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Dichloroacetate enhances myocardial functional and metabolic recovery following global ischemia.

This study was undertaken to determine the effect of dichloroacetate (DCA) on myocardial functional and metabolic recovery following global ischemia. Sixteen isolated rabbit hearts were subjected to 120 minutes of mildly hypothermic (34 degrees C) cardioplegic arrest with multi-dose, modified St. Thomas' cardioplegia. Following ischemia, hearts were reperfused with either a physiologic salt solution (PSS) as controls, (CON, N = 10), or PSS containing DCA (DCA, N = 6) at a concentration of 1 mmol/L. Functional and metabolic indices were determined at baseline and at 15, 30, and 45 minutes of reperfusion. Results were analyzed using analysis of variance (ANOVA, Sheffe F test) and significance was defined as P < 0.05. Functional recovery was significantly better in hearts reperfused with DCA. Developed pressure (DP) recovered to 62 +/- 4% of baseline in DCA hearts, compared to 37 +/- 8% in CON hearts. Recovery of dP/dt was also improved in DCA versus CON hearts (67 +/- 5 v 43 +/- 10%). Coronary blood flow was not different between groups either at baseline or during reperfusion, but myocardial oxygen consumption (MVO2) was increased in the DCA versus CON hearts (71 +/- 10% of baseline, v 51 +/- 19%). Diastolic compliance during reperfusion was improved in those hearts receiving DCA, as was myocardial mechanical use efficiency (DP/MVO2). Correction of myocardial tissue pH to baseline values was similar in both groups, indicating that the beneficial effect on functional recovery seen with DCA was not solely related to amelioration of acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Kidney function after radical nephrectomy: assessment by quantitative SPECT of 99mTc-DMSA uptake by the kidneys.

UNLABELLED: To determine the function of the remaining contralateral kidney after the removal of a functioning kidney, 30 consecutive patients (18 men, 12 women; average age, 67 y; age range, 34-87 y) who were undergoing unilateral radical nephrectomy were evaluated by sequential quantitative 99mTc-dimercaptosuccinic acid (DMSA) SPECT (QDMSA) studies. METHODS: The 30 patients were undergoing radical nephrectomy for renal tumors. The first study was done before surgery. Follow-up studies were performed 2-23 mo after surgery. Clinical evaluations and determinations of serum creatinine level were performed at the same time as the QDMSA studies. RESULTS: The relative contribution of the resected kidneys to the global renal function before surgery was 43.2% +/- 7.3%. After surgery the uptake of the remaining kidney increased from 13.4% +/- 4.0% to 18.3% +/- 5.8% (t = 5.7; P = 0.0000). The relative function of the remaining kidney increased from 56.8% +/- 7.1% to 79.1% +/- 23.6% (t = 4.9; P < 0.0001) of the global renal function before nephrectomy. Increases in the renal volume (from 211 +/- 62 cm3 to 229 +/- 68 cm3; t = 4.5; P = 0.0001) and in the percentage injected dose per cubic centimeter (%ID/cm3) of the remaining kidney (from 0.066 +/- 0.02 % ID/cm3 to 0.085 +/- 0.03 %ID/cm3; t = 4.6; P = 0.0001) were associated with this change. Nine patients had 2 follow-up studies performed 3-4 mo after surgery and 12-14 mo after surgery. The volume of the remaining kidney (209.22 +/- 46.20 cm3 versus 217.88 +/- 58.85 cm3; t = 0.962; P = 0.364), the %ID/cm3 (0.09 +/- 0.016 %ID/cm3 versus 0.093 +/- 0.025 %ID/cm3; t = 0.362; P = 0.726), and the percentage uptake (19.26% +/- 4.45% versus 20.11% +/- 7.01%) did not change significantly between these 2 QDMSA studies. CONCLUSION: The results of this study suggest that adaptive changes causing hyperfunction of the remaining kidney may occur after nephrectomy of a functioning kidney in adults. These changes occur soon after surgery, persist for at least 1 y, and are evident on QDMSA studies.

Adaptation, Physiological↗

Validation of a new automated method for analysis of gated-SPECT images.

We recently presented a new method for quantification of CArdiac FUnction--denoted CAFU--as the first step in the development of an automated method for integrated interpretation of gated myocardial perfusion single photon emission computed tomography (SPECT) images. The aim of this study was to validate CAFU in the assessment of global and regional function of the left ventricle. Quantitative gated-SPECT (QGS), the most widely used software package for quantification of gated-SPECT images, was used as reference method for the measurements of ejection fraction (EF) and ventricular volumes, and visual analysis by an experienced physician was used as reference method for the measurements of regional wall motion and thickening. Two different groups of consecutive patients referred for myocardial perfusion scintigraphy were studied. Global function was evaluated in 316 patients and regional function in 49 other patients. The studies were performed using a 2-day stress/rest 99 m-Tc-sestamibi protocol. A good correlation was found between EF values from QGS and CAFU (EF CAFU = 0.84 EF QGS + 13, r = 0.94), but CAFU values were on average 4 EF points higher than QGS values. With CAFU the segments with normal thickening according to the physician showed significantly higher thickening values (in all parts of the myocardium) compared to the segments classified as having abnormal thickening. In conclusion, this study demonstrates that CAFU can be used to quantify global and regional function in gated-SPECT images. This is an important step in our development of an automated method for integrated interpretation of gated-SPECT myocardial perfusion scintigraphy studies.

Adenosine↗

Protective effects of oral antioxidants on skin and eye function.

BACKGROUND: Antioxidants applied topically and/or taken systemically may play an important role in counteracting the oxidative injury to lipids and proteins on the skin and eye that are provoked by radical oxygen species. OBJECTIVE: The aim of the study was to control photoprotective activity of the skin and eye through the use of oral antioxidants in 50 smoker volunteers (10 cigarettes/d) aged between 25-36 years and affected by dry skin. METHODS: Oxidative stress was assessed by a randomized double-blind study, and the ROS-Meter System (Dermotech, Rome, Italy). Global visual function was determined by the use of different visual surveillance tests. RESULTS: A 40% decrease of oxidative stress in blood serum was verified, with a clear relationship between global visual function and the oral intake of an oxygenated carotenoid (lutein). CONCLUSIONS: Carotenoids used as nutritional supplements seem to play an interesting photoprotective role for both skin and eyes, eventually increasing the activity of topical sunscreens.

Administration, Oral↗

Early restoration of cardiac function in hearts with acute regional ischaemia. The importance of beta-adrenergic stimulation.

The effects of acute coronary artery occlusion in anaesthetized cats has been studied with regard to changes in cardiac function and regional myocardial blood flow. Occlusion of the left anterior decending coronary artery (LAD) is followed by a rapid reduction of peak systolic blood pressure (LVSP) and contractility (dP/dt) and increased left ventricular end-diastolic pressure (LVEDP). Five minutes after coronary occlusion heart rate, LVSP, and (dP/dt) was reduced and LVEDP increased. Global cardiac function measured by these variables was gradually restored to preocclusion values; LVSP after 10 min., heart rate and dP/dt after 20 min. After 40 and 60 min these variables were stable at preocclusion levels. LVEDP remained permanently elevated. In hearts with regional ischaemia and paced heart rate global cardiac function was mainly restored 20 min after coronary occlusion except for increased LVEDP, both in cats pretreated with non-selective beta-adrenergic blockade (propranolol) and in unblocked cats. In general, blood flow in non-ischaemic myocardium adjacent to the ischaemic region increased following coronary occlusion, although not significantly in the endocardium. The endocardial/epicardial blood flow ratio was stable in unblocked hearts and was reduced in beta-blocked hearts. In normally perfused myocardium remote from the ischaemic region, blood flow increased following occlusion both in beta-blocked and unblocked cats, most pronounced in the epicardium; the endo/epicardial blood flow ratio decreased.

Adaptation, Physiological↗

Evoked potentials in severe brain injury.

Three-modality evoked potentials (EPs) have been used for several years in association with the electroencephalogram (EEG) as a diagnostic and prognostic tool in acute traumatic or nontraumatic coma. In 1993 we proposed to combine these in two indices: the index of global cortical function (IGCF) and the index of brain-stem conduction (IBSC). Four EP patterns based on both indices emerge at the acute stage of severe head trauma. These are easily explainable by pathophysiology. Pattern 1 corresponds to alterations in the index of global cortical function without changes in the index of brain-stem conduction. Its prognosis is good (80 to 90% of these patients recover). Pattern 2 is characterized by alterations of somatosensory EPs that are suggestive of midbrain dysfunction. The prognosis depends both on the reversibility of the midbrain dysfunction and on the extent of associated diffuse axonal lesions, whose evaluation requires MRI. Patients who recovered from Pattern 2 sometimes did so after a long interval during which they remained vegetative. Pattern 3 is characterized by alterations of brain-stem auditory EPs that are suggestive of pontine involvement. It usually follows uncontrolled intracranial hypertension and corresponds to evolving transtentorial herniation. All patients with that transient pattern eventually died. Pattern 4 is categorized by the disappearance of all activities of intracranial origin, contrasting with the preservation of all activities of retinal, spinal-cord, and peripheral-nerve origin. This pattern corresponds to brain death. In our experience, three-modality EPs are currently the best bedside brain-death confirmatory tool.

Brain↗

Transplantation of cryopreserved muscle cells in dilated cardiomyopathy: effects on left ventricular geometry and function.

OBJECTIVE: Cell transplantation to prevent congestive heart failure in patients with inherited dilated cardiomyopathy might require the use of noncardiac donor cells unaffected by the genetic defect and cryopreservation to permit cell storage until the time of transplantation. However, the effects of cryopreservation on peripheral muscle cells harvested from a cardiomyopathic recipient and their subsequent ability to restore cardiac structure and function after transplantation are unknown. METHODS: Skeletal myoblasts and vascular smooth muscle cells from cardiomyopathic hamsters (delta-sarcoglycan-deficient BIO 53.58 hamster) and age-matched normal donor hamsters were isolated, expanded in culture, and cryopreserved. After reanimation in culture, cell morphology and growth rate were assessed and compared with values seen in noncryopreserved cells. A total of 4 x 10(6) previously cryopreserved skeletal myoblasts (n = 10) and vascular smooth muscle cells (n = 10) harvested from cardiomyopathic donors were then transplanted into the left ventricles of 17-week-old BIO 53.58 hamsters. Hearts injected with culture medium alone (n = 11) served as controls. Heart function was assessed 5 weeks after transplantation on a Langendorff apparatus, and left ventricular geometry was quantified by means of computerized planimetry. Staining with 5-bromo-2'-deoxyuridine identified the injected cells. RESULTS: Vascular smooth muscle cells from cardiomyopathic donors had an abnormal morphology and diminished growth rates in culture compared with vascular smooth muscle cells from normal donors. These markers of injury were exacerbated by cryopreservation. In contrast, vascular smooth muscle cells from normal donors and skeletal myoblasts from either cardiomyopathic or normal donors appeared normal in culture and were unaffected by cryopreservation. Both cryopreserved vascular smooth muscle cells and skeletal myoblasts from cardiomyopathic donors formed a viable muscle-resembling tissue that prevented wall thinning, limited left ventricular dilatation, and preserved global systolic function in hamsters with a genetic dilated cardiomyopathy. However, attenuation of cardiac remodeling and preservation of global heart function was greater after skeletal myoblast transplantation compared with vascular smooth muscle cell transplantation in parallel to the in vitro morphologic and growth characteristics of these cells. CONCLUSIONS: Cryostorage of healthy donor cells does not prevent the benefits of cell transplantation on limiting remodeling and preserving cardiac function in the failing heart. The health of donor cells in vitro predicts their subsequent benefits on cardiac structure and function after transplantation. Cryopreservation of donor cells might facilitate a clinically applicable and effective approach for ventricular restoration with cell-transplantation therapy for patients with inherited dilated cardiomyopathy.

Analysis of Variance↗

Functional genomic analysis of global regulator NolR in Sinorhizobium meliloti.

NolR is a regulator of nodulation genes present in species belonging to the genera Rhizobium and Sinorhizobium. The expression of the nolR gene in Sinorhizobium meliloti AK631 was investigated in relation to stage of growth, availability of nutrients, and different environmental stimuli using the nolR::lacZ fusion report system. It has been shown that the nolR gene is regulated in a population-density-dependent fashion and influenced by a number of environmental stimuli, including nutrients, pH, and oxygen. Exploration of the physiological functions of NolR under various laboratory conditions has shown that NolR is required for the optimal growth of the bacteria on solid media, optimal survival of the bacteria in carbon-starved minimal medium, and after heat shock challenge. NolR also is involved in recipient-induced conjugative transfer of a plasmid. Proteome analysis of strain AK631 and its Tn5-induced nolR-deficient mutant EK698 revealed that a functional NolR induced significant differences in the accumulation of 20 polypeptides in peptide mass fingerprinting early-log-phase cultures and 48 polypeptides in stationary-phase cultures. NolR acted mainly as a repressor in the early-log-phase cultures, whereas it acted as both repressor and activator in the stationary-phase cultures. The NolR protein and 59 NolR-associated proteins have been identified by peptide mass fingerprinting. The NolR protein was differentially expressed only in the NolR+ wild-type strain AK631 but not in its NolR- derivative EK698, confirming that no functional NolR was produced in the mutant. The NolR-associated proteins have diverse functions in amino acid metabolism, carbohydrate metabolism, lipid metabolism, nucleotide metabolism, energy metabolism, metabolism of Co-factors, and cellular adaptation and transportation. These results further support our previous proposal that the NolR is a global regulatory protein which is required for the optimization of nodulation, bacterial growth and survival, and conjugative transfer of a plasmid.

Bacterial Proteins↗

Phase II study of alpha-tocopherol in improving the cognitive function of patients with temporal lobe radionecrosis.

BACKGROUND: Radiotherapy is an important treatment modality for brain tumors and is the standard radical treatment for nasopharyngeal carcinoma (NPC). However, the treatment is not free of side effects, and one possible neurologic sequela is the occurrence of temporal lobe radionecrosis (TLN) associated with cognitive dysfunction. Currently, there is no effective intervention to improve patients' cognitive performance. METHODS: Twenty-nine patients with TLN after radiotherapy for NPC were recruited on a voluntary basis. Among them, 19 patients (15 males and 4 females) received a megadose of alpha-tocopherol (vitamin E) (2000 international units per day) for 1 year, whereas the other 10 (5 males and 5 females) served as control patients. Their cognitive function (i.e., global cognitive ability, attention, memory, language, and executive function) was evaluated by a battery of neuropsychological tests before and after treatment. RESULTS: Significant improvement in global cognitive ability (P = 0.035) and memory (verbal: P = 0.036; visual: P = 0.007) occurred among patients in the treatment group after a 1-year medication period. In addition, the executive function of the treatment group improved significantly (P = 0.04). No difference was found between the two groups with respect to attention or language. CONCLUSIONS: The current investigation was a preliminary study on the effect of alpha-tocopherol on the cognitive function of patients with TLN after radiotherapy for NPC. In view of the absence of effective treatment for patients with cerebral radionecrosis, alpha-tocopherol has the potential to be a complementary intervention for patients with cognitive dysfunction due to TLN.

Aged↗

Alterations of systolic left ventricular twist after acute myocardial infarction.

We sought to characterize the alterations of left ventricular (LV) twist after acute myocardial infarction in humans and to study their relationship to usual parameters of LV function. Systolic LV twist was measured by color tissue Doppler echocardiography (TDE) in 34 patients after anterior myocardial infarction and in 20 controls. In a subset of controls and patients, the assessment of LV twist by TDE was validated against magnetic resonance (MR) tissue tagging with good agreement between the two methods. Myocardial ischemia was responsible for a decrease in LV twist in infarct patients (P < 0.01). The decrease in LV twist was correlated with the extent of the asynergic area and global LV function as assessed by LV cineangiography (P < 0.001). Thus acute myocardial ischemia is responsible for a decrease in LV twist that is related to global LV function. Color TDE is a promising technique for straightforward assessment of LV twist in humans.

Acute Disease↗

[Evaluation of hepatic function by hepatobiliary scintigraphy using factor analysis].

Factor analysis of hepatobiliary scintigraphy using 99mTc-N-pyridoxyl-5-methyltryptophan (99mTc-PMT) was performed, and functional factor of liver parenchyma (FA-hepatogram) was obtained. Two parameters (peak time, T 1/2) were calculated from this hepatogram. A good correlation was obtained between these parameters and ICG-R15; furthermore, these parameters were prolonged in patients with normal volunteers, chronic hepatitis, compensated and decompensated liver cirrhosis in this order. Conventional hepatogram by ROI method (ROI-hepatogram) was not suitable for the evaluation of global liver function in condition such as a large intrahepatic mass, intrahepatic gall bladder, dilatation of biliary tree, and severe liver cirrhosis. But, even in such cases, FA-hepatogram was useful for the evaluation of global liver function.

Biliary Tract↗

Left ventricular concentric remodeling is associated with decreased global and regional systolic function: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The transition from compensatory concentric remodeling to myocardial failure is not completely understood in humans. To investigate determinants of incipient myocardial dysfunction, we examined the association between concentric remodeling and regional LV function in asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: Myocardial tagged MRI was performed. Regional myocardial function expressed as peak systolic midwall circumferential strain (Ecc) was analyzed in 441 consecutive studies by HARP (Harmonic Phase) tool. Peak Ecc was correlated with the extent of concentric remodeling determined by the ratio of left ventricular mass to end-diastolic volume (M/V ratio). In men, a gradual decline in peak global Ecc was seen with increasing M/V ratio (test for trend, P<0.001). Among women, however, Ecc tended to be lower only in the fifth compared with the first quintile of M/V ratio (P=0.1). The association of lower Ecc with increasing M/V ratio was regionally heterogeneous but was particularly prominent in the LAD region in men (test for trend, P<0.001) and in women (test for trend, P=0.02). In the right coronary and left circumflex artery territories, these associations were less marked in both genders. CONCLUSIONS: In this cross-sectional study of asymptomatic individuals, concentric left ventricular remodeling was related to decreased regional systolic function. The reduction in regional function, which was more pronounced in the left anterior descending coronary artery territory, may reflect the local transition from compensatory remodeling to myocardial dysfunction.

Atherosclerosis↗

Superiority of magnesium cardioplegia in neonatal myocardial protection.

BACKGROUND: We have shown that magnesium can offset the detrimental effects of normocalcemic cardioplegia in hypoxic neonatal hearts. It is not known, however, whether magnesium offers any additional benefit when used in conjunction with hypocalcemic cardioplegia. METHODS: Twenty neonatal piglets underwent 60 minutes of ventilator hypoxia (FiO2 8% to 10%) followed by 20 minutes of normothermic ischemia on cardiopulmonary bypass (hypoxic-ischemic stress). They then underwent 70 minutes of multidose blood cardioplegic arrest. Five (Group 1), received a hypocalcemic (Ca+2 0.2 to 0.4 mM/L) cardiologic solution without magnesium, whereas in 10, magnesium was added at either a low dose (5 to 6 mEq/L, Group 2) or high dose (10 to 12 mEq/L, Group 3). In the last 5 (Group 4), magnesium (10 to 12 mEq/L) was added to a normocalcemic cardioplegic solution. Function was assessed using pressure volume loops and expressed as percentage of control. RESULTS: Compared to hypocalcemia cardioplegic solution without magnesium (Group 1), both high- and low-dose magnesium enrichment (Groups 2 and 3) improved myocardial protection resulting in complete return of systolic (40% vs 101% vs 102%) (p < 0.001 vs Groups 2 and 3) and global myocardial function (39% vs 102% vs 101%) (p < 0.001 vs Groups 2 and 3), and reduced diastolic stiffness (267% vs 158% vs 154%) (p < 0.001 vs Groups 2 and 3). Conversely, even high-dose magnesium supplementation could not offset the detrimental effects of normocalcemic cardioplegia resulting in depressed systolic (End Systolic Elastance [EES] 41%+/-1%) (p < 0.001 vs Groups 2 and 3) and global myocardial function (40%+/-1%) (p < 0.001 vs Groups 2 and 3), and a marked rise in diastolic stiffness (258%+/-5%) (p < 0.001 vs Groups 2 and 3). Hypocalcemic magnesium cardioplegia has now been used successfully in 247 adult and pediatric patients. CONCLUSIONS: Magnesium enrichment of hypocalcemic cardioplegic solutions improves myocardial protection resulting in complete functional preservation. However, magnesium cannot prevent the detrimental effects of normocalcemic cardioplegia when the heart is severely stressed. This study, therefore, strongly supports using both a hypocalcemic cardioplegic solution and magnesium supplementation as their benefits are additive.

Adenosine Diphosphate↗

Acute changes of global and regional left ventricular function immediately after direct myocardial revascularization.

Direct myocardial revascularization (DMR) has been proposed to treat patients with severe coronary artery disease who are not amenable for classical revascularization techniques such as percutaneous coronary intervention (PCI) or bypass surgery (CABG). Although recent reports suggest its benefit in alleviating patients' complaints in the long term, there is still a paucity of data on the immediate impact on regional and global myocardial functioning following this treatment. In this overview we discuss our own experience and provide a summary of other data currently available.

Coronary Disease↗

Measuring the epidemiology of distress: the rheumatology distress index.

OBJECTIVES: (1) To examine clinical and psychological variables to determine which are associated with psychologic and psychosocial severity or "distress"; (2) to investigate whether patients with the 2 major rheumatic disorders, rheumatoid arthritis (RA) and osteoarthritis (OA), differ in distress variables and distress; and (3) to develop and validate a simple, clinically acceptable index of distress suitable for routine care and research purposes. METHODS: A total of 2,403 patients were evaluated in 2 data sets (N = 1,399 and N = 1,490). The first data set was evaluated in the clinic by a routine clinical examination and administration of the Clinical Health Assessment Questionnaire (CLINHAQ). This instrument includes measures of pain, global severity, functional disability, anxiety, depression, sleep disturbance, fatigue, health satisfaction, and health status. The second data set was evaluated by a mailed questionnaire that included the CLINHAQ, but also coping scales, the Beliefs in Pain Control Questionnaire, the Self Performance Scale, and the Arthritis Helplessness Index. RESULTS: RA and OA groups had similar scores for the variables associated with distress: pain, global severity, functional disability, anxiety, depression, sleep disturbance, fatigue, health satisfaction, and health status. Patients with fibromyalgia (FM) had more abnormal scores for every variable, reflecting overall distress. Using patients with FM as a "gold standard" of distress, we developed an index in data set 2. the Rheumatology Distress Index (RDI), made up of 5 variables, anxiety, depression, global severity, fatigue, and sleep disturbance, that best identified patients with FM compared to other patients. We then validated the instrument on the distress severity clusters formed in data set 1. The correlation between RDI and distress severity cluster was 0.874 with all patients considered and 0.867 with FM patients excluded. In addition, RDI predicted 1,174 of 1,399 (83.9%) cluster memberships correctly. Compared with a battery of psychological and clinical tests that classified 74% of FM and non-FM patients correctly, the RDI and is only slightly less effective, classifying 70.3% correctly. CONCLUSION: Distress is a patient rather than a disease phenomenon. A simple, easy to administer self-report questionnaire can be used to classify patients according to their level of distress. The resulting index, the RDI. accurately identifies distressed and non-distressed patients. Such an index should be useful for patient care and research.

Aged↗

Mismatch negativity deficits are associated with poor functioning in schizophrenia patients.

BACKGROUND: Schizophrenia patients exhibit widespread deficits in many domains, ranging from abnormalities in preattentional sensory processing to gross impairments in everyday functioning. Mismatch negativity (MMN) is an event-related potential measure that occurs in the absence of directed attention. While many studies have reported MMN deficits in schizophrenia patients, little is known about the functional significance of MMN deficits in schizophrenia patients. OBJECTIVE: To determine if a schizophrenia-linked deficit in MMN, an "automatic" preattentional measure, is associated with impairments in everyday functional status, level of independence in living situation, and the ability to perform tasks routinely encountered in everyday situations. SETTING AND PARTICIPANTS: Twenty-five patients with a DSM-IV diagnosis of schizophrenia recruited from inpatient and outpatient community facilities affiliated with the University of California, San Diego, and 25 healthy, nonpsychiatric, comparison subjects. MAIN OUTCOME MEASURES: Mismatch negativity, clinical symptoms, performance on a multidimensional laboratory-based functional skills assessment battery, clinician ratings on the Global Assessment of Functioning Scale, and level of independence in community living situation. RESULTS: Schizophrenia patients had significantly reduced MMN (P<.001). Greater levels of MMN impairment were associated with lower Global Assessment of Functioning Scale ratings. Consistent with clinical ratings, patients with greater MMN impairments were more likely to live in highly structured vs independent settings. A regional analysis of MMN revealed that the largest correlations of MMN to everyday functioning were present at frontocentral recording sites (eg, r(s) = -0.65). In contrast, MMN deficits were not associated with symptom severity or performance on laboratory-based tasks measuring skills that are often considered necessary for independent living. CONCLUSIONS: This pattern of results suggests that MMN deficits represent a core neurophysiological dysfunction that is linked to global impairments in everyday functioning in schizophrenia patients. These deficits in automatic preattentive information processing account for up to 42% of the variance in global functional status in schizophrenia patients. Thus, basic preattentional cognitive deficits may be excellent measures for predicting functional outcome. Longitudinal studies are needed to better understand the relationships between deficits in automatic sensory information processing, associated neural substrate dysfunctions, and deficits in everyday functioning across the course of the illness.

Activities of Daily Living↗

Revising polypharmacy to a single antipsychotic regimen for patients with chronic schizophrenia.

Antipsychotic polypharmacy has been empirically used and a recent trend in favour of that mode of therapy has been suggested for the treatment of schizophrenia. The clinical efficacy, however, still remains to be clarified. In order to critically evaluate the usefulness of such kind of psychopharmacotherapy, antipsychotic combination regimen (polypharmacy) was switched to a treatment with the single main antipsychotic (monotherapy) in cross-tapered fashion, while approximately maintaining the total amount, for patients with chronic schizophrenia. Patients had been treated with an average of three antipsychotics and maintained with the same antipsychotic polypharmacy regimen for more than 6 months before the entry. They were followed up with an antipsychotic monopharmacy and evaluated at 24 wk after completion of switching. Forty-seven patients were recruited for this study. Of 44 patients for whom evaluation was possible, 24 (54.5%) remained stable, while 10 (22.7%) showed improvement and the same number of patients ended in a deleterious status. Twenty-two patients were converted to antipsychotic monotherapy, while another 12 needed minimal dosing of low-potency agents. Overall, social functioning, evaluated by the Global Assessment of Functioning and the Clinical Global Impression, remained unchanged. Eighteen of 34 successful patients showed adverse effects of the main antipsychotic medication, which necessitated a significant dose reduction. Nine out of 10 deteriorating patients had been treated with a combination of low- and high-potency antipsychotics. It is suggested that many instances of antipsychotic polypharmacy is avoidable. The result is compatible with the current treatment recommendations, which dictate the use of a single antipsychotic agent.

Adult↗

[Proposal for a global medico-legal functional evaluation of disabilities of the hand].

The present evaluations of hand invalidity are based on parameters that can give correct assessment for amputations or for single stiffness, but these parameters are not able to evaluate the majority of lesions. A nerve lesion does not repair at 100% or at 0%; all degrees are possible. The same is true for vascular, tendon and muscular lesions. We studied a new global evaluation on a large number of patients and we compared it with the tables in use today. The assessed parameters are: the active and passive movement, ability of the hand, strength, duration of the effort or of the fatigue, trophism, sensibility, pain, aesthetics.

Disability Evaluation↗