Reductions in C-reactive protein in older adults with type 2 diabetes are related to improvements in body composition following a randomized controlled trial of resistance training.

BACKGROUND: Reductions in skeletal muscle mass and increased adiposity are key elements in the aging process and in the pathophysiology of several chronic diseases. Systemic low grade inflammation associated with obesity has been shown to accelerate the age-related decline in skeletal muscle. The aim of this investigation was to determine the effects of 12 months of progressive resistance training (PRT) on systemic inflammation, and whether reductions in systemic inflammation were associated with changes in body composition. We hypothesized that reductions in systemic inflammation following 12 months of PRT in older adults with type 2 diabetes would be associated with reductions in adiposity and increases in skeletal muscle mass. METHODS: Participants (n = 103) were randomized to receive either PRT or sham-exercise, 3 days a week for 12 months. C-reactive protein (CRP) was used to assess systemic inflammation. Skeletal muscle mass and total fat mass were determined using bioelectrical impedance. RESULTS: Twelve months of PRT tended to reduce CRP compared to sham exercise (ß = -0.25, p = 0.087). Using linear mixed-effects models, the hypothesized relationships between body composition adaptations and CRP changes were significantly stronger for skeletal muscle mass (p = 0.04) and tended to be stronger for total fat mass (p = 0.07) following PRT when compared to sham-exercise. Using univariate regression models, stratified by group allocation, reductions in CRP were associated with increases in skeletal muscle mass (p = 0.01) and reductions in total fat mass (p = 0.02) in the PRT group, but not in the sham-exercise group (p = 0.87 and p = 0.32, respectively). CONCLUSIONS: We have shown for the first time that reductions in systemic inflammation in older adults with type 2 diabetes following PRT were associated with increases in skeletal muscle mass. Furthermore, reductions in CRP were associated with reductions in adiposity, but only when associated with PRT. Lifestyle interventions aimed at reducing systemic inflammation in older adults with type 2 diabetes should therefore incorporate anabolic exercise such as PRT to optimize the anti-inflammatory benefits of favorable body composition adaptations.

Effects of high-intensity progressive resistance training and targeted multidisciplinary treatment of frailty on mortality and nursing home admissions after hip fracture: a randomized controlled trial.

RATIONALE: Excess mortality and residual disability are common after hip fracture. HYPOTHESIS: Twelve months of high-intensity weight-lifting exercise and targeted multidisciplinary interventions will result in lower mortality, nursing home admissions, and disability compared with usual care after hip fracture. DESIGN: Randomized, controlled, parallel-group superiority study. SETTING: Outpatient clinic PARTICIPANTS: Patients (n = 124) admitted to public hospital for surgical repair of hip fracture between 2003 and 2007. INTERVENTION: Twelve months of geriatrician-supervised high-intensity weight-lifting exercise and targeted treatment of balance, osteoporosis, nutrition, vitamin D/calcium, depression, cognition, vision, home safety, polypharmacy, hip protectors, self-efficacy, and social support. OUTCOMES: Functional independence: mortality, nursing home admissions, basic and instrumental activities of daily living (ADLs/IADLs), and assistive device utilization. RESULTS: Risk of death was reduced by 81% (age-adjusted OR [95% CI] = 0.19 [0.04-0.91]; P < .04) in the HIPFIT group (n = 4) compared with usual care controls (n = 8). Nursing home admissions were reduced by 84% (age-adjusted OR [95% CI] = 0.16 [0.04-0.64]; P < .01) in the experimental group (n = 5) compared with controls (n = 12). Basic ADLs declined less (P < .0001) and assistive device use was significantly lower at 12 months (P = .02) in the intervention group compared with controls. The targeted improvements in upper body strength, nutrition, depressive symptoms, vision, balance, cognition, self-efficacy, and habitual activity level were all related to ADL improvements (P < .0001-.02), and improvements in basic ADLs, vision, and walking endurance were associated with reduced nursing home use (P < .0001-.05). CONCLUSION: The HIPFIT intervention reduced mortality, nursing home admissions, and ADL dependency compared with usual care.

Study of Mental Activity and Regular Training (SMART) in at risk individuals: a randomised double blind, sham controlled, longitudinal trial.

BACKGROUND: The extent to which mental and physical exercise may slow cognitive decline in adults with early signs of cognitive impairment is unknown. This article provides the rationale and methodology of the first trial to investigate the isolated and combined effects of cognitive training (CT) and progressive resistance training (PRT) on general cognitive function and functional independence in older adults with early cognitive impairment: Study of Mental and Regular Training (SMART). Our secondary aim is to quantify the differential adaptations to these interventions in terms of brain morphology and function, cardiovascular and metabolic function, exercise capacity, psychological state and body composition, to identify the potential mechanisms of benefit and broader health status effects. METHODS: SMART is a double-blind randomized, double sham-controlled trial. One hundred and thirty-two community-dwelling volunteers will be recruited. Primary inclusion criteria are: at risk for cognitive decline as defined by neuropsychology assessment, low physical activity levels, stable disease, and age over 55 years. The two active interventions are computerized CT and whole body, high intensity PRT. The two sham interventions are educational videos and seated calisthenics. Participants are randomized into 1 of 4 supervised training groups (2 d/wk×6 mo) in a fully factorial design. Primary outcomes measured at baseline, 6, and 18 months are the Alzheimer's Disease Assessment Scale (ADAS-Cog), neuropsychological test scores, and Bayer Informant Instrumental Activities of Daily Living (B-IADLs). Secondary outcomes are psychological well-being, quality of life, cardiovascular and musculoskeletal function, body composition, insulin resistance, systemic inflammation and anabolic/neurotrophic hormones, and brain morphology and function via Magnetic Resonance Imaging (MRI) and Spectroscopy (fMRS). DISCUSSION: SMART will provide a novel evaluation of the immediate and long term benefits of CT, PRT, and combined CT and PRT on global cognitive function and brain morphology, as well as potential underlying mechanisms of adaptation in older adults at risk of further cognitive decline. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ANZCTRN12608000489392.

Recurrent and injurious falls in the year following hip fracture: a prospective study of incidence and risk factors from the Sarcopenia and Hip Fracture study.

BACKGROUND: The incidence and etiology of falls in patients following hip fracture remains poorly understood. METHODS: We prospectively investigated the incidence of, and risk factors for, recurrent and injurious falls in community-dwelling persons admitted for surgical repair of minimal-trauma hip fracture. Fall surveillance methods included phone calls, medical records, and fall calendars. Potential predictors of falls included health status, quality of life, nutritional status, body composition, muscle strength, range of motion, gait velocity, balance, walking endurance, disability, cognition, depression, fear of falling, self-efficacy, social support, physical activity level, and vision. RESULTS: 193 participants enrolled in the study (81 +/- 8 years, 72% women, gait velocity 0.3 +/- 0.2 m/s). We identified 227 falls in the year after hip fracture for the 178 participants with fall surveillance data. Fifty-six percent of participants fell at least once, 28% had recurrent falls, 30% were injured, 12% sustained a new fracture, and 5% sustained a new hip fracture. Age-adjusted risk factors for recurrent and injurious falls included lower strength, balance, range of motion, physical activity level, quality of life, depth perception, vitamin D, and nutritional status, and greater polypharmacy, comorbidity, and disability. Multivariate analyses identified older age, congestive heart failure, poorer quality of life, and nutritional status as independent risk factors for recurrent and injurious falls. CONCLUSIONS: Recurrent and injurious falls are common after hip fracture and are associated with multiple risk factors, many of which are treatable. Interventions should therefore be tailored to alleviating or reversing any nutritional, physiological, and psychosocial risk factors of individual patients.

Methodology and baseline characteristics for the Sarcopenia and Hip Fracture study: a 5-year prospective study.

BACKGROUND: Age-related hip fractures are associated with poor functional outcomes, resulting in substantial personal and societal burden. There is a need to better identify reversible etiologic predictors of suboptimal functional recovery in this group. METHODS: The Sarcopenia and Hip Fracture (SHIP) study was a 5-year prospective cohort study following community-dwelling older persons admitted to three Sydney hospitals for hip fracture. Information was collected at baseline, and 4 and 12 months, including health status, quality of life, nutritional status, body composition, muscle strength, range of motion, gait velocity, balance, walking endurance, disability, cognition, depression, fear of falling, self-efficacy, social support, physical activity level, vision, and fall-related data, with residential status, disability, and mortality reassessed at 5 years. RESULTS: 193 participants enrolled (81 +/- 8 years, 72% women). High levels of activities of daily living, disability and sedentariness were present prior to fracture. At admission, the cohort had high levels of chronic disease; 38% were depressed, 38% were cognitively impaired, and 26% had heart disease. Seventy-one percent of participants were sarcopenic, 58% undernourished, and 55% vitamin D deficient. Mobility, strength, and vision were severely impaired. There was little evidence that these comorbidities were either recognized or treated during hospitalization. Disability, sedentariness, malnutrition, and walking endurance predicted acute hospitalization length of stay. CONCLUSIONS: The complex comorbidity, pre-existing functional impairment, and sedentary behavior in patients with hip fracture suggest the need for thorough screening and targeting of potentially reversible impairments. Rehabilitation outcomes are likely to be highly dependent on amelioration of these highly prevalent accompaniments to hip fracture.

Effect of power-training intensity on the contribution of force and velocity to peak power in older adults.

OBJECTIVE: To determine the effect of training intensity on the contributions of force and velocity to improvements in peak power (PP) after explosive resistance training in older adults. METHODS: 112 healthy older adults (69 +/- 6 yr) were randomized to explosive resistance training at 20% (G20), 50% (G50), or 80% (G80) maximal strength (1-repetition maximum) for 8-12 wk (twice weekly, 5 exercises, 3 sets of 8 explosive concentric/slow eccentric repetitions) using pneumatic resistance machines or a nontraining control group (CON). RESULTS: Force at peak power (FPP) increased significantly and similarly among training groups compared with CON. Velocity at peak power (VPP) did not improve significantly and remained similar between all groups. Force contributed significantly more to PP production in G80 and G50 than in CON. The change in PP was independently predicted by changes in fat-free mass in G80 and by changes in both FPP and VPP in G50 and G20. CONCLUSION: Explosive resistance training in older adults results in the ability to produce higher PP outputs with heavier loads without loss of movement velocity. Moderate- to high-intensity training induced a greater relative contribution of force to PP production in this cohort.

Continuous hemodynamic response to maximal dynamic strength testing in older adults.

OBJECTIVE: To quantify acute changes in blood pressure and heart rate during a maximal dynamic strength-single-repetition maximum lift (1-RM)-testing session in older adults with a low burden of chronic disease. DESIGN: Descriptive, cross-sectional study. SETTING: University rehabilitation center. PARTICIPANTS: Volunteer sample of 43 community-dwelling, nonresistance-trained older adults aged 60 years and older (mean, 68+/-6y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate was obtained by plethysmography at rest and during 1-RM strength testing on leg press, knee extension, and knee flexion resistance machines. RESULTS: Average resting SBP (132+/-28mmHg), DBP (54+/-15mmHg), and heart rate (65+/-11 beats/min) were independent of hypertensive diagnosis and overweight status. Maximal SBP, DBP, and heart rate increased significantly during the 1-RM in all exercises compared with rest (P<.001). Highest values of SBP (236+/-51mmHg) and DBP (140+/-46mmHg) were measured during the leg press at 99.5%+/-6.7% of 1-RM. Lowest values of SBP (79+/-25mmHg) and DBP (38+/-15mmHg), and the highest (123+/-44 beats/min) and lowest heart rate (41+/-23 beats/min) were measured during the knee extension at 97.4%+/-8.1% of 1-RM. Absolute falls in SBP were greatest in treated hypertensive participants. No cardiovascular symptoms or events occurred in 129 1-RM tests. CONCLUSIONS: Large, very transient, asymptomatic excursions in blood pressure and heart rate were measured during 1-RM testing. The most robust hemodynamic response occurred during the leg press. Thus the leg press may be the most important exercise to focus hemodynamic monitoring efforts upon during strength testing in clinical cohorts.

Estimation of thigh muscle cross-sectional area by dual-energy X-ray absorptiometry in frail elderly patients.

BACKGROUND: Thigh muscle mass and cross-sectional area (CSA) are useful indexes of sarcopenia and the response to treatment in older patients. Current criterion methods are computed tomography (CT) and magnetic resonance imaging. OBJECTIVE: The objective was to compare thigh muscle mass estimated by dual-energy X-ray absorptiometry (DXA), a less expensive and more accessible method, with thigh muscle CSA determined by CT in a group of elderly patients recovering from hip fracture. DESIGN: Midthigh muscle CSA (in cm(2)) was assessed from a 1-mm CT slice and midthigh muscle mass (g) from a 1.3-cm DXA slice in 30 patients (24 women) aged 81 +/- 8 y during 12 mo of follow-up. Fat-to-lean soft tissue ratios were calculated with each technique to permit direct comparison of a variable in the same units. RESULTS: Baseline midthigh muscle CSA was highly correlated with midthigh muscle mass (r = 0.86, P < 0.001) such that DXA predicted CT-determined CSA with an SEE of 10 cm(2) (an error of approximately 12% of the mean CSA value). CT- and DXA-determined ratios of midthigh fat to lean mass were similarly related (intraclass correlation coefficient = 0.87, P < 0.001). When data were expressed as the changes from baseline to follow-up, CT and DXA changes were weakly correlated (intraclass correlation coefficient = 0.51, P = 0.019). CONCLUSIONS: Assessment of sarcopenia by DXA midthigh slice is a potential low-radiation, accessible alternative to CT scanning of older patients. The errors inherent in this technique indicate, however, that it should be applied to groups of patients rather than to individuals or to evaluate the response to interventions.

Power training improves balance in healthy older adults.

BACKGROUND: Age-related decline in muscle power may be an early indicator of balance deficits and fall risk, even in nonfrail adults. This study examined the dose-dependent effect of power training on balance performance in healthy older adults. METHODS: One hundred twelve community-dwelling healthy older adults (69 +/- 6 years) were randomized to 8-12 weeks of power training at 20% (LOW), 50% (MED), or 80% (HIGH) of maximal strength, or a nontraining control (CON) group. Participants trained twice weekly (five exercises; three sets of eight rapid concentric/slow eccentric repetitions) using pneumatic resistance machines. Balance, muscle performance (strength, power, endurance, contraction velocity), and body composition were measured. RESULTS: Power training significantly improved balance performance (p =.006) in participants who underwent power training compared to controls. Low intensity power training produced the greatest improvement in balance performance (p =.048). Average contraction velocity at low load (40% one repetition maximum [1RM]) at baseline independently predicted improvement in balance following training (r = -.29, p =.004). CONCLUSIONS: Power training improves balance, particularly using a low load, high velocity regimen, in older adults with initial lower muscle power and slower contraction. Further studies are warranted to define the mechanisms underlying this adaptation, as well as the optimum power training intensity for a range of physiological and clinical outcomes in older adults with varying levels of health status and functional independence.

Optimal load for increasing muscle power during explosive resistance training in older adults.

BACKGROUND: Muscle power (force x velocity) recedes at a faster rate than strength with age and may also be a stronger predictor of fall risk and functional decline. The optimal training paradigm for improving muscle power in older adults is not known, although some literature suggests high velocity, low load training is optimal in young adults. METHODS: One hundred twelve healthy older adults (69 +/- 6 years) were randomly assigned to either explosive resistance training at 20% (G20), 50% (G50), or 80% (G80) one repetition maximum (1RM) for 8-12 weeks or to a nontraining control group (CON). Participants trained twice per week (five exercises; three sets of eight rapidly concentric and slow eccentric repetitions) using pneumatic resistance machines. Repeated-measures analysis of variance and covariance (ANOVA and ANCOVA) were used to determine the effects of training. RESULTS: Average peak power increased significantly and similarly in G80 (14 +/- 8%), G50 (15 +/- 9%), and G20 (14 +/- 6%) compared to CON (3 +/- 6%) (p < .0001). By contrast, a positive dose-response relationship with training intensity was observed for relative changes in average strength (r = .40, p = .0009) and endurance (r = .43, p = .0005). Average strength increased in G80 (20 +/- 7%), G50 (16 +/- 7%), and G20 (13 +/- 7%) compared to CON (4 +/- 4%) (p < .0001). Average muscle endurance increased in G80 (185 +/- 126%, p < .0001), G50 (103 +/- 75%, p = .0004), and G20 (82 +/- 57%, p = .0078) compared to CON (28 +/- 29%). CONCLUSION: Peak muscle power may be improved similarly using light, moderate, or heavy resistances, whereas there is a dose-response relationship between training intensity and muscle strength and endurance changes. Therefore, using heavy loads during explosive resistance training may be the most effective strategy to achieve simultaneous improvements in muscle strength, power, and endurance in older adults.

A randomized controlled trial of high versus low intensity weight training versus general practitioner care for clinical depression in older adults.

BACKGROUND: Although exercise has been shown to relieve depression, little is known about its mechanism or dose-response characteristics. We hypothesized that high intensity progressive resistance training (PRT) would be more effective than either low intensity PRT or standard care by a general practitioner (GP) in depressed elderly persons, and that high intensity PRT would provide superior benefits in quality of life, sleep quality, and self-efficacy. METHODS: Sixty community-dwelling adults >60 years with major or minor depression were randomized to supervised high intensity PRT (80% maximum load) or low intensity PRT (20% maximum load) 3 days per week for 8 weeks, or GP care. RESULTS: A 50% reduction in the Hamilton Rating Scale of Depression score was achieved in 61% of the high intensity, 29% of the low intensity, and 21% of the GP care group (p =.03). Strength gain was directly associated with reduction in depressive symptoms (r = 0.40, p =.004), as was baseline social support network type (F = 3.52, p =.015), whereas personality type, self-efficacy, and locus of control were unrelated to the antidepressant effect. Vitality quality-of-life scale improved more in the high intensity group than in the others (p =.04). Sleep quality improved significantly in all participants (p <.0001), with the greatest relative change in high intensity PRT (p =.05). CONCLUSIONS: High intensity PRT is more effective than is low intensity PRT or GP care for the treatment of older depressed patients.

Gene expression of collagen types IIA and IX correlates with ultrastructural events in early osteoarthrosis: new applications of the rabbit meniscectomy model.

OBJECTIVE: To examine the phenotypic expression and geographic distribution of collagens in early stages of osteoarthrosis and their relationship to ultrastructural events in cartilage. METHODS: In situ hybridization was used to localize articular expression of total type II (A+B) and type IX collagen at 2 and 4 weeks in the rabbit meniscectomy model of osteoarthrosis. The expression of the developmental marker collagen IIA was analyzed at the same time points. Articular cartilage structure was examined by scanning electron microscopy. RESULTS: Little difference was found in total type II or type IX collagen gene expression for operated versus control limbs at 2 weeks. Gene expression for collagen types IIA and IX was found to be site-specific by the 4 week period and was largely limited to the meniscectomy site. At 4 weeks, this activity was correlated with site-specific alterations in chondrocyte morphology, qualitative changes in the collagen matrix, and articular surface delamination on microscopy. CONCLUSION: Gene expression for collagen types IIA and IX is site-specific and correlates with ultrastructural changes in cartilage in this model of early osteoarthrosis. We present the first known report of the distribution of type IX collagen gene expression in any model of osteoarthrosis. These findings support the central importance of matrix interactions in osteoarthrosis and suggest that early phases of repair involve re-expression of a developmental sequence by chondrocytes.

Chondrogenesis in the regenerating antler tip in red deer: expression of collagen types I, IIA, IIB, and X demonstrated by in situ nucleic acid hybridization and immunocytochemistry.

The annual regrowth of antlers in male deer is a unique example of complete bone regeneration occurring in an adult animal. Growth is initiated at the distal antler tip, which is similar to the epiphyseal growth plate in some respects. However, there is some debate as to whether this process represents "true" endochondral ossification. As part of the characterization of the developmental process in pre-osseus antler tissue, we have studied, by in situ hybridization, the spatial expression of mRNAs for types I, II, and X collagen. Viewed in a coronal plane, type I procollagen mRNA was observed in skin, the fibrous perichondrium, and the densely cellular area immediately adjacent to the perichondrium. Below this area, as cells began to assume a columnar arrangement and coincident with the appearance of a vasculature and synthesis of a cartilaginous matrix, transcripts for types I, IIA, IIB procollagen and X collagen were detected. Further down in the cartilage zone, the pattern of type I procollagen mRNA expression was altered. Here, the signal was detected only in a morphologically distinct subpopulation of small, flattened cells within the intercellular matrix at the periphery of the columns of chondrocytes. The alternative splice form of type II procollagen mRNA (IIA), characteristic of chondroprogenitor cells (Sandell et al. [1991] J. Cell Biol. 114:1307-1319), was expressed by a subset of cells in the upper region of the columns, indicating that this zone contains a population of prechondrocytic cells. Positive hybridization to type IIA was most abundant in these cells. In contrast, transcripts for the other procollagen splice form (IIB) and type X collagen were expressed by chondrocytes throughout the whole of the cartilage region studied. The translation and export of type II collagen and type X collagen were confirmed by detecting specific immunoreactivity for each. The spatial distribution of immunoreactivity for collagen types II and X was consistent with that of corresponding mRNAs. These data demonstrate for the first time the distinct pattern of expression of genes for major cartilage matrix macromolecules, the expression of the differentially spliced form of type II procollagen mRNA (IIA), and specifically the co-localization of types II and X collagen in the developing antler tip. Taken together, they strongly indicate that antler growth involves an endochondral process.

Collagen gene expression during development of avian synovial joints: transient expression of types II and XI collagen genes in the joint capsule.

The developmental sequence of the embryonic joint has been well studied morphologically. There are, however, no definitive studies of cell function during joint development. In order to begin to understand the differentiation events that contribute to joint formation, we examined the expression of collagen mRNAs encoding types I, IIA, IIB, and XI. In situ hybridization was performed on chicken embryo hind limb buds and digits from day 7 to day 18 (Hamburger and Hamilton stages 31-44). In the day 7 (stage 31) limb bud, there was a condensation of mesenchyme forming the primitive tarsal and metatarsal bones that showed abundant expression of type IIA procollagen message, but no type IIB or type alpha 1(XI) message. By day 8 (stage 33), co-expression of types IIA, and type XI procollagen mRNAs was observed in the condensations, with expression of IIB restricted to early chondrocytes with metachromatically staining matrix. At this stage, DNA fragmentation characteristic of apoptosis was observed in cells near the midline of the interzone region between the developing anlagen, and in areas between and around the individual digits of the paddle. The presumptive apoptotic cells were more numerous at day 9 (stage 35), and were not found in the developing joint at subsequent time points, including the initiation of spatial cavitation of the joint. From days 11-18, type IIA procollagen mRNA was expressed in flattened cells at the surface of the anlagen, and in the perichondrium and in the developing joint capsule; type IIB mRNA message was found only in chondrocytes. Type XI mRNA was expressed by all type II-expressing cells. Alpha 1(I) mRNA was expressed early by cells of the interzone and capsule, but as cavitation progressed, the type I expressing cells of the interzone merged with the superficial layer of the articular surface. Thus, at the time of joint cavitation, there was a distinct pattern of expression of procollagen messages at the articular surface, with type I being outermost, followed by morphologically similar cells expressing type IIA, then chondrocytes expressing type IIB. The progenitor cells expressing type IIA message define a new population of cells. These cell populations contribute to the molecular heterogeneity of the articular cartilage, and these same populations likely exist in the developing joints of other species. The transient transcription of type II and type XI collagen genes, characteristic of chondrocytes, by cells in the joint capsule demonstrates that these cells may have chondrogenic potential.

Alternative splice form of type II procollagen mRNA (IIA) is predominant in skeletal precursors and non-cartilaginous tissues during early mouse development.

Type II collagen, generally considered to be characteristic of cartilage, has been localized in specific non-cartilaginous structures during embryogenesis and development of the skeleton. Type II procollagen is synthesized in two different forms generated by alternative splicing of exon 2 in the precursor mRNA transcript. One form (type IIA procollagen) contains a large cysteine-rich domain in the NH2-terminal propeptide, while the second form (type IIB procollagen) does not. These two forms are spatially expressed during development and chondrogenesis with the type IIB procollagen mRNA primarily expressed by chondrocytes while the IIA form is expressed in chondroprogenitor cells (Sandell et al. [1991] J. Cell Biol. 114:1307-1319). The present study demonstrates that the early non-cartilage expression, by somites, mesenchymal and epithelial cells, is predominantly the alternate splice form, type IIA procollagen mRNA. Later in development, the type IIB mRNA splice form is expressed by chondrocytes. During the development of intramembranous bones, such as the mandible, type IIA procollagen mRNA is also expressed. In this tissue, the splice form does not switch to type IIB mRNA and no cartilage is formed. These results show that expression of type IIA mRNA, whether by epithelial or mesenchymal cells, precedes formation of overt skeletal structures.

Psychobehavioral disturbance in epileptic children.

Psychobehavioral disturbances are frequently seen in epileptic children, but they vary in type and degree. This diversity depends on various factors: age at onset, type of epileptic syndrome and EEG pattern, and the drugs used. The early onset of an epileptic process (within the first year of life) has a profound effect on the organization of primary relational processes and on structuring of the ego. The cognitive and behavioral damage that results may become evident after just a few seizures and may persist through time when such damage is not definitive. Epilepsy with onset in childhood may be accompanied by practognosic deficits and impairment of memory, attention and analytical reasoning. These deficits occur much more frequently in the symptomatic forms. In adolescent forms of epilepsy prevalently idiopathic, disturbances of a neurotic type are relatively common. Psychobehavioral disturbances tied to drugs can be noticed mainly with the use of phenobarbital (hyperactivity, longer reaction times), phenytoin (torpor), and politherapy.

The risk of convulsions: a longitudinal study of normal babies and infants with neonatal damage in the first 6 years of life.

After carefully reviewing the epidemiological literature on this subject, we assessed the risk of febrile, isolated or epileptic convulsions in normal babies and infants with neonatal damage. We considered 417 term or preterm infants with birth injury and compared them with 400 healthy full-term newborns, all born between 1978 and 1980, studying each one individually until at least the age of 6 using the chi 2 test, the risk factors in relation to the convulsive outcome in all the groups were processed. We also calculated the relative risk of outcome of both febrile convulsions and epilepsy. Our results show that as far as the onset of seizure disorders in the term infant is concerned, the predisposing factors are asphyxia, neurological syndrome, and previous barbiturate intake. In contrast with this, for premature infants the risk factors are severe apnea and severe prematurity.

State of the art of magnetic resonance (MR) in neonatal hypoxic-ischemic encephalopathy.

Magnetic resonance (MR) has begun to play an important role in neonatal neurology. Several MRI techniques have been applied to the diagnosis of hypoxic ischemic encephalopathy. Cerebral perfusion examined by intravoxel incoherent motion, a non-invasive tool, seems to be opening new inroads for detecting variations (neurophysiological modifications) in cerebral flows during hypoxic ischemic encephalopathy. MR spectroscopy allows identification of specific biochemical alteration of spectra patterns at various moments of hypoxic ischemic distress, including: (1) primary expression of metabolic disorders induced by the lack of blood and O2, revealed by a peak of the water-suppressed H1 spectrum, the earliest and most persistent-marker; (2) a secondary marker for the establishment of permanent lesions of anoxic-ischemic origin revealed that variations of the phosphocreatine/inorganic phosphorous index in the P31 spectrum are of diagnostic and prognostic significance in this phase. In relation to different neuropathological, structural lesions, MRI becomes particularly important in diagnosing the acute phase of cerebral edema and the different types of infarct. MRI is especially fruitful in monitoring the evolution of the lesion, providing an evaluation of myelinization, and defining the neuropathological outlook. Spectroscopic studies on human neonates have helped establish the therapeutic effects of mannitol in cerebral metabolism. MR studies on neonate animals seem to open new therapeutic prospect for CA antagonists.