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Slow Progression (slow + progression)
Selected AbstractsScreening for Asymptomatic Left Ventricular Dysfunction Using B-Type Natriuretic PeptideCONGESTIVE HEART FAILURE, Issue 2008Theresa A. McDonagh MD Asymptomatic left ventricular dysfunction (ASLVD), a known precursor phase of heart failure, fulfills the essential criteria that should be met before screening for a disease. It is common and associated with reduced longevity and quality of life. Left untreated, it progresses to heart failure, which incurs a mortality greater than most cancers as well as significant morbidity rates. In addition, we now have several population-based studies that demonstrate that both B-type natriuretic peptide (BNP) and N-terminal prohormone brain natriuretic peptide (NTproBNP) can accurately exclude left ventricular systolic dysfunction. More recent work shows that this can be done cost-effectively. There is also a wealth of evidence from randomized controlled trials indicating that the treatment of ASLVD can reduce both morbidity and mortality and slow progression to the heart failure state. The main stumbling block to implementation of screening, in addition to the perceived cost, may well be the lack of a randomized study showing that screening the population for ASLVD really does alter the natural history of the condition, something that other screening strategies have so far failed to do. Congest Heart Fail. 2008;14(4 suppl 1):5,8. ©2008 Le Jacq [source] Medium-term outcome of fundoplication after lung transplantationDISEASES OF THE ESOPHAGUS, Issue 8 2009P. R. Burton SUMMARY Gastroesophageal reflux disease (GERD) in lung transplant recipients has gained increasing attention as a factor in allograft failure. There are few data on the impact of fundoplication on survival or lung function, and less on its effect on symptoms or quality of life. Patients undergoing fundoplication following lung transplantation from 1999 to 2005 were included in the study. Patient satisfaction, changes in GERD symptoms, and the presence of known side effects were assessed. The effect on lung function, body mass index, and rate of progression to the bronchiolitis obliterans syndrome (BOS) were recorded. Twenty-one patients (13 males), in whom reflux was confirmed on objective criteria, were included, with a mean age of 43 years (range 20,68). Time between transplantation and fundoplication was 768 days (range 145,1524). The indication for fundoplication was suspected microaspiration in 13 and symptoms of GERD in 8. There was one perioperative death, at day 17. There were three other late deaths. Fundoplication did not appear to affect progression to BOS stage 1, although it may have slowed progression to stage 2 and 3. Forced expiratory volume-1% predicted was 72.9 (20.9), 6 months prior to fundoplication and 70.4 (26.8), six months post-fundoplication, P= 0.33. Body mass index decreased significantly in the 6 months following fundoplication (23 kg/m2 vs. 21 kg/m2, P= 0.05). Patients were satisfied with the outcome of the fundoplication (mean satisfaction score 8.8 out of 10). Prevalence of GERD symptoms decreased significantly following surgery (11 of 14 vs. 4 of 17, P= 0.002). Fundoplication does not reverse any decline in lung function when performed at a late stage post-lung transplantation in patients with objectively confirmed GERD. It may, however, slow progression to the more advanced stages of BOS. Reflux symptoms are well controlled and patients are highly satisfied. Whether performing fundoplication early post-lung transplant in selected patients can prevent BOS and improve long-term outcomes requires formal evaluation. [source] Cerebral hemiatrophy with superficial siderosis and PLEDs due to a germ cell tumor of the basal gangliaEUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2006N. Kumar The diagnosis of basal ganglia germ cell tumors may be delayed due to slow progression and minimal early changes on magnetic resonance imaging (MRI). The cystic nature of some tumors may lead to non-diagnostic biopsies. We describe the clinical, imaging, laboratory, and postmortem findings of a basal ganglia germ cell tumor in a 19-year-old man. Clues to an early antemortem diagnosis based on MRI findings and determination of tumor markers are discussed. An early diagnosis and accurate characterization of basal ganglia germ cell tumors is essential for optimal therapy. The presence of cerebral hemiatrophy and hemorrhagic or cystic components is suggestive. Measurement of serum and cerebrospinal fluid markers such as human chorionic gonadotropin may suggest the diagnosis. [source] Long-term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birthHEPATOLOGY, Issue 1 2004Maria Antonietta Casiraghi Long-term follow up studies of hepatitis C virus (HCV) infection rarely exceed 20,25 yr. We studied the outcome of HCV infection in 35-yr-old adults infected at birth (1968) through mini transfusions of blood. A retrospective-prospective study was carried out. The cohort included 31 individuals who were given mini blood transfusions (21,30 ml) collected from a donor subsequently revealed to be HCV infected. At enrollment (1998), 18 of 31 (58.1%) recipients had anti-HCV antibody and 16 (88.9%) of them were HCV-RNA positive. All viremic recipients and the infectious donor had the same genotype 1b. Sequence analysis of E1/E2 and NS5b regions, coupled with phylogenetic analysis, indicated that HCV isolates from donor/recipients were linked. Eleven of the 16 viremic recipients gave consent to liver biopsy. Nine had no fibrosis or mild portal fibrosis and 2 had either discrete (Ishak's staging 3) or marked (Ishak's staging 4) fibrosis. During the prospective follow-up period (1998,2003), 2 patients were given therapy, one of whom achieved sustained clinical and virologic response. A second biopsy, performed in 5 patients at a 5 yr interval, revealed no substantial modifications in 4 cases and progression from absence of fibrosis to mild portal fibrosis in the fifth. In conclusion, taking into account the limited study sample, these findings suggest that HCV infection acquired early in life shows a slow progression and mild outcome during the first 35 yr of infection. (HEPATOLOGY 2004;39:90,96.) [source] Slowed Progression or Elimination of Atherosclerosis by Low-Frequency Electrical ImpulsesJOURNAL OF CARDIAC SURGERY, Issue 1 2003Ph.D., Valeri Chekanov M.D. In this investigation we demonstrated the slow progression or elimination of atherosclerosis by low-frequency EI in case of moderate atherosclerosis (after eight weeks of HCD). Methods: Series I rabbits (control group) were fed HCD for eight weeks. Series II rabbits were fed HCD for eight weeks and were then switched to normal diet for eight weeks (no EI). Series III rabbits were fed HCD for eight weeks and then switched to a normal diet with simultaneous EI (applied near the abdominal aorta) for eight weeks (3 V, 30 single impulses per minute, 24 hours/day). After euthanization, the level of atherosclerosis, percentage of surface area involved in the atherosclerosis process, and an atherosclerosis score were calculated in the aortic arch, thoracic and abdominal aorta. Results: Statistically significant differences were seen in the level of atherosclerosis in the abdominal aorta between series III animals (0.4 ± 0.2) and the other two groups: 1.5 ± 0.4 in series I (HCD only), 1.2 ± 0.3 in series II (HCD then normal diet). Gross examination of the surface also revealed statistically significant differences (p < 0.05) in the percentage of atherosclerosis between the control series I (30.1 ± 4.1%) and series II (21.3 ± 3.6%), compared with series III (5.5 ± 5.4%). In addition, the atherosclerosis score was also significantly different: 45.8 ± 3.9 in series I, 25.2 ± 6.9 in series II, and 2.2 ± 2.0 in series III (p < 0.05). Conclusion: Our study showed that, when applied near the abdominal aorta, low-frequency electrical impulses decrease atherosclerotic deposition in the abdominal aorta. (J Card Surg 2003; 18:47-58) [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] Chronic exposure to nicotine and saquinavir decreases endothelial Notch-4 expression and disrupts blood-brain barrier integrityJOURNAL OF NEUROCHEMISTRY, Issue 2 2010Vamshi K. Manda J. Neurochem. (2010) 115, 515,525. Abstract Since the advent of HAART, there have been substantial improvements in HIV patient survival; however, the prevalence of HIV associated dementia has increased. Importantly, HIV positive individuals who smoke progress to HIV associated neurological conditions faster than those who do not. Recent in vitro data have shown that pharmacological levels of saquinavir causes endothelial oxidative stress and significantly decreases Notch-4 expression, a primary protein involved in maintaining stability of blood-brain barrier (BBB) endothelium. This is concerning as nicotine can also generate reactive oxygen species in endothelium. It is largely unknown if pharmacological doses of these drugs can cause a similar in vivo down-regulation of Notch-4 and if there is a concurrent destabilization of the integrity of the BBB. The data herein show: (i) nicotine and protease inhibitors cause an additive oxidative stress burden in endothelium; (ii) that the integrity of the BBB is disrupted after concurrent chronic nicotine and protease inhibitor administration; and (iii) that BBB endothelial dysfunction is correlated with a decrease in Notch-4 and ZO-1 expression. Considering the high prevalence of smoking in the HIV infected population (3- to 4-fold higher than in the general population) this data must be followed up to determine if all protease inhibitors cause a similar BBB disruption or if there is a safer alternative. In addition, this data may suggest that the induced BBB disruption may allow foreign molecules to gain access to brain and be a contributing factor to the slow progression of HIV associated dementia. [source] MAPK-pathway activity, Lrrk2 G2019S, and Parkinson's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2007Linda R. White Abstract The 6055G>A mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in a G2019S substitution in the mixed-lineage kinase domain of Lrrk2, causing autosomal dominant Parkinson's disease (PD). We hypothesized the mutation alters cellular mitogen-activated protein kinase (MAPK) signalling cascades, and might be detectable in tissues other than in the brain. We therefore compared total levels and activation of the signalling proteins Src, HSP27, p38 MAPK, JNK, and ERK, in extracts of leukocytes isolated from patients with PD carrying the G2019S mutation, healthy mutation carriers, patients with idiopathic PD, and healthy controls. Phosphorylation of Src, HSP27, and JNK was reduced significantly in cell extracts from patients with G2019S-associated PD compared to healthy controls. Similarly, phosphorylation was reduced significantly in Src and HSP27 in the group of healthy carriers of the mutation, as well as in patients with idiopathic PD. Significant reductions in total Src were also observed in these three groups compared to the controls. The results of this pilot project therefore indicate significant alterations in key signalling proteins in leukocytes from patients with PD, and were most pronounced in G2019S-associated PD. Changes in MAPK-signalling may thus be common to PD pathophysiology, regardless of aetiology. Such changes may also be shown in blood samples during the preclinical stage of LRRK2 -associated PD, which could be particularly important for the development of neuroprotective strategies to delay onset, or slow progression of PD. © 2007 Wiley-Liss, Inc. [source] Genetic variability of hepatitis C virus NS3 protein in human leukocyte antigen-A2 liver transplant recipients with recurrent hepatitis CLIVER TRANSPLANTATION, Issue 2 2004F. Xavier López-Labrador The association between the severity of chronic hepatitis C and the variability of the hepatitis C virus (HCV) genome remains controversial, but to our knowledge few data are available to date regarding T-cell epitope coding regions in transplant patients. In the current study, we identified 21 human leukocyte antigen (HLA)-A2-positive Spanish patients with chronic hepatitis C, 14 immunosuppressed liver transplant recipients, and 7 immunocompetent controls. Alanine aminotransferase, aspartate aminotransferase, viral load, and rate of fibrosis progression were determined. Genetic distances of HCV isolates and variations in epitopes of the HCV nonstructural 3 protein (NS3-1393 LIFCHSKKK and NS3-1406 KLVALGINAV) were compared between patients with slow or fast progression of fibrosis. Isolates from transplant patients with fast progression were found to be more divergent (P =.03), had a higher mean value of synonymous (dS) variations (P =.02), and some were differentiated in a phylogenetic tree, compared with isolates from patients with slow progression. The HLA-A2-restricted NS3-1406 epitope was found to be more variable (20 of 21 isolates differed from the prototype) compared with the A3-restricted NS3-1392 epitope (19% vs. 1.25% variation). A shift in the viral peptide was not detected in a subset of transplant patients, but was evident in two of three nontransplant patients with follow-up. There was no correlation noted between a particular amino acid variation and fibrosis progression (slow or fast) in either transplant or nontransplant patients. The results of the current study suggest that 1) there may be different HCV-1b strains in our geographic area, 2) immunosuppression appears to have little effect in amino acid variation at the HCV NS3-1406 epitope, and 3) variations over time might be more frequent in nonimmunosuppressed patients. (Liver Transpl 2004;10:217,227.) [source] MM2-cortical-type sporadic Creutzfeldt-Jakob disease with early stage cerebral cortical pathology presenting with a rapidly progressive clinical courseNEUROPATHOLOGY, Issue 6 2008Yoshiki Niimi We report the case of a 67-year-old man with MM2-cortical-type sporadic Creutzfeldt-Jakob disease (sCJD) with a rapidly progressive clinical course of 5 months. Initial symptoms were progressive memory disturbance and dementia. MRI revealed high signal-intensity lesions on diffusion-weighted images in the bilateral frontal and occipital cortices. Myoclonus and periodic sharp-wave complexes on the electroencephalogram were observed in the early disease stage. The clinical diagnosis was typical sCJD. Neuropathologic examination at autopsy showed widespread, characteristic cerebral neocortical involvement with large confluent vacuole-type spongiform change. Spongiform degeneration was also evident in the striatum and medial thalamus. In the cerebellar cortex, slight depletion of Purkinje neurons was evident without spongiform change in the molecular layer or apparent neuron loss in the granule cell layer. The inferior olivary nucleus showed slight hypertrophic astrocytosis without neuron loss. Prion protein (PrP) immunostaining showed widespread, characteristic perivacuolar-type PrP deposits with irregular plaque-like PrP deposits in the cerebral neocortex, striatum and medial thalamus. We believe this patient showed early-stage cerebral cortical pathology of MM2-cortical-type sCJD, which may provide clues regarding the pathologic progression of this rare sCJD subtype. Although MM2-cortical-type sCJD generally shows slow progression without myoclonus or periodic sharp-wave complexes, the present patient showed a rapidly progressive clinical course similar to that of MM1-type sCJD. [source] Multinucleated astrocytes in old demyelinated plaques in a patient with multiple sclerosisNEUROPATHOLOGY, Issue 3 2004Makoto Nishie A 51-year-old woman with MS of 26 years duration is reported. The patient's MS history began at the age of 25 years with an initial relapsing-remitting course, followed by slow progression without distinct relapses. She became bed-ridden at the age of 40 years. A post-mortem examination revealed numerous demyelinated plaques that exhibited fibrillary gliosis with Rosenthal fibers, but without lymphocytic cuffing or foamy macrophages. Activated microglia were found mainly in the marginal portion of the plaques. These plaques were consistent with so-called ,slowly expanding plaques'. Interestingly, multinucleated astrocytes were observed within the plaques, being more numerous in the area where microglial infiltration had occurred. These findings suggest that mild persistent inflammatory processes are present even in old plaques and that certain inflammatory stimuli cause multinucleation of astrocytes. This might explain the gradual deterioration without definite relapses observed in the late stage of MS. [source] Latest news and product developmentsPRESCRIBER, Issue 18 2008Article first published online: 3 OCT 200 Inhaled steroids for all children with asthma? Some children with mild well-controlled asthma may not need a daily inhaled steroid, a Scandinavian study suggests (Arch Dis Child 2008;93:654-9). A total of 176 children aged 5-10 years were randomised to treatment with cromoglicate (Intal) or budesonide. Initially high doses of budesonide (400,g twice daily) were reduced after one month to 200,g twice daily for four months; subsequent treatment for a further year was 100,g twice daily as required for exacerbations or 100,g twice daily regularly. Budesonide was associated with greater improvement in lung function and fewer exacerbations compared with cromoglicate, but after 18 months lung function improvements did not differ. Regular budesonide was associated with fewer exacerbations than as-required administration (0.97 vs 1.69 per patient in months 7-18) but no difference in asthma-free days or use of rescue medication. Growth suppression was slightly greater with continuous budesonide. Interventions to reduce atypicals weight gain A systematic review has found that techniques such as cognitive behaviour therapy and nutritional counselling can reduce weight gain associated with atypical antipsychotics (Br J Psychiatry 2008;193:101-7). Analysis of 10 randomised trials lasting eight weeks to six months found that nonpharmacological intervention increased mean weight loss by about 2.5kg compared with usual care. Check flu vaccine delivery Production of flu vaccine is proceeding according to plan, the Director of Immunisation has told GPs. Practices should now contact their suppliers to confirm a delivery schedule so that clinics can be arranged. New BNF for Children The fourth BNF for Children has been published, containing new sections on HPV vaccination, contraception, treatment of pelvic inflammatory disease and the use of continuous iv infusions in neonates. BNFC 2008 is available online at bnfc.org/bnfc. MMR catch-up ,urgent' The DoH has called for urgent action to reduce the risk of a measles epidemic. Following years of relatively low uptake of MMR vaccine, the pool of unprotected children is now large enough to raise the prospect of 30 000-100 000 measles cases in England. A catch-up campaign will now target children and young people who have never been vaccinated, followed by those who have not completed their course of immunisation. Resource materials are available at www.immunisation.nhs.uk. , A new brand of MMR vaccine is now available. Sanofi Pasteur MSD has replaced MMRII with a new formulation and presentation, MMRvaxPro. The new vaccine is equivalent to its predecessor and interchangeable with Priorix. Early primary prevention with low-dose aspirin? GPs should consider prescribing low-dose aspirin for primary prevention for men aged 48 and women aged 57, say UK researchers (Heart 2008; published online 15 August 2008. doi:10.1136/hrt.2008.150698). Using data from the THIN network of electronic patient records, they modelled the age at which 10-year coronary risk changed from <10 per cent to >10 per cent in men and women without diabetes, not taking lipid-lowering therapy and with no history of cardiovascular disease. Does COPD therapy slow progression? Treatment with an inhaled steroid and long-acting beta-agonist may slow progression of COPD, according to a new analysis of the TORCH study (Am J Respir Crit Care Med 2008;178:332-8). TORCH was designed to determine the effects of COPD treatment on mortality; the primary analysis found no significant difference between fluticasone/salmeterol (Seretide) and placebo (N Engl J Med 2007;356:775-89). This analysis found that the rate of decline in FEV1 (a marker of disease progression) was significantly greater with placebo (55ml per year) than with salmeterol or fluticasone monotherapy (both 42ml per year) or their combination (39ml per year). Faster decline in FEV1 was associated with current smoking, lower BMI and more frequent exacerbations. Copyright © 2008 Wiley Interface Ltd [source] Late onset cerebellar cortical degeneration in a koalaAUSTRALIAN VETERINARY JOURNAL, Issue 8 2009M Kuwamura A 10-year-old male koala started to fall from the tree while sleeping. Subsequently, the koala often fell down while walking and showed a gait abnormality, abnormal nystagmus and hypersalivation. At 12 years of age, the koala became ataxic and seemed blind. At 13 years of age, the koala exhibited signs of dysstasia and was euthanased. Necropsy revealed marked symmetrical atrophy of the cerebellum. Histopathologically, a severe loss of Purkinje and granule cells was evident in the cerebellum, while the molecular layer was more cellular than normal with cells resembling small neurons, which were positively stained with parvalbumin immunohistochemistry. Reactive Bergmann glial cells (astrocytes) were present adjacent to the depleted Purkinje cell zone. The very late onset and slow progression of the cerebellar cortical degeneration in this case is particularly interesting and appears to be the first report in the koala. [source] Axonal and demyelinating forms of the MPZ Thr124Met mutationACTA NEUROLOGICA SCANDINAVICA, Issue 3 2003S. Kurihara Objective , We report on a Japanese family with Charcot,Marie,Tooth disease (CMT) with the Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene. Material and methods , Based on the clinical study, we investigated MPZ gene by direct sequence analysis and polymerase chain reaction,restriction fragment length polymorphism analysis. Results , Genotyping of four symptomatic family members showed that one family member with severe disease symptoms was homozygous, while the other three were heterozygous. The heterozygous cases were clinicopathologically determined to be the axonal type, which is characterized by late-onset and slow progression associated with Adie's pupil and deafness. The homozygous case was the demyelinating type, which showed earlier onset, rapid progression, sural nerve demyelination, and cranial nerve demyelination at autopsy. Conclusions , We suggest that axonal and demyelinating forms of CMT are not two distinct classes, but rather parts of a spectrum of genotypically related conditions, particularly with some MPZ mutations. [source] Developments in the management of mycetomasCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2009M. Ameen Summary Mycetomas are chronic, granulomatous, subcutaneous infections caused by either eumycetes fungi or actinomycetes bacteria, giving rise to eumycetomas and actinomycetomas, respectively. The disease is endemic in many tropical countries, and is characterized by slow progression with risks of bone and visceral involvement. Treatment consists of long courses of antifungals and antibacterials, often combined with surgery. Drug resistance, poor response to treatment, and high rates of relapse have prompted trials of novel antibiotics and antifungals. This article discusses the potential of new treatment regimens and recent developments and improvements in diagnostics and prognostics, which will improve disease management. [source] Treatment of chronic hepatitis C virus infection in patients with cirrhosisJOURNAL OF VIRAL HEPATITIS, Issue 5 2000Zeuzem Chronic hepatitis C virus (HCV) infection eventually leads to cirrhosis in 20,30% of patients and to hepatocellular carcinoma (HCC) in 1,5% of patients. Rates of sustained virological response with standard interferon-, (IFN-,) are low in patients without cirrhosis (generally < 20%) and are even lower in those with cirrhosis. Combination therapy with IFN and ribavirin improves response rates in patients with chronic hepatitis C without cirrhosis, and the results from subgroups of HCV-infected patients with advanced fibrosis or cirrhosis are encouraging. Importantly, treatment with IFN slows progression of liver fibrosis, regardless of HCV genotype or early response to therapy, and reduces the risk of HCC by two- to fivefold. The risk of development of HCC is also lower in patients who show at least a partial response to IFN therapy compared with those who show no response. There is a clear need for more definitive studies of treatment in patients with chronic hepatitis C and cirrhosis, ideally using therapies with greater efficacy. Nonetheless, based on the potential to slow the progression of liver fibrosis (regardless of treatment response) and to reduce the risk of HCC, a greater number of HCV-infected patients with cirrhosis should be considered as candidates for IFN treatment. Preliminary data indicate that pegylated IFNs have improved virological response rates and may have additional clinical benefits in the prevention or reduction of fibrosis and retardation of progression of cirrhosis and HCC in these patients. 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