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PubMed2006

Mesenchymal lineage precursor cells induce vascular network formation in ischemic myocardium.

Mesenchymal lineage precursors can be reproducibly isolated from adult mammalian bone marrow and grown in culture. Immunoselection with monoclonal antibodies against STRO-1 and vascular-cell-adhesion molecule 1 (VCAM1/CD106) prior to expansion results in a 1,000-fold enrichment of mesenchymal precursors compared to standard isolation techniques. Intramyocardial injection of human STRO-1-selected precursors in an athymic rat model of acute myocardial infarction results in induction of vascular network formation and arteriogenesis coupled with global functional cardiac recovery.

ADP-ribosyl Cyclase↗

PubMed2004

Proteomics in postgenomic neuroscience: the end of the beginning.

Proteomics is complementary to genomic approaches anchored in DNA and RNA. Global characterization of proteins is providing new insights into general biological structures as well as synapses, receptor complexes and other neuronal and glial features. Current challenges for proteomics of the nervous system include problems relating to sample preparation, brain complexity, limited databases and informatics tools. The combination of proteomics with other global functional genomic approaches at the levels of genome and transcriptome, together with network biology, will provide important bridges between genes, physiology and pathology.

Animals↗

PubMed2005

A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment.

Inflammatory mechanisms have been implicated in Alzheimer's disease (AD) and might be mediated via the COX-2 enzyme. Previous studies with the selective COX-2 inhibitors, rofecoxib and celecoxib, have shown that they do not alter the progression of AD. We conducted a double-blind study to investigate whether rofecoxib could delay a diagnosis of AD in patients with mild cognitive impairment (MCI), a group with an expected annual AD diagnosis rate of 10-15%. MCI patients > or =65 years were randomized to rofecoxib 25 mg (N=725) or placebo (N=732) daily for up to 4 years. The primary end point was the percentage of patients with a clinical diagnosis of AD. The estimated annual AD diagnosis rate was lower than the anticipated 10-15%: 6.4% in the rofecoxib group vs 4.5% in the placebo group (rofecoxib : placebo hazard ratio=1.46 (95% CI: 1.09, 1.94), p=0.011). Analyses of secondary end points, including measures of cognition (eg the cognitive subscale of the AD Assessment Scale (ADAS-Cog)) and global function (eg the Clinical Dementia Rating (CDR)), did not demonstrate differences between treatment groups. There was also no consistent evidence that rofecoxib differed from placebo in post hoc analyses comparing ADAS-Cog and CDR-sum of boxes scores in overlapping subgroups of patients who had Mini Mental State Exam scores of 24-26 in the present MCI study and in a previous AD treatment study with a similar design. The results from this MCI study did not support the hypothesis that rofecoxib would delay a diagnosis of AD. In conjunction with the lack of effects observed in previous AD studies, the findings suggest that inhibition of COX-2 is not a useful therapeutic approach in AD.

Aged↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2006

Microarray analysis of gene regulation by oxygen, nitrate, nitrite, FNR, NarL and NarP during anaerobic growth of Escherichia coli: new insights into microbial physiology.

RNA was isolated from cultures of Escherichia coli strain MG1655 and derivatives defective in fnr, narXL, or narXL with narP, during aerobic growth, or anaerobic growth in the presence or absence of nitrate or nitrite, in non-repressing media in which both strain MG1655 and an fnr deletion mutant grew at similar rates. Glycerol was used as the non-repressing carbon source and both trimethylamine-N-oxide and fumarate were added as terminal electron acceptors. Microarray data supplemented with bioinformatic data revealed that the FNR (fumarate and nitrate reductase regulator) regulon includes at least 104, and possibly as many as 115, operons, 68 of which are activated and 36 are repressed during anaerobic growth. A total of 51 operons were directly or indirectly activated by NarL in response to nitrate; a further 41 operons were repressed. Four subgroups of genes implicated in management of reactive nitrogen compounds, NO and products of NO metabolism, were identified; they included proteins of previously unknown function. Global repression by the nitrate- and nitrite-responsive two-component system, NarQ-NarP, was shown for the first time. In contrast with the frdABCD, aspA and ansB operons that are repressed only by NarL, the dcuB-fumB operon was among 37 operons that are repressed by NarP.

Anaerobiosis↗

PubMed2002

[Value of Ginkgo biloba in treatment of Alzheimer dementia].

During the last decade, there has been an explosive growth of research concerning the extract of Ginkgo biloba termed Egb 761. In experimental studies, animal studies and clinical studies Ginkgo biloba has shown a similar pharmacological potency and clinical efficacy like synthetic defined drugs in the therapy of reduced cerebral performance. Ginkgo biloba special extract Egb 761 is a standardized and highly purified extract of Ginkgo leaves. Among the active constituents are the ginkgo-flavone glycosides and the terpene-lactones (ginkgolides, bilobalide). The multifactorial principle of action of Ginkgo biloba is characterized by rheological and blood-flow-promoting properties, protective effects against ischaemia and hypoxia, effects on nerve cell energy metabolism, antioedematous and myelin-protective effects, radical-scavenger activity, effects on various cerebral transmitter and receptor systems. These action principles constitute the rationale for clinical trials in vascular dementia and primary degenerative dementia of the Alzheimer type, and in mixed forms of both. The cerebral bioavailability of Ginkgo biloba extract has been demonstrated by electroencephalography. In clinical trials of different working-groups, effects of Ginkgo biloba on the cognitive performance, global function, and activities of the daily living have been found. Metaanalysis in the indication--demential disorders--comparing Ginkgo biloba versus acetylcholinesterase inhibitors have shown a similar clinical efficacy of both therapy regimens with an additional drug safety benefit for Ginkgo. Due to the clinical efficacy the WHO accepted Ginkgo biloba as an antidementiv drug and add it in January 2000 into the recent ATC-Classification Index. In future antidementive therapy drugs with an different mode of action should be given in combination. Furthermore clinical trials with fixed combinations of acetylcholinesterase inhibitors with Ginkgo biloba extracts in moderate or severe dementia would be necessary.

Aged↗

PubMedDate not supplied

Psychosocial correlates of suicidal intent among patients with schizophrenia.

Suicidal intent is common among patients with schizophrenia, resulting in extreme personal distress, increased hospitalizations and healthcare expenditures, and early mortality. However, the psychosocial correlates of current suicidality among schizophrenic patients are not fully understood. This study attempted to identify psychosocial correlates of current suicidal intent in a sample of 267 patients with schizophrenia. Multiple regression analyses were used to assess the relationship between suicidality and current symptomatology, psychosocial problems, global functioning, and demographic characteristics. Results showed that depressive symptomatology as a single variable accounted for approximately 50% of the variance in ratings of suicidal intent. In addition, female gender, younger age, recent traumatic stress, and less severe psychotic symptoms each significantly predicted current suicidality independent of depressive symptoms. The combination of depression among younger female schizophrenic patients whose psychotic symptoms have abated and who are experiencing current traumatic stress may indicate extreme suicidal intent.

Adolescent↗

PubMed2000

[Left ventricular heart volume determination with fast MRI in breath holding technique: how different are quantitative heart catheter, quantitative MRI and visual echocardiography?].

GOAL: Comparison of fast MRI, echocardiography (Echo), and ventricular angiography (Cath) in the assessment of left ventricular global function. METHODS: Fast MRI in short axis plane, biplane Cath, and 2D Echo were performed in 62 patients [35 coronary artery diseases, 16 acquired valvular diseases (VD), 9 dilated cardiomyopathies (DCM), 1 congenital heart disease and 1 heart transplantation]. Enddiastolic (EDV), endsystolic (ESV), stroke volumes (SV), cardiac output (CO), and ejection fraction (EF) were compared in MRI and Cath. EF was visually estimated in 2D Echo by an experienced observer. RESULTS: In comparison to MRI, Cath overestimated EF by 8.4%, and Echo underestimated EF by 5.6%. The limits of agreement between MRI and Cath in EF were +/- 23.8%, between MRI and Echo +/- 18%, and between Echo and Cath +/- 19.4%. Significant differences were found between Cath and MRI in EDV, SV, and CO, but not for ESV. The best agreement in EF was found in the group with DCM, the worst in the group with VD. CONCLUSION: Important systemic and random errors were found in the comparison of MRI, Echo, and Cath. For therapy decision and follow-up, the methods should not be exchanged unscrupulously.

Adult↗

PubMed2003

[Presentation and stability of cognitive and noncognitive symptom patterns in patients with Alzheimer's disease. Disease course over a two-year period under constant treatment conditions with rivastigmine].

The course of behavioural and psychotic features of patients with Alzheimer's disease treated with an inhibitor of the acetylcholinesterase (rivastigmine), and their association to cognitive impairment is presented in the study. Standardized examination of global functional deterioration (GDS), cognitive impairment (MMSE) and behavioural or psychotic symptoms (Behave-AD) were performed over two years. We could analyse the complete data from 44 of initially 91 patients with mild to moderate Alzheimer's disease. The cognitive component (measured by MMSE, ADAS-cog) and the functional assessment (GDS) showed a continuous decline after a one year period of stabilization, in contrast with behavioural and psychotic symptoms, especially delusions, which still improved after treatment of two years. While cognitive items in correlation with functional aspects formed a homogeneous factor over the two-year period, psychotic features displayed more variability over time evaluated by factor analysis. Nevertheless mood and anxiety disorder in combination with aggressive behaviour as well as hallucinations formed an independent factor in the course of Alzheimer's disease. In addition to other studies of the course of Alzheimer's disease we could demonstrate that distinct behavioural and psychotic symptoms may also present as independent factors in Alzheimer patients under constant treatment conditions with an inhibitor of the acetylcholinesterase (rivastigmine).

Affective Disorders, Psychotic↗

PubMed2003

Early detection and intervention in the initial prodromal phase of schizophrenia.

Attenuated and transient psychotic symptoms as well as a combination of different risk indicators and a recent significant deterioration in global functioning are currently used as a preliminary definition of the initial prodromal or at-risk mental state by the vast majority of investigators in research on early psychosis detection and intervention. Recently published results demonstrated a mean progression to frank psychosis within one year in 36.7 % of cases showing emerging symptoms, indicating that these criteria already seem to provide a satisfying assessment for risk of an imminent psychosis. However, as functional decline often sets in before this time, detection in earlier prodromal stages seems necessary. In a prospective study, certain basic cognitive and perceptive symptoms showed good to excellent predictive accuracy for schizophrenic psychosis, thus potentially offering a reasonable approach for earlier detection. Early intervention is aimed at improving prodromal symptoms, avoiding functional deterioration, and suppressing or delaying transition to psychosis. Initial study results targeting an earlier or later prodromal phase are promising, but longer follow-ups and larger samples are needed.

Disease Progression↗

PubMed2006

[Needs for care of former long-stay-patients living outside of the psychiatric hospital].

OBJECTIVE: The aim of this study was to assess the needs for care of 116 former long-stay patients during the first 42.9 months after discharge. METHOD: Patients and mental health professionals rated needs using the "Berliner Bedürfnisinventar" (Berlin Needs for Care Inventory). RESULTS: Out of a total of 16 needs areas, patients reported a mean number of 7.6 needs, therapists reported 10 needs. Patients with lower global functioning scores showed a significantly lower number of needs, while patients living in psychiatric nursing homes and patients with learning disabilities had a significantly higher number of needs. In most areas, agreement between patients' and therapists' assessment was good to moderate. In most areas the rate of unmet versus total needs was above 90 %. Patients received help almost exclusively from institutions or mental health services. CONCLUSION: The care needs of discharged patients were generally met and placement in institutions was considered appropriate.

Activities of Daily Living↗

PubMed1998

Long-term follow-up after finger and upper-limb replantation: clinical, angiologic, and lymphographic studies.

This 10-year follow-up study evaluates 25 patients with a total of 57 successfully replanted fingers and six successfully replanted upper limbs. The global functional loss, including loss of range of motion, sensibility, and strength of the hand, was determined using the "Millesi score." The hemodynamic parameters of replanted and control fingers under resting and stress conditions were measured using a laser Doppler flowmeter. The lymphatic system at the site of replantation was examined by fluorescence microlymphography. All patients showed a considerable functional loss, according to the Millesi score, that averaged 56 percent of the normal function of the hand. In order to overcome functional deficit, many patients had developed successful compensatory mechanisms. In general, the patients themselves subjectively rated their functional deficits lower than indicated by the Millesi score. Laser Doppler flowmetry at rest and after arterial occlusion, and capillaroscopy before, during, and after a cold provocation test, revealed subnormal resting flow conditions and significantly decreased vascular capacity in the replanted fingers. Lymphatic drainage capacity was also significantly reduced despite documented reanastomosis between the skin microlymphatic network distal and proximal to the scar (fluorescence microlymphography). The coexistence of functional loss with compensatory mechanisms, decreased reactive hyperemia, and deficit in lymphatic drainage, present in all patients, must be considered as definitive sequelae of the initial injury.

Adolescent↗

PubMedDate not supplied

[Congenital subluxation of the metacarpophalangeal joint of the thumb as the cause of writer's syndrome].

A 26-year-old male patient developed a writer's cramp syndrome, the underlying cause of which was shown to be a congenital subluxation of the first metacarpophalangeal joint. The clinical symptoms are presented, the indications for surgery reviewed and the operative technique in accordance with A.N. Witt described. Post-operatively, the pathological hypermobility of the first metacarpophalangeal joint has been eliminated, and global function of the hand has normalized.

Adult↗

PubMedDate not supplied

Relationship between contractile reserve, Tl-201 uptake, and collateral angiographic circulation in collateral-dependent myocardium: implications regarding the evaluation of myocardial viability.

BACKGROUND: The aim of this study was to compare collateral angiographic circulation (CC), thallium 201 single photon emission computed tomography (SPECT), low-dose dobutamine echocardiography (LDDE), and their combination in identifying viable myocardium beyond a chronic occlusion. METHODS AND RESULTS: We studied 33 consecutive patients with a chronic occluded coronary artery and regional ventricular dysfunction who underwent dobutamine infusion (5-10 microg x kg(-1) x min(-1)), Tl-201 SPECT, and coronary revascularization (15 patients underwent coronary artery bypass grafting and 18 patients percutaneous transluminal coronary angioplasty). Echocardiography and Tl-201 SPECT at rest were repeated 90 +/- 48 days after revascularization. For viability assessment, Tl-201 SPECT showed the best sensitivity and accuracy (77% and 72%, respectively) compared with LDDE (64% and 63%, respectively) and CC (74% and 55%, P < .05 vs Tl-201 SPECT). Specificity was significantly better for both Tl-201 SPECT (65%) and LDDE (62%) compared with collateral circulation (27%, P < .001 vs Tl-201 SPECT and LDDE). Furthermore, combined Tl-201 SPECT and LDDE data improved specificity (from 88% to 92%) and positive predictive power (from 75% to 78%) but not global accuracy. A direct relationship between the number of viable segments and global functional recovery after revascularization was found only in the case of Tl-201 SPECT (r = 0.48, P = .04). CONCLUSIONS: This study demonstrates that CC has a very low specificity in the evaluation of viability in collateral-dependent myocardium and that LDDE has a very low sensitivity, whereas Tl-201 SPECT is the most reliable method, particularly in akinetic segments, and optimally identifies patients who will mostly benefit from revascularization in terms of ventricular functional improvement. No additional advantages in terms of accuracy were found when Tl-201 SPECT and LDDE data were combined.

Aged↗

PubMed2002

Gene transfection of hepatocyte growth factor attenuates cardiac remodeling in the canine heart: A novel gene therapy for cardiomyopathy.

OBJECTIVE: Hepatocyte growth factor, a potent angiogenic agent, is unique in having the effects of antiapoptosis and antifibrosis. In the present study we used the rapid pacing-induced heart failure canine model to investigate the effect of gene transfection of hepatocyte growth factor on the failing heart. METHODS: Four weeks after onset of rapid pacing, either the human hepatocyte growth factor gene (160 microg; hepatocyte growth factor group, n = 7) or empty vector (control group, n = 7) was directly injected into the left ventricular myocardium by means of the hemagglutinating virus of Japan liposome method. RESULTS: At 4 weeks after gene transfection, the left ventricular global function, assessed by means of pressure-volume loop analysis, was improved in the hepatocyte growth factor group as preload-recruitable stroke work (percentage of baseline: 80% +/- 20% from 38% +/- 15% before gene transfection, P =.005), whereas it was not changed in the control group (50% +/- 18% from 50% +/- 18%). Weekly echocardiography showed that this improvement began in the week after gene transfer. The hearts in the hepatocyte growth factor group had a large wall thickness, large myocyte diameter, high capillary density, low fibrotic area fraction, and low density of apoptotic nuclei revealed by means of histologic analysis compared with that in the control group. Myocardial perfusion flow, assessed with color microspheres, was increased in the hepatocyte growth factor group (percentage of baseline: 79% +/- 16% from 48% +/- 14%, P =.010), whereas it was reduced in the control group (30% +/- 12% from 45% +/- 17%). CONCLUSIONS: Gene transfection of hepatocyte growth factor promoted angiogenesis, improved perfusion, decreased fibrosis and apoptosis, promoted recovery from myocyte atrophy, and thereby attenuated cardiac remodeling and improved myocardial function in the failing heart. It is a novel gene therapy for human heart failure.

Animals↗

PubMed1993

Models of cognitive deficit and statistical hypotheses: multiple sclerosis, an example.

The purpose of the current study was to describe four models of cognitive deficit and to outline the statistical hypotheses underlying each model. The four models of cognitive deficit were (a) specific deficit; (b) subgroup deficit; (c) a syndrome dissociation model; and (d) a global function dissociation model. Neuropsychological data are analyzed to examine each of these four models in a sample of mild Multiple Sclerosis (MS) patients. The results suggest that for these subjects and tests, the specific deficit model best fits the data. The results are reviewed initially in the context of MS. There follows a consideration of statistical caveats and finally, general applications of the proposed procedures.

Adult↗

PubMed2003

Toward an acoustic typology of motor speech disorders.

Acoustic methods have progressed to the point that an acoustic typology of the motor speech disorders can be constructed from a parameteric assessment of the speech subsystems (e.g., phonation, nasal resonance, vowel articulation, consonant articulation, intonation, and rhythm). The results of this analysis can be interpreted in respect to global functions in speech (e.g., voice quality, intelligibility, and prosody). This paper reviews studies showing that specific acoustic analyses have demonstrated or potential value toward the overall goal of constructing acoustic profiles of dysarthria and apraxia of speech. Several different acoustic measures are relevant to the study of the motor speech disorders, and these are increasingly supported by normative data and by guidelines for clinical application. Examples of these applications are discussed for a variety of specific neurologic diseases or perceptual types of disorder. Acoustic studies are useful in the study of motor speech disorders and recent progress points to a parametric analysis.

Humans↗

PubMed2001

Parasuicides without follow-up.

The aim of this project was to approach subjects who committed parasuicide but did not primarily receive or accept a recommendation for care through the regular routines after referral to a general hospital. Three hundred and twenty-nine consecutive parasuicides in 10- to 89-year-olds (162 men and 167 women) were studied. One hundred were subsequently hospitalized in the departments of psychiatry, 130 were followed up at outpatient facilities, and 96 left without any follow-up. A psychiatric liaison consultation was made in 57% of the total sample. The 96 subjects without follow-up were compared with the subjects who received follow-up. The sample was somewhat younger and included slightly more men. They were single in 54% and unemployed in 43% of the cases. According to the DSM-IV, 27% had a concurrent depression. According to the CAGE questions, 57% had indication of substance addiction. Fifty-four per cent had currently low global functioning, less than 50 points on the GAF. They had not been in contact with psychiatric care previously to the same extent as the others. About 34% of these who did not receive or rejected follow-up initially after a second approach agreed to follow-up when contacted by the project team, referring them to appropriate authorities such as social welfare offices, family counselling, or psychosocial staff within psychiatry or primary care. This may imply that the group delineated is at risk for eventual suicide and that the acceptance of follow-up should be interpreted as an indication that a substantial number needs help and can be successfully encountered by means of a case manager approach.

Adolescent↗