Twenty-four-hour ambulatory blood pressure and heart rate monitoring in combat-related posttraumatic stress disorder

This study examined the cardiovascular correlates of posttraumatic stress disorder (PTSD) in Vietnam combat veterans using 24-hr ambulatory blood pressure and heart rate monitoring. Veterans with PTSD (n = 11) exhibited significantly higher heart rate and diastolic blood pressure across the 24 hr than veterans without PTSD (n = 7) (80.8 vs. 71.9 bpm, and 80.1 vs. 71.5 mm Hg, respectively). Heart rate during sleep was also significantly higher among veterans with PTSD, compared to veterans without PTSD (71.0 vs. 62.7 bpm). These results, based on a more naturalistic measurement methodology used outside the laboratory, support an association between PTSD and increased chronic cardiovascular arousal.     

Twenty-four-hour ambulatory blood pressure evaluation of antihypertensive agents

EVALUATION OF A SMOOTH BLOOD PRESSURE RESPONSE TO TREATMENT: Smooth or uniform blood pressure control is an obvious goal of antihypertensive therapy, but it is difficult to assess by the traditional clinic blood pressure measurements. Ambulatory blood pressure monitoring is therefore increasingly being used to evaluate new antihypertensive drugs and to assess the adequacy of treatment. The use of ambulatory blood pressure monitoring is based on two assumptions: that treatment must be continuously optimal, and that more frequent blood pressure measurements during treatment, particularly at different times and during various types of activity and mental states, may lead to a more accurate assessment than infrequent measurements in the clinic. When ambulatory blood pressure monitoring is used, the effect of a given antihypertensive agent or of a given antihypertensive regimen can be tested on the average blood pressure values over 24 h, or on day- or night-time values. The actual verification of the achievement of a uniform reduction of blood pressure throughout the 24-h time span can be achieved by comparing 24-h blood pressure profiles before treatment and during treatment. The so-called trough: peak ratio is generally used in an attempt at a more quantitative assessment of smooth control. Recently, we have developed the Smoothness Index, defined as the ratio between the mean hourly change in blood pressure (calculated over the 24-h period), divided by the standard deviation of these hourly changes. We have some indication that this may be a more accurate measurement of smooth blood pressure control under therapy than trough: peak ratios. TWENTY-FOUR-HOUR BLOOD PRESSURE CONTROL BY IRBESARTAN: Ambulatory blood pressure assessments are important during the clinical testing of new antihypertensive agents. Our group recently performed a multicenter study to compare the anti-hypertensive effect of three irbesartan dose regimens (75 mg once a day, 150 mg once a day, 75 mg twice a day) and placebo as measured by 24-h ambulatory blood pressure monitoring and confirmed by office blood pressure measurements. All irbesartan regimens were significantly more effective than placebo. Irbesartan at 150 mg once a day provided clinically significant and sustained blood pressure reductions over a full 24 h and had the highest trough: peak ratio and Smoothness Index. No additional benefit was observed with twice-daily dosing using irbesartan at 75 mg compared with a single daily at 150 mg. Therefore irbesartan at a single daily dose of 150 mg offers real efficacy with the potential for greater ease of administration compared with twice-daily antihypertensive therapy.     

Therapeutic efficacy of ACTH in symptomatic infantile spasms with hypsarrhythmia

The records of twenty-six infants with both symptomatic infantile spasms and classic hypsarrhythmia were reviewed to determine the efficacy of various ACTH dosages and time of initiation of therapy. Mean age of infantile spasm onset was 6.4 months. Most patients (13) had sustained perinatal hypoxic-ischemic insults. Seventeen patients (65%) had complete cessation of spasms. Between these responders and the 9 nonresponders there was no difference in duration of spasms prior to treatment (2.6 and 2.0 months) or mean ACTH dose (87.4 and 84.5 U/m2, respectively). Infants treated with high-dose ACTH (> 100 U/m2) did not have an improved response rate. The most favorable outcomes were associated with spasm onset at > 8 months of age (all of whom were responders, regardless of dose) or when treatment was started within 1 month of onset of infantile spasms with > 80 U/m2 ACTH (88% responders). Infants treated more than 2 months after onset often did not respond (57%) regardless of dose. Nonresponders with spasm onset at < 4 months of age had the worst prognoses; all had poorly controlled seizures and regressed developmentally. Although all infants in the study were neurologically abnormal, development either improved or did not deteriorate in most responder infants following spasm resolution and one-half remained seizure free. Nonresponder infants continued to have infantile spasms or other seizure types. These data suggest that ACTH is valuable in the treatment of significantly impaired infants with symptomatic infantile spasms, but the most important determinants of outcome may be age of onset and rapidity of treatment rather than dosage.     

Twenty-four-hour ambulatory oxygen desaturation and electrocardiographic recording in obstructive sleep apnea syndrome

BACKGROUND: Although nocturnal pulseoximetry is routinely performed in obstructive sleep apnea syndrome (OSAS), pulseoximetry over a 24-h period has not been studied. HYPOTHESIS: The purpose of the study was to determine whether simultaneous 24-h oxygen desaturation and electrocardiographic (ECG) recording might be used to screen for daytime sleep sequelae in patients with OSAS. METHODS: Simultaneous recording of arterial oxygen saturation (SpO2) and ECG was conducted over a 24-h period in 18 male patients with OSAS (mean age 51.3 years) who were diagnosed by standard polysomnography (PSG), and in 15 age-matched healthy subjects (mean age 52.7 years) as controls to evaluate circadian variation of these parameters. The measures of heart rate variability (HRV) were calculated from 24-h ambulatory ECGs. Seventeen patients with OSAS showed excessive daytime sleepiness (EDS). We calculated the duration in which SpO2 decreased to < 90% (duration of SpO2 < 90%). The number of apnea/hypopneas per hour (AHI) during sleep was investigated with Apnomonitors (Chest MI, Co., Tokyo) on the same day as the SpO2 recordings. RESULTS: Controls showed no episodes of oxygen desaturation. In patients with OSAS, driving (33.3% of patients with OSAS) was the most common activity in which SpO2 decreased to < 90%, followed by daytime napping (27.8%) and resting after meals (22.2%). The duration of SpO2 < 90% over a 24-h period correlated significantly with the duration levels recorded during sleep (r = 0.99, p < 0.05) and in the afternoon (r = 0.62, p < 0.05), and with the AHI (r = 0.55, p < 0.05), but not with the duration of SpO2 < 90% in the morning. The number of ventricular premature beats correlated significantly with the duration of SpO2 < 90% for a 24-h period, but not with measures of HRV. Ventricular tachycardia was found in two (11.1%) and ST-T depression in three patients (16.6%) with underlying cardiac diseases. CONCLUSION: Our results suggest that daytime sleep attacks accompanied by oxygen desaturation in patients with moderate to severe OSAS may contribute to the occurrence of traffic or cardiovascular accidents. We conclude that 24-h ambulatory recordings of SpO2 and ECG are useful for screening for daytime sleep sequelae associated with the potential risk of this pathology in OSAS during social activities.     

Developmental outcomes in children receiving resection surgery for medically intractable infantile spasms

Two-year postsurgical developmental outcomes were assessed in 24 children with infantile spasms who underwent resective surgery. The mean age of onset of infantile spasms was 12.0 weeks and the mean age at surgery was 20.8 months. Developmental outcomes were assessed using the Vineland Adaptive Behavior Scales (VABS). There was a significant increase in developmental level at 2 years postsurgery compared with presurgical levels. At 2 years postsurgery only one of the children in this series was severely retarded. The developmental outcomes of patients in the series were better than those in prior studies of symptomatic patients receiving medical treatment for infantile spasms. It is surprising that the children in the UCLA series frequently had developmental outcomes equal to and sometimes superior to other groups of children with infantile spasms, since all the UCLA patients were symptomatic, had neurologic deficits and had failed to respond to adrenocorticotrophic hormone (ACTH) and antiepileptic drugs. The 2-year postsurgery developmental outcomes were best for the children who received surgery when they were relatively young and who had the highest level of developmental attainments presurgically.     

Excitatory amino acid levels in cerebrospinal fluid of patients with infantile spasms

Infantile spasm is an age-specific epileptic encephalopathy. Long-term intellectual outcome of affected infants remains poor. The pathogenesis of infantile spasms, as well as the development of mental retardation, remains unclear. Increased excitatory amino acid neurotransmission may play a role in neuronal dysfunction and epilepsy. To study the significance of cerebrospinal fluid excitatory amino acids in infantile spasms, we determined glutamate and aspartate concentrations in cerebrospinal fluid of 13 patients with infantile spasms and 13 controls. The aspartate level in cerebrospinal fluid of the patients with infantile spasms (968 +/- 416 nmol/l) was higher than the control group (426 +/- 272 nmol/l). No difference in the mean glutamate levels was found between the patients (966 +/- 395 nmol/l) and the controls (1135 +/- 594 nmol/l). The elevated aspartate levels in cerebrospinal fluid of the patients with infantile spasms might be secondary to change in metabolism of aspartate. Aspartate is an excitatory and neurotoxic neurotransmitter, which might have a role in triggering the spasms and the development of neuronal dysfunctions in the patients with infantile spasms.     

Hemispheric lateralization of EEG in early infantile autism

Autoregressive (AR) analysis and component analysis were applied to EEGs during sleep stage 2 of normal and autistic children, since AR-coefficients of EEG characterize the autocovariance and power spectral density of EEG. In addition, as the Mahalanobis' generalized distance of the average AR coefficient vector of an EEG group at one side from that at the opposite side follows a F-distribution, the statistical inferences were carried out, whether or not there is hemispheric specialization in EEG in 21 right handed autistic children and whether there is difference between AR-spectral pattern of EEG in the autistic children and that of 28 normal children of the same age range or not. The results obtained were as follows: 1) The significant hemispheric lateralization in EEG at the significant level of 0.01 was observed in normals, whereas none of the lateralization was confirmed in autistic children. 2) The random click stimulation caused a cumulative effect on the hemispheric lateralization in the normals, but not in the autistic children. On the contrary, the effects of random flash light stimulation on hemispheric asymmetry were verified in the autistic children as well as in the normals. 3) The EEG components of autistic children were significantly different from the normal ones in frequency range of alpha-2 component wave at bilateral frontal (F1 and F2) regions and the activity of these component waves were higher in the autistic children than in the normal ones over 5 years-old. 4) These findings suggest that autistic children are not only less responsive to external stimuli, but also neurophysiologically less active in the internal regulatory mechanism.     

Temporal relationship modeling: DTP or DT immunizations and infantile spasms

The time relationship between DTP immunization and infantile spasms (IS) onset was examined using three models--association, temporal shift, and no-effect--and the case/control data from the National Childhood Encephalopathy Study (NCES). Infantile spasms cases classified as being previously abnormal (e.g., tuberous sclerosis complex patients) showed a no-effect relationship, whereas those classified as previously normal suggested a fit to the temporal shift model, i.e. no increase in number of cases but a shortening of time to onset of seizure. No data fit the association model. Analyses for vaccine complications should examine for temporal changes (i.e. temporal shift) in addition to increased risks.     

Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis

Vigabatrin has been shown to be efficient in infants with infantile spasms and tuberous sclerosis, in open studies. In order to compare vigabatrin to oral steroids, a prospective randomized multicenter study was implemented using both drugs as monotherapy in newly diagnosed patients with infantile spasms and tuberous sclerosis. Eleven infants received vigabatrin (150 mg/kg per day) and 11 hydrocortisone (15 mg/kg per day) for 1 month. Spasm free patients continued vigabatrin or progressively stopped hydrocortisone in 1 month, non-responders were crossed to the other drug for a new 2 month-period. All vigabatrin patients (11/11) were spasm-free versus 5/11 hydrocortisone infants (P < 0.01). Seven patients were crossed to vigabatrin (six for inefficacy, one for adverse events) and became also totally controlled. Mean time to disappearance of infantile spasms was 3.5 days on vigabatrin versus 13 days on hydrocortisone (P < 0.01). Five patients exhibited side effects on vigabatrin but nine on hydrocortisone (P = 0.006). Vigabatrin should therefore be considered as the first choice treatment for infantile spasms due to tuberous sclerosis.     

Adrenocorticotropic hormone therapy for infantile spasms alters pyruvate metabolism in the central nervous system

Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl compounds that are believed to stimulate the release of GH by a direct effect on the pituitary somatotrope and by stimulation of growth hormone-releasing hormone (GHRH) release and the suppression of somatostatin (SRIH) tone. Recently, the receptor for these pharmacologic agents was cloned and its expression localized to the pituitary and hypothalamus. The elucidation of an unique GHS receptor (GHS-R) suggests there is a yet to be identified endogenous ligand which could exert an important role in regulation of GH secretion. It is clearly established that GH acts to regulate its own production by feeding back at the level of the hypothalamus to downregulate GHRH and upregulate SRIH synthesis and by induction of IGF-I, which acts at the pituitary to block somatotrope responsiveness to GHRH. If the endogenous GHS/GHS-R signaling system is important in regulating GH release, it might be reasoned that changes in circulating GH concentrations would also directly or indirectly (via generation of IGF-I) modify GHS-R production. To test this hypothesis we used RT-PCR to examined pituitary and hypothalamic GHS-R mRNA levels in the spontaneous dwarf rat (SDR), an animal model characterized by the absence of GH due to a point mutation in the GH gene. In the absence of GH feedback regulation, SDR pituitary GHS-R mRNA levels were 385 +/- 61% greater (p < 0.01) than those observed in normal controls while SDR hypothalamic GHS-R mRNA levels were not significantly different from those in normal rats. Three-day subcutaneous infusion of rat GH by osmotic pump reduced SDR pituitary GHS-R mRNA levels to 55 +/- 9% of vehicle-treated controls (p < 0.05) but did not significantly alter hypothalamic GHS-R mRNA levels. To test if the changes in GHS-R mRNA levels observed following GH treatment were due to elevation of circulating IGF-I concentrations, SDRs were infused with recombinant human IGF-I. Replacement of IGF-I did not significantly alter either pituitary or hypothalamic GHS-R mRNA levels, indicating that GH acts independent of circulating IGF-I to regulate pituitary GHS-R expression in the SDR model.     

Clozapine-induced seizures and EEG abnormalities in ambulatory psychiatric patients

Being motor nerves neurinomas originating from ocular nerves are very rare, unless associated with neurofibromatosis. Authors describe two cases of oculomotor nerve i.e. third nerve, Schwann cell tumours. One of them presented as a cavernous sinus mass in a middle aged lady while the other was a middle aged man with a large cisterno-cavernous tumour. Surgical approach is discussed and the relevant literature reviewed.     

Automatic artefact detection in intraoperative EEG monitoring

The quality of intraoperative EEG monitoring is decisively influenced by automatic detection of artefacts. Undetected artefacts can mimic non-existing trends thus leading to misinterpretations of the EEG. Methods of computer-assisted artefact detection are developed and described: On the one hand the algorithms include simple threshold values of atypical parameters, on the other, they rely on situation-dependent smoothing of the EEG signal. Too strong a deviation of an artefact-relevant parameter from its smoothed value results in exclusion of the EEG segment (epoch) from further computation trends. The algorithms can clearly reduce the misclassification of highly artefact-contaminated epochs in the awake patient, without allowing anaesthesia-relevant changes to escape notice.     

Self-measurement and automatic measurement in ambulatory blood pressure monitoring

INTRODUCTION: There are strictly determined conditions under which blood pressure measurement should be done and diagnosis of hypertension made. The first BP measurement should be performed on both arms. If there is a difference, controls should be made on the side on which the pressure is higher. In older persons the Osler manoeuvre should be made in order to exclude pseudohypertension. One should be aware that in hospitalized patients the BP is lower due to the bed rest itself. SELF-MEASUREMENT OF BLOOD PRESSURE: It seems that erroneous interpretation of blood pressure fluctuation and the tendency for self-medication by patients are the most important shortcomings of blood pressure self-monitoring. According to the World Hypertension League instructions, the BP self-measurement is not recommended for patients obsessed by the disease, neurotic and anxious persons, old subjects and in those who are physically handicapped. Since the diagnosis of hypertension should be made by the physician in office conditions, in our opinion the evolution of the disease and effects of treatment should be estimated under the same conditions. BLOOD PRESSURE AMBULATORY MONITORING: Ambulatory 24-hour monitoring is of a considerable diagnostic, therapeutic and prognostic importance over the casual or self-measurement, but one should be familiar with some peculiarrities of this method. Due to the adaptation to the device, the values of BP on the first measurement, particularly during the first 5 hours are significantly higher than during the subsequent measurements. In some subjects the values during the night may be higher due to the sleeping disturbances caused by the procedure. Differentiation between dippers and non-dippers has some prognostic and therapeutic implications. White coat hypertension may be successfully established by the ambulatory measurement. There is also a correlation between the BP variations and the myocardial mass. The trough:peak ratio may contribute to the estimation of efficiency of a certain drug. There are particular indications for ambulatory BP monitoring: the differences between the office and home values of BP are considerable; borderline hypertension; hypertension without signs of the target-organ damage; transitory hypertension of hypotension; syncopal attacks; vague symptoms in hypertensive patients; atypical or nocturnal angina; evaluation of the efficiency and duration of drug action; for research purposes.     

Diagnostic utility of video EEG monitoring in paroxysmal events

A total of 89 suicide attempters were diagnosed according to the DSM-III-R, and categorized according to suicide method as 'violent' and 'non-violent' attempters, and also as those who had made previous suicide attempts ('repeaters') and those who had not ('non-repeaters'). All of the subjects completed the MNT questionnaire. Our hypothesis was that the temperament patterns would reflect specific clinical characteristics, such as psychiatric diagnoses and type of suicidal behaviour. The 'validity' (ranging from fatiguableness to a high level of psychic energy) showed a bimodal distribution, suggesting the existence of two subgroups. The subjects with adjustment disorders displayed a significantly higher mean validity than the other patients. The lowest validity scores were found in subjects with bipolar depression. Men showed significantly higher 'stability' (reflecting emotional distance from others) than women. Subjects with major depression and those who were 'violent' suicide attempters showed somewhat higher 'solidity' (unchangeability, non-impulsiveness) compared with the other groups. Female 'non-repeaters' displayed significantly lower solidity than males or other females. In general, no clear temperament patterns were detected in patients categorized according to type of suicidal behaviour. In contrast to the findings of studies of normal populations, the intercorrelations between the dimensions were considerable, especially among the men. This prompted us to perform a cluster analysis procedure in which the subjects were allocated to five clusters according to the MNT dimensions. No distinct clinical characteristics appeared in these clusters, except in the cluster with the highest validity and the lowest stability, as 54% (P = 0.014) of the patients in this cluster had an adjustment disorder diagnosis. These temperament results reflect the clinical heterogeneity of patients who attempt suicide.     

Automatic EEG analysis during long-term monitoring in the ICU

To assist in the reviewing of prolonged EEGs, we have developed an automatic EEG analysis method that can be used to compress the prolonged EEG into two pages. The proposed approach of Automatic Analysis of Segmented-EEG (AAS-EEG) consists of 4 basic steps: (1) segmentation; (2) feature extraction; (3) classification; and (4) presentation. The idea is to break down the EEG into stationary segments and extract features that can be used to classify the segments into groups of like patterns. The final step involves the presentation of the processed data in a compressed form. This is done by providing the EEGer with a representative sample from each group of EEG patterns and a compressed time profile of the complete EEG. To verify the above approach, 41 6 h EEG records were assessed for normality via the AAS-EEG and conventional EEG approaches. The difference between the overall assessment via compressed and conventional EEG was within one abnormality level 100% of the time, and within one-half level for 73.6% of the records. We demonstrated the feasibility and reliability of automatically segmenting and clustering the EEG, thus allowing the reduction of a 6 h tracing to a few representative segments and their time sequence. This should facilitate review of long recordings during monitoring in the ICU.     

EEG monitoring during carotid surgery: who should do the monitoring?

Recently, a new hematopoietic growth factor, stem cell factor, the ligand for the c-kit-proto-oncogene, has been cloned. The gene for this factor or for its receptor are deleted in two well known series of mice mutants which display pleiotropic stem cell defects. Therefore, this factor supposedly plays an important role in stem cell biology. This paper reviews some of the elegant genetic work which led to the discovery of the factor and of its receptor, the biological effects that this factor exerts in the hematopoietic system in normal individuals and in patients with Diamond-Blackfan anemia and speculates on some of its potential clinical applications.     

Clinical value of ambulatory monitoring of blood pressure]

Stable transduction of mammalian cells typically involves random integration of viral vectors by non-homologous recombination. Here we report that vectors based on adeno-associated virus (AAV) can efficiently modify homologous human chromosomal target sequences. Both integrated neomycin phosphotransferase genes and the hypoxanthine phosphoribosyltransferase gene were targeted by AAV vectors. Site-specific genetic modifications could be introduced into approximately 1% of cells, with the highest targeting rates occurring in normal human fibroblasts. These results suggest that AAV vectors could be used to introduce specific genetic changes into the genomic DNA of a wide variety of mammalian cells, including therapeutic gene targeting applications.