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[Features of the surgical treatment and immediate postoperative period of patients in the acute period of rupture of arterial aneurysms of the cerebral vessels].

The authors analyse the course of the immediate postoperative period in 27 patients with ruptured arterial aneurysms of the cerebral vessels. The dynamics of the local cerebral blood flow and electric resistance of the brain matter were examined for a comprehensive study of changes in cerebral circulation and metabolism. Intracranial pressure (ventricular and subdural) and mechanical resistance of the brain matter were measured with the M-34 mingograph. Such combination of the examination methods and the findings of neurological examination made it possible to study over time the pathological processes which are interconnected (circulation-metabolism-edema and swelling of the brain) and determine the course of the postoperative period. A dependence between the preoperative condition of patients and the course of the immediate postoperative period was revealed, adequate methods for correction of the pathological reactions are suggested, and the specific features of a complex clinico-physiological control in this category of patients and the informativeness of the different methods of examination are discussed.

Brain Edema↗

[Differences in the perception of periodic and non-periodic visual stimuli in rhesus macaques].

Differences in perception of periodic and non-periodic visual stimuli were studied in rhesus monkeys during elaboration of an instrumental reflex. In the process of learning selectivity was formed (within the frequency band of 0.5 = 1 octave) for each spatial frequency used as positive stimulus. The selectivity to a definite bar width was less expressed, and a more prolonged learning was needed for its formation. There was no complete transfer from the positive grid frequencies to stimuli consisting of one or two bars with a width equal to a half-period of these frequencies. The distributions of choices acquired in the process of differentiation of vertical stimuli were preserved when their orientation was changed to the horizontal one for bars of definite width. This fact points to a complete transfer of this selectivity, while its considerable widening for spatial frequencies testifies to the absence of complete transfer of frequency selectivity.

Animals↗

Is the intra-uterine period really a critical period for the development of adiposity?

OBJECTIVE: The intra-uterine environment may be a critical period for the development of adiposity. Alternatively, most of the co-variance of relative weight from birth to adulthood may be genetic in origin. This study tested whether birth weight 'tracks' into adulthood, independent of genetic factors. DESIGN: Observational twin study. Birth weights and gestational ages from birth records of 8040 twins from the Minnesota Twin Registry including 699 monozygotic (MZ) male pairs, 609 dizygotic (DZ) male pairs, 939 MZ female pairs, 880 DZ female pairs, and 893 opposite sex DZ pairs ages (yrs) 28 to 52 (Mean = 40.3; s.d. = 6.2) were compared to self-reported adult height and weight. RESULTS: The correlation of birth weight with adult height was 0.236, with adult weight 0.188, and with adult body mass index 0.078 (all P-values < 0.0005). To test if this tracking was independent of genetic influences, we analyzed intra-pair differences for MZ twins. If differences in birth weight between members of a MZ twin pair correlate with adult relative weight, this association cannot be attributed to genetic influences. The correlation of intra-pair differences in birth weight with intra-pair differences in adult height was 0.316 (P < 0.0005), with adult weight 0.136 (P < 0.0005), and with adult BMI 0.026 (P = 0.331). Results were unchanged when multivariate regression modeling was employed. CONCLUSION: These data suggest that the intra-uterine environmental influences on birth weight have an enduring impact on adult height but not on adult relative weight. This suggests that the intra-uterine period is a critical period for the development of height but not for adiposity.

Adipose Tissue↗

[Poisonings due to analgesics during a period of 14 years in Denmark--a registry study of the period 1979-1992].

The study describes consumption of and poisoning by analgesic drugs in Denmark during the period 1979-1992. During this period, fatal poisonings from analgesics almost doubled to 200 deaths per year (40% of all drug related deaths in Denmark). The annual consumption of opioids increased at the beginning of the period, but during 1985-1992 it was relatively constant at 20 million defined daily doses (DDD) and associated with 600 hospital admissions and 150-170 deaths due to poisoning per year. Within the opioid group dextropropoxyphene consumption and poisonings decreased following a National Board of Health initiative in 1985-1987. As for the weak analgesics, consisting mainly of paracetamol or salicylates, the total consumption increased gradually and reached 145 million DDD in 1992, corresponding to 160 tablets per inhabitant per year. This consumption was associated with approximately 750 hospital admissions and 40 deaths due to poisoning. As judged from the mortality per dose the weak analgesics are 20-30 times safer than the opioids.

Analgesics↗

Periodic health examination, 1995 update: 3. Screening for visual problems among elderly patients. Canadian Task Force on the Periodic Health Examination.

OBJECTIVE: To provide recommendations to family physicians for screening elderly patients (over 65 years of age) for visual impairment and its common clinical causes. OPTIONS: Visual acuity screening with Snellen sight chart, funduscopy, retinal photography, tonometry and perimetry. OUTCOMES: Delay or prevention of visual deterioration or blindness. EVIDENCE: A MEDLINE search for relevant articles published between January 1986 and December 1993 was undertaken, the bibliographies of the articles were scrutinized for additional articles, and experts were consulted. The highest available level of evidence was used in making recommendations. VALUES: The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examination were used. Preservation of vision was given the highest value in accordance with other guidelines regarding eyesight. BENEFITS, HARMS AND COSTS: Potential benefits are to maintain or improve visual acuity. Potential for harm to patients is minimal. Limited data are available on costs. RECOMMENDATIONS: There is fair evidence to include in the periodic health examination visual acuity testing with a Snellen sight chart and funduscopy or retinal photography in elderly patients with diabetes of at least 5 years' duration (grade B recommendation). The place of funduscopy in the detection of age-related macular degeneration and glaucomatous changes is controversial. For patients at high risk for glaucoma (positive family history, black race, severe myopia or diabetes) it would be prudent to have a periodic assessment by an ophthalmologist. VALIDATION: Recommendations differ from those of the American Academy of Ophthalmology and the American Optometric Association. Recommendations for glaucoma screening are similar to those of the US Preventive Services Task Force. Present recommendations have been reviewed by experts in ophthalmology and optometry. SPONSOR: These guidelines were developed and endorsed by the task force, which is funded by Health Canada and the National Health Research and Development Program. The principal author (C.P.) was supported in part by the Educational Centre for Aging and Health, McMaster University, Hamilton, Ont.

Aged↗

Periodic health examination, 1996 update: 2. Screening for chlamydial infections. Canadian Task Force on the Periodic Health Examination.

OBJECTIVE: To update the 1984 recommendations of the Canadian Task Force on the Periodic Health Examination on the routine screening of asymptomatic patients for infection with Chlamydia trachomatis. OPTIONS: Screening, with the use of culture or nonculture tests, of the general population, of certain high-risk groups or of all pregnant women; or no routine screening. OUTCOMES: Rates of asymptomatic and symptomatic chlamydial infection, perinatal complications, longterm complications of infection (i.e., pelvic inflammatory disease, infertility and ectopic pregnancy), coinfection with other sexually transmitted diseases, disease spread, hospital care, complications of therapy and costs of infection and of screening. EVIDENCE: Search of MEDLINE for articles published between Jan. 1, 1983, and Dec. 31, 1995, with the use of the major MeSH heading "chlamydial infections," references from recent review articles and recommendation by other organizations. VALUES: The evidence-based methods of the Canadian Task Force on the Periodic Health Examination were used. Advice from reviewers and experts and recommendations of other organizations were taken into consideration. Prevention of symptomatic disease and decreased overall costs were given high values. BENEFITS, HARMS AND COSTS: The greatest potential benefits of screening asymptomatic patients for chlamydial infections are the prevention of complications, especially infertility and perinatal complications, and the prevention of disease spread. There is no evidence that screening of the general population for chlamydial infections leads to a reduction in complications, and screening may increase costs. However, there is evidence that annual screening of selected high-risk groups and of pregnant women during the first trimester is beneficial in preventing symptoms and reducing the overall cost resulting from infection. RECOMMENDATIONS: There is fair evidence to support screening and treatment of pregnant women during the first trimester (grade B recommendation) as well as annual screening and treatment of high-risk groups (sexually active women less than 25 years of age, men or women with new or multiple sexual partners during the preceding year, women who use nonbarrier contraceptive methods and women who have symptoms of chlamydial infection: cervical friability, mucopurulent cervical discharge or intermenstrual bleeding; grade B recommendation). There is fair evidence to exclude routine screening of the general population (grade D recommendation). VALIDATION: These recommendations are similar to those of the US Preventive Services Task Force and the US Centers for Disease Control and Prevention, Atlanta. SPONSOR: These guidelines were developed and endorsed by the Canadian Task Force on the Periodic Health Examination, which is funded by Health Canada and the National Health Canada and the National Health Research and Development Program. The principal author (H.D.D.) was supported in part by the Ontario Ministry of Health and the Canadian Infectious Diseases Society Lilly Fellowship.

Chlamydia Infections↗

[Is autonomic control of the heart rate at rest altered by detraining? A study of heart rate variability in professional soccer players after the pretraining period and after the preparatory period for competitions].

The aim of this study was to assess the influence of detraining and training on the autonomic control of heart rate (HR), using time and frequency (spectral analysis) domain components of heart rate variability. Sixteen professional football players (26.7 +/- 3.8 years; 74.9 +/- 4.1 kg; 177 +/- 6.3 cm) were analysed at the end of a 1 month holiday (detraining) and after a 6 week training period (training). HR was recorded over 15 minutes with Holter equipment. The athletes rested in a supine position, in a quiet place and all test were performed between 8 and 10 AM. The subjects were requested to refrain from meals or caffeine for 12 hours before testing. In spite of the high intensity of the training period, there was no significant change in results from detraining condition to training condition. These results can have two possible explanations: (i) the high level of cardiovascular capacity in the detraining trial originated by the recreative physical activity that the players underwent during their holidays, and/or (ii) the training period was not long enough to promote any relevant effect on the autonomic control of HR.

Adaptation, Physiological↗

Heart rate and spectral EEG changes accompanying periodic and non-periodic leg movements during sleep.

OBJECTIVE: To evaluate the changes in heart rate (HR) and EEG spectra accompanying periodic (PLM) and non-periodic leg movements (NPLM) during sleep in patients with restless legs syndrome (RLS). METHODS: Sixteen patients with RLS underwent one polysomnographic night recording; leg movements (LMs) during sleep were detected and classified as PLM or NPLM; up to 10 PLM and NPLM were chosen from NREM and REM sleep, for each patient and for each type (mono- or bilateral). EEG spectral analysis and HR were evaluated for 20s preceding and 30s following the onset of each LM. RESULTS: EEG activation preceded LMs, particularly in the delta band which increased before the other frequency bands, in NREM sleep but not in REM sleep for PLM, and in both stages for NPLM. A similar difference was seen between mono- and bilateral LMs. CONCLUSIONS: Sleep EEG, HR, and leg motor activity seems to be modulated by a complex dynamically interacting system of cortical and subcortical mechanisms, which influence each other. SIGNIFICANCE: Future studies on the clinical significance of leg motor events during sleep need to take into account events classifiable as "isolated" and to integrate the autonomic and EEG changes accompanying them.

Autonomic Nervous System↗

Neuropeptide Y rapidly reduces Period 1 and Period 2 mRNA levels in the hamster suprachiasmatic nucleus.

The mammalian suprachiasmatic nucleus (SCN) contains the main circadian clock. Neuropeptide Y (NPY) that is released from the intergeniculate leaflet of the lateral geniculate body to the SCN, acts in the SCN to advance circadian phase in the subjective day via the NPY Y2 receptor. We used semi-quantitative in situ hybridization to determine the effect of NPY on circadian clock genes, Period 1 (Per1) and Period 2 (Per2), expression in SCN slices. Addition of NPY to the brain slices in the subjective day resulted in reduction of Per1 and Per2 mRNA levels 0.5 and 2 h after treatment. NPY Y1/Y5 and Y2 agonists decreased Per1 within 0.5 h. These results suggest that NPY may induce phase shifts by mechanisms involving or resulting in reduction of Per1 and Per2 mRNA levels.

Animals↗

Restoration of circadian behavioural rhythms in a period null Drosophila mutant (per01) by mammalian period homologues mPer1 and mPer2.

BACKGROUND: Recent molecular studies suggest that mammals and Drosophila utilize similar components to generate circadian (approximately equal to 24 h) rhythms. The first identified circadian clock gene, the period (per) gene, is indispensable for behavioural rhythms in Drosophila and is represented in mammals by three orthologues, the relative roles of which are not known. In this study, we investigated the functional conservation of per by introducing the mouse mPer1 and mPer2 genes, driven by the Drosophila timeless (tim) promoter, into Drosophila melanogaster. RESULTS: Behavioural assays showed that both mPer constructs restored rhythms in per(01) flies that are otherwise arrhythmic due to a lack of endogenous per protein (PER). However, the rhythms restored by mPer2 were generally stronger and differed in periodicity from those restored by mPer1. In rhythmic transgenic flies, mPER proteins were expressed in lateral neurones and/or many cells in optic lobe. In addition, cell culture experiments indicated that the Drosophila PER partner, TIM, can form a complex with each of these two mammalian proteins. CONCLUSIONS: This study demonstrates that both mPer1 and mPer2 can function as clock components, and has implications for a functional analysis of the different per genes.

Animals↗

Relationship between overfeeding and overconditioning in the dry period and the problems of high producing dairy cows during the postparturient period.

In dairy cows, overfeeding during the dry period leads to overcondition at calving and to depression of appetite after calving. As a consequence, at calving overconditioned high-producing dairy cows inevitably go into a more severe negative energy balance (NEB) postpartum than cows that have a normal appetite. During the period of NEB, the energy requirements of the cow are satisfied by lipolysis and proteolysis. Lipolysis results in an increased concentration of non esterified fatty acids (NEFA) in the blood. In the liver, these NEFA are predominantly esterified to triacylglycerols (TAG) that are secreted in very low density lipoproteins (VLDL). In early lactation in cows with a severe NEB, the capacity of the liver to maintain the export of the TAG in the form of VLDL in balance with the hepatic TAG production is not always adequate. As a result, the excess amount of TAG accumulates in the liver, leading to fatty infiltration of the liver (hepatic lipidosis or fatty liver). The NEB and/or fatty liver postpartum are frequently associated with postparturient problems. In general, a severe NEB induces changes in biochemical, endocrinological, and metabolic pathways that are responsible for production, maintenance of health, and reproduction of the postparturient dairy cow. These changes include a decrease in blood glucose and insulin concentrations, and an increase in blood NEFA concentrations. High NEFA concentrations caused by intensive lipolysis are accompanied by impairment of the immune system, making the cows more vulnerable to infections. Metabolic diseases such as ketosis, milk fever, and displaced abomasum are related to overcondition at calving. The changes in biochemical, endocrinological, and metabolic pathways are associated with delay of the first visible signs of oestrus, an increase in the interval from calving to first ovulation, a decrease in conception rate, and a prolonged calving interval. It is possible that the increased blood NEFA concentration directly impairs ovarian function.

Animal Feed↗

Hyperkalemic periodic paralysis associated with multiple sleep onset REM periods.

A 24-year-old man with sporadic hyperkalemic periodic paralysis (HPP) presented with moderate excessive daytime sleepiness and transitory episodes of weakness which occurred during and after sleep. Multiple sleep latency test (MSLT) demonstrated the presence of five sleep onset REM periods (SOREMPs) and a sleep latency of five minutes. Treatment with a diuretic which decreases serum potassium resolved all the clinical symtomps and a new MSLT showed the absence of SOREMPs and a sleep latency of 13.5 minutes. To our knowledge, the patient herein reported is the first case that associates sleep abnormalities and multiple SOREMPs with HPP. Furthermore, the present case suggests that SOREMPs may be explained by an increased extracellular potassium conductance related to HPP.

Adult↗

Period-adding bifurcations and chaos in a periodically stimulated excitable neural relaxation oscillator.

The response of an excitable neuron to trains of electrical spikes is relevant to the understanding of the neural code. In this paper, we study a neurobiologically motivated relaxation oscillator, with appropriately identified fast and slow coordinates, that admits an explicit mathematical analysis. An application of geometric singular perturbation theory shows the existence of an attracting invariant manifold, which is used to construct the Fenichel normal form for the system. This facilitates the calculation of the response of the system to pulsatile stimulation and allows the construction of a so-called extended isochronal map. The isochronal map is shown to have a single discontinuity and be of a type that can admit three types of response: mode-locked, quasiperiodic, and chaotic. The bifurcation structure of the system is seen to be extremely rich and supports period-adding bifurcations separated by windows of both chaos and periodicity. A bifurcation analysis of the isochronal map is presented in conjunction with a description of the various routes to chaos in this system.

Biological Clocks↗

timrit Lengthens circadian period in a temperature-dependent manner through suppression of PERIOD protein cycling and nuclear localization.

A fundamental feature of circadian clocks is temperature compensation of period. The free-running period of ritsu (timrit) (a novel allele of timeless [tim]) mutants is drastically lengthened in a temperature-dependent manner. PER and TIM protein levels become lower in timrit mutants as temperature becomes higher. This mutation reduces per mRNA but not tim mRNA abundance. PER constitutively driven by the rhodopsin1 promoter is lowered in rit mutants, indicating that timrit mainly affects the per feedback loop at a posttranscriptional level. An excess of per+ gene dosage can ameliorate all rit phenotypes, including the weak nuclear localization of PER, suggesting that timrit affects circadian rhythms by reducing PER abundance and its subsequent transportation into nuclei as temperature increases.

Animals↗

Effects of excessive iodide administered in the dry period on thyroid function and health of dairy cows and their calves in the periparturient period.

Experiments were conducted in three successive years in which iodide (I) doses of 1.25, 2.5, 5.0 and 7.5 mg/kg body weight were given to 47 dairy cows during the dry period, compared with 16 control cows on basal diets of 1 ppm I. Effects on cows dosed at 1.25 and 2.5 mg I/kg (50 and 100 ppm dry feed) were not different from controls in terms of vitality of calves, changes in plasma thyroxine (T4), plasma triiodothyronine (T3), thyroxine secretion rate and 10-mo milk yields of the lactation after treatment. Cows dosed with 5 and 7.5 mg I/kg (200 and 300 ppm dry feed) averaged 272.8 d gestation, which was significantly shorter than 279.5 d for all cows on lesser I intakes. Abnormal calves at birth were 25% from the two highest I dosages vs 8% from controls plus the two lowest I dosages. Average plasma T4 and T3 decreased on the day of calving by about 30%, while plasma total I increased about 20%. Changes were greatest in cows fed high I dosages for the longest period prepartum. Plasma I and T3 of calves at birth were about three times the concentrations in their dam's plasma and plasma T4 of neonatal calves was four to five times greater than their dams. Highest dosages of I for dams tended to depress plasma T4 and T3 in neonatal calves.

Animals↗

Periodic alternating nystagmus associated with periodic alternating skew deviation.

A 34-year-old man had both periodic alternating nystagmus and periodic alternating skew deviation. Neurologic examination and cranial computed tomography supported the diagnosis of cerebellar degeneration. Pathophysiologic mechanisms of these motility disturbances are discussed briefly. To our knowledge these two unusual eye movement abnormalities have not been reported previously in the same patient.

Adult↗

Molecular analysis of the MVK and TNFRSF1A genes in patients with a clinical presentation typical of the hyperimmunoglobulinemia D with periodic fever syndrome: a low-penetrance TNFRSF1A variant in a heterozygous MVK carrier possibly influences the phenotype of hyperimmunoglobulinemia D with periodic fever syndrome or vice versa.

OBJECTIVE: To describe biochemical findings and the spectrum of mevalonate kinase (MVK) gene mutations as well as an associated TNFRSF1A low-penetrance variant in a series of patients with clinical features of the hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). METHODS: The MVK gene was sequenced in 8 children and 1 adult (including 2 siblings) fulfilling the clinical criteria for HIDS. In addition, sequencing of exons 2, 3, 4, and 6 of the TNFRSF1A gene was performed in patients with only one or no MVK mutation. Mevalonate kinase (MK) enzyme activity in leukocytes and renal excretion of mevalonic acid were also measured. RESULTS: Mutations in the coding region of the MVK gene were detected in 6 patients, and the most common mutation was V377I. Among these patients were 2 novel mutations, both of which were located in exon 6. These novel mutations resulted in the substitution of tryptophan (TGG) by a stop codon (TGA) at amino acid position 188 (W188X) and in the exchange of valine (GTG) for alanine (GCG) at amino acid position 203 (V203A). In 1 patient, a combination of one MVK (V377I) mutation and one TNFRSF1A (R92Q) mutation was present. The patient's clinical phenotype resembled a mixture of variant-type HIDS and tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Her IgD values varied between normal and slightly increased, and the MK activity was in the low-normal range, while urinary mevalonate concentrations were always normal. CONCLUSION: The genotype findings indicate that a relatively small number of genes may be involved in the clinical manifestation of HIDS, with low-penetrance TNFRSF1A variants possibly influencing the HIDS phenotype or MVK mutations contributing to TRAPS.

Adolescent↗