Cardiovascular reflex tests detect autonomic dysfunction in symptomatic and pre-symptomatic subjects with hereditary transthyretin amyloidosis.

PURPOSE: Autonomic dysfunction is a distinctive but undervalued feature of hereditary transthyretin amyloidosis (ATTRv). It may predate the onset of polyneuropathy and cardiomyopathy, thereby providing crucial prognostic and therapeutic information. The objective of this study was to assess autonomic function by means of the standardized cardiovascular autonomic reflex tests (CRTs) in a cohort of subjects with genetically proven ATTRv from non-endemic areas who were in the symptomatic and pre-symptomatic stages. METHODS: All subjects enrolled in this cross-sectional study had genetically proven ATTRv. They underwent the head-up tilt test, Valsalva manoeuvre, deep breathing test, cold face test and handgrip test while under continuous blood pressure and heart rate monitoring. Based on the results of the nerve conduction study, the subjects were divided into two groups: those with polyneuropathy (ATTRv-wPN) and those without polyneuropathy (ATTRv-woPN). Age- and sex-matched healthy controls (HC) were used for comparison. RESULTS: Thirty-seven ATTRv subjects (19 with ATTRv-wPN, 18 with ATTRv-woPN) and 41 HC performed the CRTs. Of these 37 subjects with ATTRv, four (11%) presented neurogenic orthostatic hypotension the during head-up tilt test. Based on the results of the CRTs, autonomic dysfunction characterized by either sympathetic or parasympathetic impairment was detected in 37% and 63% of ATTRv-wPN subjects, respectively. Subjects with ATTRv-woPN presented a significant impairment of autonomic responses to the Valsalva manoeuvre compared to the HC (overshoot p = 0.004; Valsalva ratio p = 0.001). CONCLUSION: Autonomic dysfunctions are frequent in subjects with ATTRv when investigated by means of standardized CRTs, and are also relevant in the pre-symptomatic stage. Cardiovagal functions are the primary functions affected, among others. This may be crucial in defining the proper diagnostic workout for early diagnosis and improving the likelihood of providing the patient with prompt administration of disease-modifying treatments.

Trends in severe outcomes in SARS-CoV-2-positive hospitalized patients with rheumatic diseases: a monocentric observational and case-control study in northern Italy.

Rheumatic disease patients are at greater risk of infection due to their disease, comorbidities, and immunosuppressive therapy. COVID-19 outcomes in this patient setting appeared to be similar to those of the general population. However, data on this topic were mainly related to small studies on a limited number of patients. Consequently, to date, this field remains poorly explored, particularly in the pre-vaccine era. This monocentric study aimed to describe the intrahospital mortality in rheumatic patients with SARS-CoV-2 consecutively hospitalized from 21 February to 31 December 2020, before anti-SARS-CoV-2 vaccine administration spread, compared with non-rheumatic patients. Of 2491 included patients, 65 [3%, median (interquartile range) age 75 (64.76-82.239 years, 65% women] were suffering from rheumatic diseases. A total of 20 deaths were reported [case fatality rate 31%, 95% confidence interval (CI): 19-42] compared with 433 deaths (19%, 95% CI: 17-20) in patients without rheumatic diseases (p=0.024). However, the rheumatic disease was not associated with a significant increase in univariate mortality hazards (hazard ratio 1.374, 95% CI: 0.876-2.154), and after adjustment (hazard ratio 1.199, 95% CI: 0.759-1.894) by age, sex and Charlson comorbidity index. The incidence of intensive care unit admission, death, and discharge in the case-control study was comparable between rheumatic and non-rheumatic patients. The presence of rheumatic diseases in SARS-CoV-2-hospitalized patients did not represent an independent risk factor for severe disease or mortality.

Pathway specific activation of ventral hippocampal cells projecting to the prelimbic cortex diminishes fear renewal.

The ability to learn that a stimulus no longer signals danger is known as extinction. A major characteristic of extinction is that it is context-dependent, which means that fear reduction only occurs in the same context as extinction training. In other contexts, there is re-emergence of fear, known as contextual renewal. The ability to properly extinguish fear memories and generalize safety associations to multiple contexts provides therapeutic potential, but little is known about the specific neural pathways that mediate fear renewal and extinction generalization. The ventral hippocampus (VH) is thought to provide a contextual gating mechanism that determines whether fear or safety is expressed in particular contexts through its projections to areas of the fear circuit, including the infralimbic (IL) and prelimbic (PL) cortices. Moreover, VH principal cells fire in large, overlapping regions of the environment, a characteristic that is ideal to support generalization; yet it is unclear how different projection cells mediate this process. Using a pathway-specific (intersectional) chemogenetic approach, we demonstrate that selective activation of VH cells projecting to PL attenuates fear renewal without affecting fear expression. These results have implications for anxiety disorders since they uncover a neural pathway associated with extinction generalization.

My Mind Project: the effects of cognitive training for elderly-the study protocol of a prospective randomized intervention study.

BACKGROUND: Cognitive decline and dementia represent a key problem for public health as they heavily impair social functioning and independent living. The development of new strategies to support recommendations for patients and their caregivers may represent an outstanding step forward. AIMS: To describe the study protocol and methods of "My Mind Project: the effect of cognitive training for elderly" (Grant No. 154/GR-2009-1584108), which investigates, by the use of a multidisciplinary approach, the effects of a comprehensive cognitive training programme on performances in aged subjects with mild-moderate Alzheimer's disease, mild cognitive impairment and normal cognitive functioning. METHODS: The study is a prospective randomized intervention for the assessment of cognitive training effects in three groups of elderly subjects with different cognitive status. A total of 321 elderly people were enrolled in Marche Region, Italy. Each subject was randomly assigned to an experimental group or to a control group. Cognitive performances and biochemical blood markers have also been analysed before cognitive training (baseline), immediately after termination (follow-up 1), after 6 months (follow-up 2) and after 2 years (follow-up 3). DISCUSSION: The results will be useful to identify some efficient programmes for the enhancement of cognitive performance in elderly with and without cognitive decline. CONCLUSION: The application of a non-pharmacological approach in the treatment of elderly with cognitive disorders could have a profound impact on National Health Service.

Mystery of the memory engram: History, current knowledge, and unanswered questions.

The quest to understand the memory engram has intrigued humans for centuries. Recent technological advances, including genetic labelling, imaging, optogenetic and chemogenetic techniques, have propelled the field of memory research forward. These tools have enabled researchers to create and erase memory components. While these innovative techniques have yielded invaluable insights, they often focus on specific elements of the memory trace. Genetic labelling may rely on a particular immediate early gene as a marker of activity, optogenetics may activate or inhibit one specific type of neuron, and imaging may capture activity snapshots in a given brain region at specific times. Yet, memories are multifaceted, involving diverse arrays of neuronal subpopulations, circuits, and regions that work in concert to create, store, and retrieve information. Consideration of contributions of both excitatory and inhibitory neurons, micro and macro circuits across brain regions, the dynamic nature of active ensembles, and representational drift is crucial for a comprehensive understanding of the complex nature of memory.

Experimental constraints on left-right symmetric models from muon decay.

The TWIST Collaboration has completed a new measurement of the energy-angle spectrum of positrons from the decay of highly polarized muons. A simultaneous measurement of the muon decay parameters ρ, δ, and P(µ)(π)ξ tests the standard model in a purely leptonic process and provides improved limits for relevant extensions to the standard model. Specifically, for the generalized left-right symmetric model |(g(R)/g(L))ζ|<0.020 and (g(L)/g(R))m(2)>578 GeV/c(2), both 90% C.L.

Behavioural features of Italian infants and young adults with Williams-Beuren syndrome.

BACKGROUND: The increased interest in social interaction in Williams-Beuren syndrome (WBS) is evident from infancy onwards, together not only with increased empathy, positive interpersonal bias, but also with social disinhibition. Previous studies have described behavioural and emotional problems as being widely represented in WBS. There is limited scope for comparisons between literature data because of the variety of instruments used to assess behaviour. METHOD: Forty-one children and young adults with WBS were enrolled and underwent general cognitive assessment. In order to compare our data with the literature, we used standardised questionnaires used in previous studies (Developmental Behaviour Checklist: DBC-P). General cognitive abilities, gender and age were included in the analysis. RESULTS: Behavioural problems were more relevant than expected according to intellectual impairment. Some features were present at any age: inattention, anxiety, disruptive behaviours. Antisocial conduct was almost absent; perseverative conduct, a poor sense of danger and, more generally, self-absorbed behaviours tended to diminish along with age and to be linked to more pronounced cognitive impairment. CONCLUSION: As previously described for other countries, behaviour disturbances occur frequently in the Italian WBS population. Our data could support the existence of some 'intrinsic' behavioural characteristics in WBS such as inattention and anxiety, which are detectable and important at any age; both learning and social exposure to a structured context such as school could help diminish self-absorbed behaviour.

COVID-19 and the forgotten pandemic: follow-up of neurocognitive disorders during lockdown in Argentina. / COVID-19 y la pandemia olvidada: el seguimiento de las enfermedades neurocognitivas durante la cuarentena en Argentina.

INTRODUCTION: Health systems in numerous countries around the world are suffering a serious burden as a consequence of the COVID-19 pandemic. As a result of this situation, the follow-up of such chronic diseases as dementia may be at risk. Similarly, neuropsychiatric complications related to lockdown measures may also be neglected; Argentina's lockdown has been the longest implemented in Latin America. This study aims to determine the frequency of the different types of medical consultations for neurocognitive disorders and the predictors for requiring consultation since the beginning of the lockdown. METHODS: We performed a descriptive, observational, cross-sectional study based on data collected through an online survey. RESULTS: Data were collected on 324 participants, with 165 (50.9%) having had at least one medical consultation. Consultations were held by telephone in 109 cases (33.6%), by e-mail in 62 (19.1%), by video conference in 30 (9.3%), and at the emergency department in 23 (7.1%). Predictors of requiring consultation were Clinical Dementia Rating scores ≥1 (P<.001) and diagnosis of Alzheimer disease (P=.017). Higher Neuropsychiatric Inventory scores were found in the group of respondents who did require medical consultation (P<.001), but no significant differences were found between groups for Zarit Burden Interview scores. CONCLUSION: We identified a high prevalence of behavioural disorders and caregiver burden during lockdown. Nevertheless, only 50% of respondents had sought medical consultation (by telephone or email in 52.7% of cases). Care of people with dementia must be emphasised, guaranteeing follow-up of these patients.

Major histocompatibility complex-independent recognition of a distinctive pollen antigen, most likely a carbohydrate, by human CD8+ alpha/beta T cells.

We have isolated CD8+ alpha/beta T cells from the blood of atopic and healthy individuals which recognize a nonpeptide antigen present in an allergenic extract from Parietaria judaica pollen. This antigen appears to be a carbohydrate because it is resistant to proteinase K and alkaline digestion, is hydrophilic, and is sensitive to trifluoromethane-sulphonic and periodic acids. In addition, on a reverse-phase high performance liquid chromatography column the antigen recognized by CD8(+) T cells separates in a fraction which contains >80% hexoses (glucose and galactose) and undetectable amounts of proteins. Presentation of this putative carbohydrate antigen (PjCHOAg) to CD8+ T cell clones is dependent on live antigen presenting cells (APCs) pulsed for >1 h at 37 degrees C, suggesting that the antigen has to be internalized and possibly processed. Indeed, fixed APCs or APCs pulsed at 15 degrees C were both unable to induce T cell response. Remarkably, PjCHOAg presentation is independent of the expression of classical major histocompatibility complex (MHC) molecules or CD1. CD8+ T cells stimulated by PjCHOAg-pulsed APCs undergo a sustained [Ca2+]i increase and downregulate their T cell antigen receptors (TCRs) in an antigen dose- and time-dependent fashion, similar to T cells stimulated by conventional ligands. Analysis of TCR Vbeta transcripts shows that six independent PjCHOAg-specific T cell clones carry the Vbeta8 segment with a conserved motif in the CDR3 region, indicating a structural requirement for recognition of this antigen. Finally, after activation, the CD8+ clones from the atopic patient express CD40L and produce high levels of interleukins 4 and 5, suggesting that the clones may have undergone a Th2-like polarization in vivo. These results reveal a new class of antigens which triggers T cells in an MHC-independent way, and these antigens appear to be carbohydrates. We suggest that this type of antigen may play a role in the immune response in vivo.

Kinetics of pronuclear development and the effects of vector type and timing of injection on the efficiency of gene transfer into rhesus macaque embryos.

A series of experiments was performed to determine the dynamics of pronuclear development as well as the efficiency of either adenovirus-associated (AAV) or lentivirus-derived vectors to introduce a green fluorescent protein (GFP) reporter gene into rhesus macaque (Macaca mulatta) embryos. Assessment of pronuclear development at various times after fertilization revealed that the appearance of pronuclei was determined by the presence of the first and the timing of the second polar body. The dynamics of pronuclear formation was a significant determinant of whether an oocyte reached the blastocyst stage, however, when the percentage of blastocysts were based on the number of zygotes, the timing of the appearance of polar bodies did not appear to have any effect on subsequent development. Injection of different AAV-derived vectors showed that the serotype of the vector did not affect development or the proportion of transgenic embryos. Moreover, all putative transgenic embryos proved to be expression mosaics. Injection of embryos with lentiviral vectors showed that timing of injection (before or after fertilization) had no effect on subsequent transgene expression, but that the type of reporter gene determined post-injection development and rate of transgenesis. The transfer of embryos following injection of a lentiviral vector into three recipients resulted in one pregnancy which was lost during the second trimester. Analysis of fetal tissues showed ubiquitous presence of the transgene and GFP expression in all tissues examined. These results show that lentivirus-derived vectors can efficiently transform rhesus embryos and are suitable for the generation of transgenic rhesus monkeys.

Psychosocial and biochemical interactions in aging: preliminary results from an Italian old sample of "Zincage" project.

The study of the interactions among biological factors and psychosocial conditions is a very innovative field, because data are lacking in the scientific literature. Among biological aspects, zinc is an essential element in the elderly, especially in relation to one of the proteins, such as albumin, involved in zinc transport into the cells. In this study, the aim is the assessment of the interrelationship between albumin value (used as an index of the body zinc status) and some psychosocial dimensions in elderly Italian sample recruited for ZINCAGE project, supported by the European Commission in the "Sixth Framework Programme". Some tests and questionnaires were administered to older people included in the trial: the "life-style questionnaire"; the mini mental state examination (MMSE); the geriatric depression scale (GDS-15 items). On the basis of the Senieur Protocol for gerontological studies, a sample of 291 Italian healthy old subjects has been recruited in Central Italy and divided into 3 age groups: (a) 125 subjects aged from 65 to 74 years, (b) 89 subjects aged from 75 to 84 years, (c) 77 subjects aged >or=85 years (classified like successful old people). No cognitive impairment assessed by MMSE was observed in 67.5% of the sample; 64.0% had GDS score less than 5, indicating no depression, whereas the prevalence of biological albumin deficiency (<3.5 g/dl) found in Italian old people was 21.0%. Sixty one percent of subjects with albumin deficiency displayed higher values of GDS (>or=5). These preliminary results showed an interrelationship among serum albumin value and psychosocial aspects in Italian old population, suggesting that low albumin values may be involved in impaired psychological dimensions.

Bryostatin enhancement of memory in Hermissenda.

Bryostatin, a potent agonist of protein kinase C (PKC), when administered to Hermissenda was found to affect acquisition of an associative learning paradigm. Low bryostatin concentrations (0.1 to 0.5 ng/ml) enhanced memory acquisition, while concentrations higher than 1.0 ng/ml down-regulated the pathway and no recall of the associative training was exhibited. The extent of enhancement depended upon the conditioning regime used and the memory stage normally fostered by that regime. The effects of two training events (TEs) with paired conditioned and unconditioned stimuli, which standardly evoked only short-term memory (STM) lasting 7 min, were--when bryostatin was added concurrently--enhanced to a long-term memory (LTM) that lasted about 20 h. The effects of both 4- and 6-paired TEs (which by themselves did not generate LTM), were also enhanced by bryostatin to induce a consolidated memory (CM) that lasted at least 5 days. The standard positive 9-TE regime typically produced a CM lasting at least 6 days. Low concentrations of bryostatin (<0.5 ng/ml) elicited no demonstrable enhancement of CM from 9-TEs. However, animals exposed to bryostatin concentrations higher than 1.0 ng/ml exhibited no behavioral learning. Sharp-electrode intracellular recordings of type-B photoreceptors in the eyes from animals conditioned in vivo with bryostatin revealed changes in input resistance and an enhanced long-lasting depolarization (LLD) in response to light. Likewise, quantitative immunocytochemical measurements using an antibody specific for the PKC-activated Ca2+/GTP-binding protein calexcitin showed enhanced antibody labeling with bryostatin. Animals exposed to the PKC inhibitor bisindolylmaleimide-XI (Ro-32-0432) administered by immersion prior to 9-TE conditioning showed no training-induced changes with or without bryostatin exposure. However, if animals received bryostatin before Ro-32, the enhanced acquisition and demonstrated recall still occurred. Therefore, pathways responsible for the enhancement effects induced by bryostatin were putatively mediated by PKC. Overall, the data indicated that PKC activation occurred and calexcitin levels were raised during the acquisition phases of associative conditioning and memory initiation, and subsequently returned to baseline levels within 24 and 48 h, respectively. Therefore, the protracted recall measured by the testing regime used was probably due to bryostatin-induced changes during the acquisition and facilitated storage of memory, and not necessarily to enhanced recall of the stored memory when tested many days after training.

In vitro fertilization in the pigtailed macaque (Macaca nemestrina).

The objective of this study was to investigate the possibility of collecting oocytes and semen from pigtailed macaques (Macaca nemestrina) and to establish a protocol for the production of viable embryos that would be suitable for transfer into surrogate females. A total of 82 oocytes were collected from a total of four females (on 2 d with two females each). Semen was collected from the same male on both occasions with respective ejaculate volumes of 0.55 and 0.1 mL containing 2 x 10(9) and 6.6 x 10(8)sperm/mL. Following insemination and after 48 h in culture, 42 (51.2%) of the oocytes had cleaved. Of these, 21 were selected based on developmental stage and their morphology and cryopreserved. The remainder was kept in culture for an additional 5 d, at which time three had reached the expanded blastocyst stage. A total of five transfers were performed with frozen-thawed embryos; two of these resulted in pregnancies and the birth of infants. The results of this study demonstrated that oocytes can be retrieved from pigtailed macaques and that such oocytes can be inseminated and cultured in vitro to the blastocyst stage and give rise to viable offspring after transfer into surrogate females.

Whole-Brain DTI Assessment of White Matter Damage in Children with Bilateral Cerebral Palsy: Evidence of Involvement beyond the Primary Target of the Anoxic Insult.

BACKGROUND AND PURPOSE: Cerebral palsy is frequently associated with both motor and nonmotor symptoms. DTI can characterize the damage at the level of motor tracts but provides less consistent results in nonmotor areas. We used a standardized pipeline of analysis to describe and quantify the pattern of DTI white matter abnormalities of the whole brain in a group of children with chronic bilateral cerebral palsy and periventricular leukomalacia. We also explored potential correlations between DTI and clinical scale metrics. MATERIALS AND METHODS: Twenty-five patients (mean age, 11.8 years) and 25 healthy children (mean age, 11.8 years) were studied at 3T with a 2-mm isotropic DTI sequence. Differences between patients and controls were assessed both voxelwise and in ROIs obtained from an existing DTI atlas. Clinical metrics included the Gross Motor Function Classification System, the Manual Ability Classification System, and intelligence quotient. RESULTS: The voxel-level and ROI-level analyses demonstrated highly significant (P < .001) modifications of DTI measurements in patients at several levels: cerebellar peduncles, corticospinal tracts and posterior thalamic radiations, posterior corpus callosum, external capsule, anterior thalamic radiation, superior longitudinal fasciculi and corona radiata, optic nerves, and chiasm. The reduction of fractional anisotropy values in significant tracts was between 8% and 30%. Statistically significant correlations were found between motor impairment and fractional anisotropy in corticospinal tracts and commissural and associative tracts of the supratentorial brain. CONCLUSIONS: We demonstrated the involvement of several motor and nonmotor areas in the chronic damage associated with periventricular leukomalacia and showed new correlations between motor skills and DTI metrics.

Quantitative Evaluation of Performance during Robot-assisted Treatment.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Methodologies, Models and Algorithms for Patients Rehabilitation". OBJECTIVES: The great potential of robots in extracting quantitative and meaningful data is not always exploited in clinical practice. The aim of the present work is to describe a simple parameter to assess the performance of subjects during upper limb robotic training exploiting data automatically recorded by the robot, with no additional effort for patients and clinicians. METHODS: Fourteen children affected by cerebral palsy (CP) performed a training with Armeo®Spring. Each session was evaluated with P, a simple parameter that depends on the overall performance recorded, and median and interquartile values were computed to perform a group analysis. RESULTS: Median (interquartile) values of P significantly increased from 0.27 (0.21) at T0 to 0.55 (0.27) at T1 . This improvement was functionally validated by a significant increase of the Melbourne Assessment of Unilateral Upper Limb Function. CONCLUSIONS: The parameter described here was able to show variations in performance over time and enabled a quantitative evaluation of motion abilities in a way that is reliable with respect to a well-known clinical scale.

COVID-19 y la pandemia olvidada: el seguimiento de las enfermedades neurocognitivas durante la cuarentena en Argentina / COVID-19 and the forgotten pandemic: follow-up of neurocognitive disorders during lockdown in Argentina

INTRODUCCIÓN: Varios países del mundo padecen una grave carga en sus sistemas de salud como consecuencia de la pandemia por COVID-19. Esta realidad pone en riesgo el seguimiento de patologías crónicas como las demencias. Asimismo, la atención de las posibles complicaciones neuropsiquiátricas relacionadas con el aislamiento preventivo de la población (cuarentena), que en el caso de Argentina se considera la más prolongada de Latinoamérica. El objetivo del presente trabajo es determinar la frecuencia de las distintas modalidades de consulta médica en relación con la patología neurocognitiva del paciente y las variables predictoras de consulta desde el inicio de la cuarentena. MÉTODOS: Estudio descriptivo observacional y transversal basado en la recolección de datos a través de una encuesta. RESULTADOS: Hubo 324 participantes, 165 (50,9%) de los cuales realizaron al menos una consulta médica. Frecuencia de modalidades de consulta: teléfono, 109 (33,6%); correo electrónico, 62 (19,1%); videoconsulta, 30 (9,3%); servicio de emergencias, 23 (7,1%). Predictores de consulta: Clinical Dementia Rating ≥ 1 (p < 0,001); diagnóstico: Alzheimer (p = 0,017). Se encontraron puntajes más altos del Inventario Neuropsiquiátrico (NPI) en el grupo que ha realizado consultas médicas (p < 0,001). Dicha diferencia no fue observada en el puntaje de la escala de carga del cuidador (Zarit). CONCLUSIÓN: Evidenciamos alta prevalencia de trastornos conductuales en pacientes y de sobrecarga en cuidadores durante la cuarentena. Solamente el 50% accedió a una consulta médica (52,7% por modalidad telefónica y correo electrónico). Es necesario extremar los cuidados en personas con demencia, garantizando el seguimiento de su patología

INTRODUCTION: Health systems in numerous countries around the world are suffering a serious burden as a consequence of the COVID-19 pandemic. As a result of this situation, the follow-up of such chronic diseases as dementia may be at risk. Similarly, neuropsychiatric complications related to lockdown measures may also be neglected; Argentina's lockdown has been the longest implemented in Latin America. This study aims to determine the frequency of the different types of medical consultations for neurocognitive disorders and the predictors for requiring consultation since the beginning of the lockdown. METHODS: We performed a descriptive, observational, cross-sectional study based on data collected through an online survey. RESULTS: Data were collected on 324 participants, with 165 (50.9%) having had at least one medical consultation. Consultations were held by telephone in 109 cases (33.6%), by e-mail in 62 (19.1%), by video conference in 30 (9.3%), and at the emergency department in 23 (7.1%). Predictors of requiring consultation were Clinical Dementia Rating scores ≥1 (P < .001) and diagnosis of Alzheimer disease (P = .017). Higher Neuropsychiatric Inventory scores were found in the group of respondents who did require medical consultation (P < .001), but no significant differences were found between groups for Zarit Burden Interview scores. CONCLUSION: We identified a high prevalence of behavioural disorders and caregiver burden during lockdown. Nevertheless, only 50% of respondents had sought medical consultation (by telephone or email in 52.7% of cases). Care of people with dementia must be emphasised, guaranteeing follow-up of these patients

Ovarian control of pituitary hormone secretion in early human pregnancy.

To determine the influence of ovarian relaxin on the secretion of pituitary GH and PRL in vivo, we evaluated circulating serum hormone levels in 17 pregnant patients with functional corpora lutea (group I) and compared them to levels in 10 patients with premature ovarian failure (POF; group II) who became pregnant with egg donation and did not have corpora lutea. Group II patients had exogenous hormonal support. Serum relaxin (RLX), GH, PRL, estradiol (E2), and progesterone levels were measured weekly by RIA from weeks 4-8 of pregnancy. Analysis of variance and covariance were used to determine hormonal relationships. Serum RLX was present in the natural pregnancy group, with a mean of 1.94 micrograms/L over the study period. Serum RLX was undetectable in the POF patients (less than 0.16 micrograms/L). No significant difference in PRL or progesterone levels between the two groups was noted. E2 levels showed an upward trend in both groups with time and were significantly higher in patients of the POF group than in group I women (P = 0.001). GH levels were significantly higher in the natural cycle patients (P = 0.02) despite lower E2 levels. These data provide additional support for the concept that RLX production in early pregnancy originates from the corpus luteum. They suggest that a luteal product, probably RLX, stimulates GH secretion in early pregnancy. This is a previously undescribed role for RLX in pituitary physiology during human pregnancy.

Failure of hydrocortisone to alter acutely antipyrine disposition.

The disposition of intravenously administered antipyrine in single doses of 40 mg/kg was studied in 3 dogs at 7:00 A.M. and 3 wk later at 7:00 P.M. Our purpose was to determine whether hydrocortisone differentially affected antipyrine disposition according to a circadian pattern. After each intravenous dose of antipyrine, saline was infused for 3 hr followed by intravenous hydrocortisone (2 mg/15 kg loading dose; 2 mg/15 mg/hr infusion for 3 hr). This regimen of hydrocortisone failed at either 7:00 A.M. or 7:00 P.M. to alter acutely antipyrine decay curves. Furthermore, in 4 normal male volunteers, no inflection in the salivary antipyrine decay curve occurred when hydrocortisone was injected 8 hr after antipyrine. In the human volunteers an intravenous injection of 3 mg was followed immediately by an additional 6 hr of continuous hydrocortisone infusion at 3 mg/hr. These experiments show that hydrocortisone alters the pharmacokinetics of previously administered antipyrine in neither dogs nor man.

Language acquisition in special populations: a comparison between Down and Williams syndromes.

To investigate the relationship between language acquisition and cognition, we evaluated linguistic abilities in 12 Italian-speaking children with Williams syndrome (WS) and 12 with Down syndrome (DS) of comparable global cognitive level. Another control group included 12 typically developing (TD) children, matched for mental age. Linguistic measures included a parent questionnaire to assess vocabulary, a verbal comprehension test, a sentence repetition test and MLU calculated on spontaneous production. No dissociation was evident between lexical and cognitive abilities, but specific morphosyntactic difficulties emerged both in comprehension and production in children with DS. Individuals with WS, albeit less compromised than DS, also had difficulty in the phrase repetition task and, particularly, using content words. Our results demonstrate that the linguistic abilities of infants with WS are not above their cognitive level and that language development in these special populations is not only delayed, but follows a different developmental trajectory.

Massive air embolism during cardiopulmonary bypass: successful treatment with immediate hypothermia and circulatory support.

Two patients experienced an episode of massive air embolism during extracorporeal circulation. Several emergency measures were taken. (1) The roller pump was reversed to take out air from the aorta. (2) The circuit was disconnected and recirculated to eliminate air bubbles. (3) Perfusion was restarted and the patient cooled to 24 degrees C for 40 minutes. (4) Pentothal (thiopental), steroids, and assisted ventilation were administered. The outcome was favorable in both patients, and there were no neurological sequelae. Immediate cooling and prolonged circulation seem to be a satisfactory approach to this problem.