Serum osteocalcin in relation to calcaneal bone mineral density in elderly men and women: a 5-year follow-up

A 5-year follow-up study investigated serum concentrations of total (tOC) and intact (iOC) osteocalcin in relation to calcaneal bone mineral density (BMD). The study comprised two cohorts, 75- and 80-year-olds, both resident in the city of Jyv?skyl?, Finland. Baseline OC and BMD were obtained for 161 men and 233 women, of whom 83 men and 189 women participated in follow-up bone measurements. The mean concentration of tOC increased from 9.6 ± 4.3 to 13.2 ± 8.5 μg/l (P = 0.001) in men and from 11.2 ± 4.9 to 14.0 ± 6.1 μg/l (P < 0.001) in women, whereas mean iOC decreased from 6.4 ± 3.0 to 5.9 ± 3.0 μg/l (P = 0.273) and from 7.7 ± 3.7 to 6.9 ± 3.4 μg/l (P = 0.021) in men and women, respectively. TOC and iOC levels correlated inversely with BMD and change in BMD in both sexes (r ranged from −0.223 to −0.422 and P = 0.048 ≤ 0.001). When we divided the baseline tOC and iOC values into four quartiles, the decrease in BMD was significantly greater in the third tOC quartiles in women and in the fourth tOC and iOC quartiles in men when compared with the lower quartiles. During the 5-year period, 19 men and 59 women sustained at least one fracture. These individuals with fractures had significantly higher iOC values and tended to have higher tOC values compared with the nonfracture group at baseline (P = 0.038 and 0.087, respectively). Our results indicate that baseline serum tOC and iOC were associated with bone loss and predicted fracture in the two cohorts of independently living elderly men and women. Received: December 16, 2000 / Accepted: July 23, 2001     

Learning-induced neural plasticity of speech processing before birth

Learning, the foundation of adaptive and intelligent behavior, is based on plastic changes in neural assemblies, reflected by the modulation of electric brain responses. In infancy, auditory learning implicates the formation and strengthening of neural long-term memory traces, improving discrimination skills, in particular those forming the prerequisites for speech perception and understanding. Although previous behavioral observations show that newborns react differentially to unfamiliar sounds vs. familiar sound material that they were exposed to as fetuses, the neural basis of fetal learning has not thus far been investigated. Here we demonstrate direct neural correlates of human fetal learning of speech-like auditory stimuli. We presented variants of words to fetuses; unlike infants with no exposure to these stimuli, the exposed fetuses showed enhanced brain activity (mismatch responses) in response to pitch changes for the trained variants after birth. Furthermore, a significant correlation existed between the amount of prenatal exposure and brain activity, with greater activity being associated with a higher amount of prenatal speech exposure. Moreover, the learning effect was generalized to other types of similar speech sounds not included in the training material. Consequently, our results indicate neural commitment specifically tuned to the speech features heard before birth and their memory representations.During the fetal period the brain undergoes extensive developmental changes as new synapses are formed (1) and axonal connections between neurons are myelinated (2), facilitating efficient recognition and analysis of complex information. In audition, the functional maturation of the developing nervous system is driven by external input, which is evidenced by, for instance, the rapid reorganization of the auditory cortex by external stimuli soon after the onset of hearing in rats (3). This was suggested to occur in humans usually by the gestational age of 27 wk (4). Such plastic changes in neural assemblies during early development indicate that humans have some learning capability even before birth (5, 6). However, this learning capability may be based predominantly on the discrimination of low-pitched sounds that can penetrate the intrauterine walls (7–9). This low-pitch information may play an important role in early speech discrimination of newborns (10) by facilitating learning to segment incoming speech into meaningful units.Consistent with this, previous behavioral studies have shown that fetuses become attuned to a variety of features of the surrounding auditory environment. For example, fetuses habituate to the native language of the environment or of the mother (11, 12), familiar melodies (13) or fragments of stories heard during pregnancy (14), and even the mother’s voice (15). In addition to learning-based habituation involving the laterobasal amygdala only (16), fetuses, for example, react differently to native and nonnative vowels (17) or familiar and unfamiliar melodic contours (18) and discriminate between different vowels of their native language (19). This capability for fine-tuned auditory processing and discrimination suggests that memory traces lasting for several days in the auditory cortex (20) are formed as a result of fetal learning. These neural memory traces are a prerequisite for effective recognition, categorization, and understanding of speech (21), enabling newborns to generate specific learned behaviors. For example, at birth, neonates cry with their native language prosody (22).If neural memory traces for individual sounds are formed in utero, then this should be reflected after birth by changes in the brain’s electric activity—namely, by the emergence and enhancement of the mismatch response (MMR) to sound changes (23). The MMR, the infant analogy to the adult mismatch negativity (MMN), represents the brain’s automatic change detection system (24) and is elicited by any discriminable change in the learned material, therefore indirectly reflecting the underlying neural representations of learned repetitive (“standard”) stimuli, such as those for native language speech sounds. Consequently, the MMR indices of cortical discrimination accuracy and plasticity (23, 25, 26) are elicited irrespective of whether or not the individual is attending to sound stimuli (27) and can be recorded from sleeping infants (23, 28) and, with magnetoencephalography, even from fetuses (29).We investigated the prenatal formation of neural memory traces for speech sounds by comparing the neural dynamics and the MMRs of newborns who had or had not been exposed to novel speech material as fetuses with each other. Starting from pregnancy week 29 until birth, the infants in the learning group were exposed to a trisyllabic pseudoword, [tatata], and two infrequently presented changes: a vowel change (in the middle syllable, [tatota]) or a pitch change ([tatata] with pitch modifications of the middle syllable). These speech sequences were presented in three separate parts, which were interspersed with nonvocal music. The learning effects were investigated in these infants after their birth by recording neural responses to the infrequent vowel and pitch changes used in the training material. In addition, generalization of the learning effects was determined by recording neural responses to unfamiliar changes of vowel intensity ([tatata]) and vowel duration ([tata:ta]) in the middle syllable. For comparison, neural responses to all of these stimuli were also recorded from a naive control group. To ensure that the basic auditory abilities of both groups were comparable, neural responses were also recorded for pitch changes of tones equally unfamiliar for both groups.We expected selective learning effects for the pseudoword with the pitch changes because pitch changes seldom occur in the middle of words in Finnish, the language of the infants’ environment. In contrast, both groups should show similar MMRs for a vowel identity change, previously observed in newborns (30, 31), because both groups had heard vowels in utero, being surrounded by the Finnish language environment, which is rich in vowels (32).     

Magnetic resonance imaging findings of the pancreas in patients with Shwachman-Diamond syndrome and mutations in the SBDS gene

Pancreatic MRI was evaluated in 14 patients with a clinical diagnosis of Shwachman-Diamond syndrome, and the findings were correlated with Shwachman-Bodian-Diamond gene (SBDS) genotype. The findings suggest that patients with mutations in the SBDS gene have a characteristic magnetic resonance imaging pattern of fat-replaced pancreas and that SBDS mutations are unlikely in patients without this pattern.     

Normal growth and intravascular volume status with good metabolic control during peritoneal dialysis in infancy

The most demanding patient population on peritoneal dialysis (PD) consists of children under 2 years of age. Their growth is inferior to that of older children and maintaining euvolemia is difficult, especially in anuric patients. In this prospective study reported here, we enrolled 21 patients <2 years of age (mean 0.59 years) at onset of PD and monitored their uremia parameters and evaluated their nutrition. Since no good instrument currently exists for estimating intravascular volume status, we used traditional blood pressure measurements, echocardiography, and N-terminal atrial natriuretic peptide measurements. Growth was compared with midparental height. Metabolic control was good. Long-term hypertension was seen in 43% of the patients, but left ventricular hypertrophy decreased during the study period. Mean weekly urea Kt/V was 3.38 ± 0.66 and creatinine clearance was 49 ± 20 L/week per 1.73 m². Catch-up growth was documented in 57% of the patients during PD. However, these children did not attain their midparental height at the end of PD at a mean age of 1.71 years. Although favorable metabolic control and good growth were achieved during PD, these children lagged in term of their midparental height. We conclude that several instruments are needed for determining the management of intravascular volume status and that the control of calcium–phosphorus status is demanding.     

Self-rated health and mortality in older men and women: a time-dependent covariate analysis

Although the relation between self-rated health (SRH) and mortality is widely known, most of the studies have relied in baseline measurements unheeding the dynamics of the phenomenon. Our aim was to analyze how SRH both as a constant and as a time-dependent covariate predicts mortality in older men and women and to compare these different approaches. Subjects consisted of 110 male and 208 female (n=318) residents in the city of Jyv?skyl?, central Finland, aged 75 years at the baseline in 1989. The follow-up data was gathered in 1994 and mortality was followed for 10 years. Results showed that poor SRH was strongly associated with higher mortality risk in women in all models. In men, the association was found only in time-dependent and 5 year follow-up models and these associations were explained by baseline health status. To conclude, our analyses showed that there are gender differences in association between SRH and mortality and that the use of time-dependent covariate in a Cox regression model enables advantage to be taken of all the information in a longitudinal study design.     

Transesophageal echocardiography in the diagnosis of thrombosis associated with permanent transvenous pacemaker electrodes

OBJECTIVES: We sought to assess the value of transesophageal echocardiography (TEE) in the diagnosis of PM-lead-associated central venous thrombi. BACKGROUND: Venous thrombosis is not infrequent after pacemaker (PM) or implantable cardioverter-defibrillator (ICD) implantation. Previous incidence studies of thrombosis have been based on venography or Doppler ultrasound, but the role of TEE has not been systematically evaluated in this setting. METHODS: Study group comprised 66 consecutive patients (mean age 64 years, 67 % male) referred for implantation of their first PM or ICD and with a successful TEE, transthoracic echocardiography (TTE) and venography at 6 months after implantation. The total number of implanted leads was 110. During the 6 months of clinical follow-up, nuclear ventilation-perfusion scan or spiral computed tomography was performed when symptoms aroused a clinical suspicion of PE. RESULTS: TEE revealed a right atrium (RA) or lower superior vena cava (SVC) thrombus in 6 (9%) patients. These thrombi were not visualized by TTE or venography. Additionally, 12 (20%) patients were found to have venographic subclavian or innominate vein thrombi, but none of those could be diagnosed with TEE. Symptomatic pulmonary embolism (PE) was diagnosed in two and an asymptomatic PE in one individual and two of these occurred among the six patients with a thrombus in TEE. No clinical predictors for thrombosis were found. CONCLUSIONS: TEE is an excellent method to visualize electrodes within the RA and proximal SVC. Electrode-associated RA thrombi appear to be relatively common after PM implantation, and they may remain undetectable by venography or TTE. Although these thrombi are mostly asymptomatic, they can give rise to pulmonary embolism and should also be kept in mind in the differential diagnosis of endocarditis. TEE is the method of choice for the diagnosis of these lesions.     

Late urologic sequelae after surgery for congenital sacrococcygeal teratoma

Forty-five patients treated for congenital sacrococcygeal teratoma were examined for late urologic outcome. The follow-up ranged from 4 to 42 (median 22) years. Only 8 patients experienced subjective urinary complaints. Sonography of the urinary tract revealed unilateral hydronephrosis in 2 patients, an ectopic kidney in 1, and a severely scarred kidney in 1; 1 patient had asymptomatic bacteriuria. Urodynamic screening using uroflowmetry was abnormal in 35 patients (78%). The risk of significant postoperative complications and subsequent late sequelae was greatest among patients with intrapelvic extension of the primary tumor.Supported by the Foundation for Pediatric Research, Helsinki, Finland     

The Hepatic Glucuronate Pathway in the Rat after Treatment with 3,3′,5-Triiodothyronine and Phenobarbital

Abstract The hepatic D-glucuronic acid pathway was studied in male rats after administration of 3, 3′, 5-triidothyronine (20 μg intraperitoneally daily, for three weeks). Some of the key enzymes of the pathway showed decreased activities during hyperthyroidism. D-glucuronolactone dehydrogenase, UDPglucuronosyltransferase and UDPglucuronic acid pyrophosphatase were not affected, whilst the activity of β-glucuronidase was significantly increased. D-Glucaric acid excretion in urine was enhanced and that of L-ascorbic acid was decreased. Phenobarbital administered to hyperthyroid and euthyroid animals (80 mg/kg intraperitoneally, daily, for 3 days) did not markedly affect the differences in the enzyme activities between the two groups. UDP-Glucuronosyltransferase and D-glucuronolactone dehydrogenase activities were induced, and in the case of UDPglucuronosyltransferase the induction was more pronounced during hyperthyroidism. D-Glucaric acid excretion in the urine was increased by phenobarbital treatment both in hyperthyroid and normal animals. L-Ascorbic acid excretion was also increased, but the increase was greater in euthyroid than in hyperthyroid animals. The results suggest that hyperthyroidism favours the metabolism of free D-glucuronic acid towards the formation of D-glucaric acid. Treatment with phenobarbital, however, also enhances to some extent the biosynthesis of L-ascorbic acid.