cervical lymph node dissection in 6 patients). Surgery was performed in addition to other treatments in only 2 patients (radiotherapy or cryotherapy). For the remaining 3 patients, treatment consisted in radiotherapy (2 patients) or chemotherapy (1 patient). Disease progression while receiving therapy was observed in 5 patients and 5 other patients developed disease recurrence between 3.5 and 23.7 months after treatment. Death occurred in 11 patients. At the time of last follow-up, only 2 patients were alive without any disease between 9 and 23 months after diagnosis. CONCLUSIONS. HNSCC developing in FA patients after HSCT is associated with a very poor prognosis. A systematic surveillance of the oral cavity is essential to permit early surgery, which to the authors' knowledge remains the only curative treatment for a minority of patients. It is very important to attempt to prevent this cancer by reducing chronic GVHD and using conditioning without irradiation. Cancer 2008. © 2008 American Cancer Society. [source] Restenosis and Progression of Coronary Disease after Balloon Angioplasty in Patients with Diabetes MellitusCLINICAL CARDIOLOGY, Issue 12 2000Yoseph Rozenman M.D. Abstract Background: Patients with diabetes mellitus (D) (both insulin-requiring D [IRD] and non-IRD) who undergo angioplasty have worse long-term outcome than do non-D patients. Few data are available in the literature that explain these findings. Hypothesis: The study was undertaken to compare restenosis and progression of coronary disease after angioplasty in IRD patients, in non-IRD patients, and in non-D patients. Methods: Diabetic patients who underwent coronary angioplasty were separated into two subgroups: IRD and non-IRD patients. Their angiographic outcome was compared with non-D patients. We examined retrospectively 353 coronary angiograms of patients who were referred for diagnostic angiography > 1 month after successful angioplasty. Quantitative angiography was used to determine the outcome in dilated narrowings (restenosis) and in nondilated narrowings (disease progression). Results: Baseline clinical and angiographic characteristics were similar in all groups. Restenosis rate was higher in IRD (61 %) than in non-IRD (36%) and non-D (35%) patients (p = 0.04). Late luminal loss after angioplasty was two times greater in IRD patients than in the other two groups (p=0.01). Disease progression of nondilated narrowings was significantly more prominent in non-IRD than in non-D patients: Diameter stenoses were similar in the initial angiogram, but narrowings were significantly more severe (p=0.02) in the final angiogram (70 ± 27% and 60 ± 33%, respectively). New narrowings were more common in non-IRD than in non-D patients: there was a 23% increase in the number of narrowings in the follow-up angiogram in non-IRD patients compared with only 12% in non-D patients (p < 0.003). These new narrowings were more common (p=0.01) in angioplasty arteries (57 narrowings on 420 arteries,13.6%) than in nonangioplasty arteries (54 narrowings on 639 arteries,8.5%). Conclusion: Restenosis is more common in IRD patients and explains the high rate of adverse cardiac events within the first year after coronary intervention in these patients (mainly target lesion revascularization). Disease progression (including new narrowings) is the main determinant of patient outcome > 1 year after coronary intervention and is accelerated in non-IRD compared with non-D patients. [source] Association of FcGRIIa with Graves' disease: a potential role for dysregulated autoantibody clearance in disease onset/progressionCLINICAL ENDOCRINOLOGY, Issue 1 2010Kadija Yesmin Summary Objective, Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is involved in the clearance of autoantibodies and a functional single nucleotide polymorphism (SNP), rs1801274, which has been shown to alter autoantibody clearance, has been associated with a number of autoimmune diseases (AIDs) including systemic lupus erythematosus and type 1 diabetes. This study aimed to determine whether FcGRIIa is associated with Graves' disease (GD) in the UK Caucasian population by Tag SNP screening common polymorphisms within the FcGRIIa region. Design, A case control association study investigating nine Tag SNPs within FcGRIIa, which captured the majority of known common variation within this gene region. Patients, A dataset comprising 2504 UK Caucasian GD patients and 2784 geographically matched controls taken from the 1958 British Birth cohort. Measurements, We used the ,2 -test to investigate association between the Tag SNPs and GD. Results, Association between the rs1801274 (P,= 0·003, OR = 1·12 [95% CI = 1·03,1·22] and rs6427598 (P = 0·012, OR = 0·90 [95% CI = 0·83-0·98]) SNPs and GD was observed. No other SNPs showed association with GD. No associations were seen between any of the SNPs investigated and specific GD clinical phenotypes. Conclusions, This study suggests that variation in FcGRIIa predisposes to GD and further supports the role of FcGRIIa as a susceptibility locus for AIDs in general. [source] Comparative Overview of Cardiac Output Measurement Methods: Has Impedance Cardiography Come of Age?CONGESTIVE HEART FAILURE, Issue 2 2000Anthony N. De Maria MD Cardiac output, usually expressed as liters of blood ejected by the left ventricle per minute, is a fundamental measure of the adequacy of myocardial function to meet the perfusion needs of tissue at any time. Decreases in cardiac output over time (when cardiac output is measured under similar conditions) may signal myocardial functional deterioration and the onset or progression of heart failure. Conversely, improvements in cardiac output may indicate a positive response to medical therapy. However, most methods for evaluating cardiac output are technically demanding, require specialized training and specialized environments for measurement, and are costly. Therefore, most measurement techniques are impractical for routine evaluation of disease progression and/or response to treatment in the prevention and/or management of heart failure. This paper provides a comparative overview of commonly employed cardiac output measurement strategies with emphasis on developments in impedance cardiography which suggest that impedance cardiography has the potential to make routine assessment and trending of cardiac output a viable alternative to assist in the management of both chronically and acutely ill patients, including those with heart failure. [source] Flow cytometry for ZAP-70: New colors for chronic lymphocytic leukemiaCYTOMETRY, Issue 4 2006Adrian Wiestner Abstract ZAP-70 has become one of the most studied prognostic markers in Chronic Lymphocytic Leukemia (CLL). ZAP-70 is remarkable in many ways: ZAP-70 has been identified as the best discriminating gene between prognostically distinct CLL subtypes using large scale gene expression profiling; ZAP-70 has been shown to enhance signal transduction in CLL B-cells and therefore could contribute to disease progression; and ZAP-70 is one of the rare examples of an intracellular target considered for clinical flow cytometry. This issue attests to the enormous effort and the steady progress made in overcoming technical challenges of testing for ZAP-70 expression and sets the foundation for a successful translation of this important marker into clinical practice. Despite the best effort, one will likely have to accept that not all cases can be clearly assigned to one or the other group, given that ZAP-70 expression between CLL patients falls along a continuum from absent to high. Nevertheless, ZAP-70 expression could become a key parameter to guide patients towards risk adapted treatment strategies in prospective clinical trials. © 2006 International Society for Analytical Cytology [source] Increased immature hematopoietic progenitor cells CD34+/CD38dim in myelodysplasiaCYTOMETRY, Issue 2 2006Mariela B. Monreal Abstract Background Myelodysplastic syndromes (MDS) are clonal disorders affecting hematopoietic progenitor cells (HPC). Despite the relevance of clonal CD34+ cells in developing MDS, only few studies analyze the phenotype of this cell population. The aim of this study was to evaluate phenotypic changes on HPC in MDS that could reflect abnormalities in the differentiation process of stem cells. Methods We analyzed the expression of CD38 and HLA-DR on CD34+ cells by flow cytometry in 36 patients with MDS, as well as in healthy donors (n = 12) and patients with other hematological disorders: non-Hodgkin lymphomas and multiple myeloma, both in complete remission (CR) (n = 32); acute lymphoblastic leukemia in CR (n = 17); de novo acute myeloblastic leukemia (AML) at diagnosis (n = 22) and in CR (n = 37); and AML secondary to MDS at diagnosis (n = 19). Cases with available karyotype were grouped according to the International Prognostic Scoring System (IPSS). Results Compared to normal BM, the fraction of immature HPC, characterized as CD34+bright, intermediate FSC/SSC, and CD38dim, was significantly increased in high risk MDS and secondary AML, but not in low risk MDS, (P , 0.001, P = 0.03, and P = 0.7). De novo AML showed decreased immature HPC. High numbers of immature HPC correlated with higher IPSS risk groups (P = 0.05) and showed significant impact on disease progression (P = 0.03). Conclusion Our study confirms that evaluation of CD38 expression pattern on HPC is an easy and reproducible test that allows evaluating the immature subset of progenitor cells. Increased immature HPC in high risk MDS and secondary AML may reflect blocked differentiation of CD34+ cells in these diseases. © 2006 International Society for Analytical Cytology [source] Impact of the international program for quality assessment and standardization for immunological measures relevant to HIV/AIDS: QASICYTOMETRY, Issue 2 2002Francis Mandy Abstract Measurements of CD4 T-cell levels are essential for the assessment of human immunodeficiency virus (HIV) disease course, clinical staging, epidemiological studies, and decisions regarding prophylactic therapies against opportunistic infection. Until now, only in the industrialized countries was T-cell subset monitoring considered a practical option to assess disease progression. The Quality Assessment and Standardization for Immunological Measures Relevant to HIV/AIDS (QASI) program was established in 1997 to meet performance assessment for immunophenotyping laboratories in countries where such service is not available. The QASI program is provided at no cost to any laboratory in a resource-poor setting that wishes to participate. This report describes the beneficial impact of participation in the QASI program. Carefully selected commercial stabilized whole blood preparations were sent regularly to participating laboratories. Participants reported the T-cell subset values they obtained by flow cytometry. Once the aggregate mean values for the T-cell subsets were established for the shipment, a comprehensive and confidential report was sent to each laboratory. The results from five consecutive shipments were analyzed. The coefficient of variation decreased from 7.2% to 4.7% and from 14.2% to 8.8% for percent and absolute CD4 T-cell counts, respectively. With the implementation of the QASI program using commercial stabilized whole blood specimens, it is possible to reduce interlaboratory error. This study illustrates that a quality assessment program can improve the overall performance of laboratories. Reducing interlaboratory variation can enhance significantly the effectiveness of multicenter HIV vaccine or drug trial evaluation. Cytometry (Clin. Cytometry) 50:111,116, 2002. © 2002 Wiley-Liss, Inc. [source] Human immunodeficiency virus gag and pol-specific CD8 T cells in perinatal HIV infectionCYTOMETRY, Issue 5 2001Thomas W. McCloskey Abstract Background: Binding of fluorochrome-conjugated MHC class I tetramers is a powerful means to detect antigen-specific CD8 T lymphocytes. In human immunodeficiency virus (HIV) infection, cellular immune response is essential in curtailing HIV disease progression but gaps persist in our understanding of HIV-specific cells during the disease course. In this study, we evaluated tetramer binding HIV-specific CD8 T cells in HIV-infected children. Methods: Fluorescently labeled tetramers for HIV gag and pol were utilized to quantify antigen-specific cells by flow cytometry using a whole blood labeling method in a cohort of 19 HLA-A2+ HIV- infected children (age range 1 month to 17 years). Results: Fourteen children had detectable gag (median 0.4%) and pol (median 0.1%) binding CD8 T cells, three children had gag binding cells only, and two had neither. Numbers of gag and pol binding cells correlated with each other and each correlated independently with total CD8 T cells and total CD4 T cells. Conclusions: HIV gag and pol-specific CD8 T cells are maintained during the chronic phase of HIV infection in children and CD4 lymphocytes appear to be important for sustaining their levels. Cytometry (Comm. Clin. Cytometry) 46:265,270, 2001. © 2001 Wiley-Liss, Inc. [source] Topical tacrolimus in the management of atopic dermatitis in JapanDERMATOLOGIC THERAPY, Issue 2 2006Masutaka Furue ABSTRACT:, Atopic dermatitis (AD) is a common, chronic, relapsing, severely pruritic, eczematous skin disease. Topical steroids are the mainstay of treatment. However, the adverse effects of steroids on hormonal function are the major obstacle for their use as long-term topical therapy. Topical calcineurin inhibitors, such as tacrolimus, not only complement existing treatment options but also overcome some of the drawbacks of topical steroid therapy and fulfill the long-term needs of patients in preventing disease progression. Short- and long-term efficacy and safety of topical tacrolimus has been widely recognized and it is also accepted as a first-line treatment for the inflammation of AD. In order to reduce the possible long-term adverse effects, it is important to monitor the clinical dose in daily clinics. [source] The role of weight for age and disease stage in poor psychomotor outcome of HIV-infected children in Kilifi, KenyaDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 12 2009AMINA ABUBAKAR PHD Aim, We aimed to investigate the contribution of disease stage and weight for age to the variability in psychomotor outcome observed among children with human immunodeficiency virus (HIV) infection. Method, This cross-sectional study involved 48 Kenyan children (20 females, 28 males) aged 6 to 35 months (mean 19.9mo SD 8.9) exposed prenatally to HIV. Two subgroups of HIV-exposed children were seen: those who were HIV-infected and those who were uninfected. The reference population was composed of 319 children (159 females, 160 males) aged 6,35 months, (mean age = 19 months, SD=8.43) randomly selected from the community. Disease stage varied from stage 1 to stage 3, reflecting progression from primary HIV infection to advanced HIV infection and acquired immune deficiency syndrome. A locally developed and validated measure, the Kilifi Developmental Inventory, was used to assess psychomotor development. Result, Using age-corrected psychomotor scores, a significant main effect of HIV status was observed (F(2,38.01)=7.89, p<0.001). Children in the HIV-infected group had lower mean psychomotor scores than the HIV-exposed children and the reference group. In the HIV-infected group, disease stage was a negative predictor and weight for age a positive predictor of psychomotor outcome. Interpretation, Weight for age and disease stage provide viable, easily measurable benchmarks to specify when frequent developmental monitoring and psychomotor rehabilitation are required. Nutritional intervention and other measures aimed at slowing disease progression may delay the onset and severity of psychomotor impairment in the paediatric HIV population in Africa. [source] Vascular endothelial growth factor prevents G93A-SOD1-induced motor neuron degenerationDEVELOPMENTAL NEUROBIOLOGY, Issue 13 2009J. Simon Lunn Abstract Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by selective loss of motor neurons (MNs). Twenty percent of familial ALS cases are associated with mutations in Cu2+/Zn2+ superoxide dismutase (SOD1). To specifically understand the cellular mechanisms underlying mutant SOD1 toxicity, we have established an in vitro model of ALS using rat primary MN cultures transfected with an adenoviral vector encoding a mutant SOD1, G93A-SOD1. Transfected cells undergo axonal degeneration and alterations in biochemical responses characteristic of cell death such as activation of caspase-3. Vascular endothelial growth factor (VEGF) is an angiogenic and neuroprotective growth factor that can increase axonal outgrowth, block neuronal apoptosis, and promote neurogenesis. Decreased VEGF gene expression in mice results in a phenotype similar to that seen in patients with ALS, thus linking loss of VEGF to the pathogenesis of MN degeneration. Decreased neurotrophic signals prior to and during disease progression may increase MN susceptibility to mutant SOD1-induced toxicity. In this study, we demonstrate a decrease in VEGF and VEGFR2 levels in the spinal cord of G93A-SOD1 ALS mice. Furthermore, in isolated MN cultures, VEGF alleviates the effects of G93A-SOD1 toxicity and neuroprotection involves phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling. Overall, these studies validate the usefulness of VEGF as a potential therapeutic factor for the treatment of ALS and give valuable insight into the responsible signaling pathways and mechanisms involved. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Post-challenge glucose predicts coronary atherosclerotic progression in non-diabetic, post-menopausal women,DIABETIC MEDICINE, Issue 10 2007P. B. Mellen Abstract Aims, We sought to determine whether fasting or post-challenge glucose were associated with progression of coronary atherosclerosis in non-diabetic women. Methods, We performed a post-hoc analysis of 132 non-diabetic women who underwent 75-g oral glucose tolerance testing. The primary outcome of interest was progression of atherosclerosis determined by baseline and follow-up coronary angiography, a mean of 3.1 ± 0.9 years apart. We analysed the association of change in minimal vessel diameter (,MD) by quartile of fasting and post-challenge glucose using mixed models that included adjustment for age, systolic blood pressure, total : high-density lipoprotein cholesterol ratio, current smoking, lipid-lowering and anti-hypertensive medication use and other covariates. Results, At baseline, participants had a mean age of 65.7 ± 6.7 years and a mean body mass index of 27.9 ± 8.5 kg/m2. Although there were no significant differences in atherosclerotic progression by fasting glucose category (P for trend across quartiles = 0.99), there was a significant inverse association between post-challenge glucose and ,MD (in mm) (Q1 : 0.01 ± 0.03; Q2 : 0.08 ± 0.03; Q3 : 0.13 ± 0.03; Q4 : 0.11 ± 0.03; P for trend = 0.02). Conclusions, In post-menopausal women without diabetes, post-challenge glucose predicts angiographic disease progression. These findings suggest that even modest post-challenge hyperglycaemia influences the pathogenesis of atherosclerotic progression. [source] Preservation of sight in diabetes: developing a national risk reduction programmeDIABETIC MEDICINE, Issue 9 2000L. Garvican SUMMARY Background Early treatment for diabetic retinopathy is effective at saving sight, but dependent on pre-symptomatic detection. Although 60% of people with diabetes have their eyes examined annually, few UK health authorities have systematic programmes that meet the British Diabetic Association's standards for sensitivity (> 80%) and specificity (> 95%). Screening is generally performed by general practitioners and optometrists, with some camera-based schemes, operated by dedicated staff. The National Screening Committee commissioned a group to develop a model and cost estimates for a comprehensive national risk-reduction programme. Ophthalmoscopy Evidence indicates that direct ophthalmoscopy using a hand-held ophthalmoscope does not give adequate specificity and sensitivity, and should be abandoned as a systematic screening technique. Indirect ophthalmoscopy using a slit lamp is sensitive and specific enough to be viable, and widespread availability in high street optometrists is an advantage, but the method requires considerable skill. Photographic schemes The principal advantage of camera-based screening is the capturing of an image, for patient education, review of disease progression, and quality assurance. Digital cameras are becoming cheaper, and are now the preferred option. The image is satisfactory for screening and may be transmitted electronically. With appropriate training and equipment, different professional groups might participate in programme delivery, based on local decisions. Cost issues Considerable resources are already invested in ad hoc screening, with inevitable high referral rates incurring heavy outpatient costs. Treatment for advanced disease is expensive, but less likely to be effective. The costs of a new systematic screening and treatment programme appear similar to current expenditure, as a result of savings in treatment of late-presenting advanced retinopathy. Conclusion A systematic national programme based on digital photography is proposed. [source] The role of surveillance endoscopy and endosonography after endoscopic ablation of high-grade dysplasia and carcinoma of the esophagusDISEASES OF THE ESOPHAGUS, Issue 2 2008A. D. Savoy SUMMARY., Barrett's esophagus (BE) with high-grade dysplasia (HGD) or early carcinoma treated with surgery or photodynamic therapy (PDT) is at risk of recurrence. The efficacy of endoscopic ultrasound (EUS) for surveillance after PDT is unknown. Our objective was to determine if EUS is superior to esophagogastroduodenoscopy (EGD) and/or CT scan for surveillance of BE neoplasia after PDT. The study was designed as a retrospective review with the setting as a tertiary referral center. Consecutive patients with BE with HGD or carcinoma in situ treated with PDT were followed with EUS, CT scan and EGD with jumbo biopsies every 1 cm at 3, 4, or 6-month intervals. Exclusion criteria was < 6 months of follow up and/or < 2 EUS procedures. Main outcome measurements were residual or recurrent disease discovered by any method. Results showed that 67/97 patients met the inclusion criteria (56 men and 11 women). Median follow-up was 16 months. Recurrent or residual adenocarcinoma (ACA) was detected in four patients during follow-up. EGD with random biopsies or targeted nodule biopsies detected three patients. EUS with endoscopic mucosal resection of the nodule confirmed T1 recurrence in one of these three. In the fourth patient, CT scan revealed perigastric lymphadenopathy and EUS-FNA (fine needle aspiration) confirmed adenocarcinoma. There were two deaths, one related to disease progression and one unrelated. The rate of recurrent/persistent ACA after PDT was 4/67 = 6%. EUS did not detect disease when EGD and CT were normal. Limitations of this study include non-blinding of results and preferential status of non-invasive imaging (CT) over EUS. Our experience suggests that EUS has little role in the surveillance of these patients, unless discrete abnormalities are found on EGD or cross-sectional imaging. [source] Preoperative chemoradiotherapy in cancer of the thoracic esophagusDISEASES OF THE ESOPHAGUS, Issue 1 2003G. Terrosu SUMMARY. Surgery with or without adjuvant radiotherapy (RT) is the standard treatment of esophageal cancer. Preoperative radio- and chemotherapy (CT) have been introduced to improve prognosis. We report a phase II prospective non-randomized trial of preoperative RT (42 Gy/25) plus CT (cisplatin 20 mg/mq/day plus 5-fluorouracil 600 mg/mq/day, 1,5 weeks) for the treatment of thoracic esophageal cancer. From 1993, 50 patients were enrolled (40 men and 10 women, mean age 57 years, range 30,75 years). Squamous cell carcinoma accounted for 90% of cases; 10% were adenocarcinoma. Downstaging of the disease was obtained in 77.3% of cases; there were 13 (29.5%) complete responses (CR) and 21 (47.7%) partial responses (PR). Median survival was 28 and 25 months, respectively, for CR and partial response (PR) plus stable disease (SD) and progressive disease (PD) (P = 0.05). Progressive-free median survival was 22 and 17 months, respectively, for CR and PR + SD + PD (P = 0.08). Multimodal treatment of esophageal cancer showed promising results, although not significant, in terms of survival and disease progression for patients achieving a complete pathologic response. [source] | |||||||||||||||||||||||||||||||||||||