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Simplified method to measure respiratory-related changes in arterial pulse pressure in patients receiving mechanical ventilation.

STUDY OBJECTIVES: Measuring respiratory-related changes in arterial pulse pressure is useful to guide fluid expansion in hemodynamically compromised patients. In the absence of automation, this can be uneasy in clinical practice. The objective of this study was to test an alternative approach (expiratory pause) that should be easier to apply. DESIGN: Prospective observational study comparing two measurement methods of a biological variable. PATIENTS: Seventeen patients receiving mechanical ventilation without spontaneous respiratory activity, with an arterial indwelling catheter, exhibiting respiratory-related fluctuations in arterial pressure. SETTING: Ten-bed respiratory ICU in a 2,000-bed university hospital. INTERVENTION: Analysis of clinically gathered data without specific experimental intervention. MEASUREMENTS: Determinations of the change in arterial pulse pressure observed during ventilatory cycling (Delta Pp,dyn) ["dynamic"] and change in arterial pulse pressure observed during expiratory pauses (Delta Pp,stat) ["static"] were performed to assess respiratory mechanics, and comparison of the two sets of data (correlation, Bland and Altman, Passing and Bablok regression). RESULTS: Delta Pp,dyn and Delta Pp,stat were strongly correlated (R = 0.964; 95% confidence interval, 0.917 to 0.987; p < 0.0001), with a good level of agreement (mean difference, 0.016; lower limit of agreement, - 0.087; upper limit, 0.120) and no systematic difference. CONCLUSION: Measuring respiratory-related Delta Pp,stat provides data that seem interchangeable with Delta Pp,dyn, providing an easy means to routinely obtain this information.

Adult↗

Alterations in acetylcholinesterase and choline acetyltransferase activities and neuropeptide levels in the ventral spinal cord of the Wobbler mouse during inherited motoneuron disease.

Enzymatic assays for acetylcholine esterase (AChE) and choline acetyltransferase (ChAT) were applied to dorsal and ventral cervical spinal cord regions taken from the Wobbler mouse, a model for inherited motoneuron disease. Early in the disease, ChAT (but not AChE) activity is significantly greater compared with the control littermate specimens. The high ChAT activity correlates with the high thyrotropin releasing hormone (also leucine-enkephalin) concentrations measured in the Wobbler ventral horn early in the disease. Late in the motoneuron disease, both AChE and ChAT activities are significantly lower than in the control littermate specimens. These data correlate with the high substance P, methionine and leucine enkephalin concentrations measured in the Wobbler ventral horn late in the motoneuron disease.

Acetylcholinesterase↗

Factors influencing the pantographic tracing of mandibular border movements.

Three studies were performed to evaluate the influence of anatomic and neuromuscular factors of pantographic tracings of mandibular border movements. In the first study, the tracing of 50 patients with TMJ and/or muscular dysfunction were made, and the data correlated with the clinical and radiologic findings. In the second study, the tracing of 20 patients were compared before and after therapy. In the third study, the tracing of 20 patients were evaluated before and after a relaxation session with biofeedback. The data showed that both articular and neuromuscular factors influence the tracing pattern. Internal derangements of TMJ, as well as muscle spasm, lead to typical tracings. The neuromuscular factor can be dramatically improved by relaxation with biofeedback. Repeated pantographic tracings before and during treatment may help in diagnosis and in the evaluation of treatment.

Adolescent↗

Diversity and structure of the methanogenic community in anoxic rice paddy soil microcosms as examined by cultivation and direct 16S rRNA gene sequence retrieval.

A dual approach consisting of cultivation and molecular retrieval of partial archaeal 16S rRNA genes was carried out to characterize the diversity and structure of the methanogenic community inhabiting the anoxic bulk soil of flooded rice microcosms. The molecular approach identified four groups of known methanogens. Three environmental sequences clustered with Methanobacterium bryantii and Methanobacterium formicicum, six were closely related but not identical to those of strains of Methanosaeta concilii, two grouped with members of the genus Methanosarcina, and two were related to the methanogenic endosymbiont of Plagiopyla nasuta. The cultivation approach via most-probable-number counts with a subsample of the same soil as an inoculum yielded cell numbers of up to 10(7) per g of dry soil for the H2-CO2-utilizing methanogens and of up to 10(6) for the acetate-utilizing methanogens. Strain VeH52, isolated from the terminal positive dilution on H2-CO2, grouped within the phylogenetic radiation characterized by M. bryantii and M. formicicum and the environmental sequences of the Methanobacterium-like group. A consortium of two distinct methanogens grew in the terminal positive culture on acetate. These two organisms showed absolute 16S rRNA gene identities with environmental sequences of the novel Methanosaeta-like group and the Methanobacterium-like group. Methanosarcina spp. were identified only in the less-dilute levels of the same dilution series on acetate. These data correlate well with acetate concentrations of about 11 microM in the pore water of this rice paddy soil. These concentrations are too low for the growth of known Methanosarcina spp. but are at the acetate utilization threshold of Methanosaeta spp. Thus, our data indicated Methanosaeta spp. and Methanobacterium spp. to be the dominant methanogenic groups in the anoxic rice soil, whereas Methanosarcina spp. appeared to be less abundant.

Acetates↗

Correlation of carotid B-mode scanning with endarterectomy findings in Japanese patients.

In this study, 13 Japanese patients who underwent carotid endarterectomy with en bloc method were prospectively evaluated by high-resolution B-mode scanning. B-mode imaging was carried out 1-2 days before operation. The most suitable consecutive longitudinal planes of the carotid bifurcation were photographed (5-8 planes). The echogain was gradually changed from a lower to a higher intensity during B-mode scanning to identify the echogenicity of the atheromatous plaques. Three-dimensional reconstructions were made of the carotid plaques before performing carotid endarterectomy, and the author investigated the correlations between the echo characteristics and the histology of the resected plaques. The echogenicity of all atheromatous plaques, except for those with calcification, was lower than that of the normal medial layer of the vessel wall. The consecutive B-mode image data correlated well with the histological findings of the resected plaques in this study. In 2 out of 13 cases, it was found to be very difficult to distinguish an ulcerated plaque from a region of fresh intraplaque hemorrhage. High-resolution B-mode scanning was found to be a very useful and reliable method for identifying the detailed structure of atheromatous plaques in the cervical carotid artery.

Aged↗

Correlation of SMNt and SMNc gene copy number with age of onset and survival in spinal muscular atrophy.

Childhood-onset autosomal recessive spinal muscular atrophy (SMA) is associated with absence of the telomeric survival motor neuron gene (SMNt) in most patients, and deletion of the neuronal apoptosis inhibitory protein (NAIP) gene in the majority of severely affected patients. Analysis of SMNt has been complicated by the existence of a centromeric copy, SMNc, which is almost identical to SMNt but which can be distinguished from it by restriction enzyme analysis. In this study 143 SMA patients have been genotyped for the presence or absence of the SMNt, SMNc and NAIP genes, and the data correlated with quantifiable clinical variables. Although a significant correlation was observed between the presence or absence of the NAIP gene and the severity of the clinical phenotype in SMA patients generally, there was no difference in age of onset or survival in type I patients with the NAIP+ or NAIP- genotype. Fluorimetric PCR analysis of SMNc gene dosage in 57 patients homozygous for the absence of the SMNt gene but in whom the NAIP gene was present showed a highly significant correlation between SMNc copy number and SMA subtype, and between SMNc copy number and both age of onset and length of survival. The data provide strong statistical support for the emerging consensus that the clinical phenotype in SMA is directed primarily by the level of functional SMN protein. The lower SMNc copy number in type I patients in whom the NAIP gene is present suggests that the SMNt gene is removed by deletion in the majority of such patients, rather than by gene conversion as is the case in SMA types II and III.

Age of Onset↗

Tutorial in Biostatistics: Evaluating the impact of 'critical periods' in longitudinal studies of growth using piecewise mixed effects models.

Recent developments in modern multivariate methods provide applied researchers with the means to address many important research questions that arise in studies with repeated measures data collected on individuals over time. One such area of applied research is focused on studying change associated with some event or critical period in human development. This tutorial deals with the use of the general linear mixed model for regression analysis of correlated data with a two-piece linear function of time corresponding to the pre- and post-event trends. The model assumes a continuous outcome is linearly related to a set of explanatory variables, but allows for the trend after the event to be different from the trend before it. This task can be accomplished using a piecewise linear random effects model for longitudinal data where the response depends upon time of the event. A detailed example that examines the influence of menarche on changes in body fat accretion will be presented using data from a prospective study of 162 girls measured annually from approximately age 10 until 4 years post menarche.

Adipose Tissue↗

Prevention of platelet aggregation by dietary polyunsaturated fatty acids in the biodegradable polyurethane vascular prosthesis: an experimental model in pigs.

A 6-7 cm long degradable polyurethane vascular prosthesis was implanted in the infrarenal aorta of 25 young growing pigs, sacrificed from day 30 to 365 to study the processes of degradation and tissue growth, the characteristics of prosthetic substitutes and the incidence of thrombosis. Ten animals were used as controls and 15 were fed with cod liver oil (25 ml twice daily). Aortography performed at day 30, 60 and 90 showed 100% thrombosed implants in the controls, while in the lipid diet fed animals there was 100% patency. At graft retrieval, there were 7 patent grafts out of 9 in the cod liver oil fed animals. Laboratory tests indicated that the lipid diet rich in n-3 polyunsaturated fatty acids induces significant modifications of lipid metabolism preventing platelet aggregation. These data correlate well with findings of the morphological studies showing that all patent prostheses are lined with tissues similar to the endothelium of the native aorta with a mid layer made of circular and longitudinal smooth muscle cells well differentiated at day 180. These data show that the essential polyunsaturated fatty acid rich diet is able to prevent thrombosis of the biodegradable polyurethane vascular prosthesis. The combination of a synthetic material and the lipid diet experimental model, makes it possible to assess the long-term tissue-synthetic material interaction and the process of tissue growth.

Animals↗

Respiratory effort during obstructive sleep apnea: role of age and sleep state.

OBJECTIVE: To evaluate the patients' individual characteristics predictive of the degree of respiratory effort developed during obstructive sleep apneas (OSAs). DESIGN: Prospective consecutive sample, collection of clinical and polysomnographic data. SETTING: University teaching hospital. PATIENTS: One hundred sixteen consecutive OSA patients with clinical symptoms of OSA and more than 20 apneas per hour of sleep. MEASUREMENTS: Anthropomorphic data, daytime blood gas values, and polysomnographic data. From esophageal pressure measurements during sleep, three indexes of respiratory effort during OSAs were derived: the maximal end-apneic esophageal pressure swing (PesMax), the increase in esophageal pressure swing (deltaPes) during the apnea, and its ratio to apnea duration (RPes). RESULTS: The indexes of respiratory effort were significantly lower in rapid eye movement (REM) than in non-REM sleep (PesMax: 50.9+/-2.5 vs 39.6+/-1.9 cm H2O, p<0.001; deltaPes: 30.9+/-1.7 vs 23.4+/-1.4 cm H2O, p<0.001; RPes: 1.05+/-0.05 vs 0.53+/-0.03 cm H2O/s, p<0.001); therefore, a separate analysis was conducted in non-REM and in REM sleep. Indexes were also significantly lower in subgroups of older as compared to younger patients (PesMax: 55.6+/-3.5 vs 40.0+/-2.2 cm H2O, p<0.001; deltaPes: 34.2+/-2.3 vs 24.1+/-1.6 cm H2O, p=0.001; RPes: 1.21+/-0.08 vs 0.8+/-0.05 cm H2O/s, p<0.001). The three indexes were closely correlated with each other and only PesMax correlation data are reported. In non-REM sleep, age was the most important single independent correlate of PesMax (r=-0.37, p=0.000). In REM sleep, the apnea-related hypoxemia, apnea duration, and age were the main contributors to the variance of PesMax. CONCLUSIONS: Respiratory effort in response to upper airway occlusion in OSA patients is lower in REM than in non-REM sleep and decreases with increasing age.

Adult↗

The intrinsic radiosensitivity of cervical carcinoma: correlations with clinical data.

PURPOSE: The aims of the work were to study the intrinsic radiosensitivity of tumor biopsies from patients with cervical carcinoma and to correlate the data with information on patient age, disease stage, differentiation status, tumor volume, and tumor ploidy. METHODS AND MATERIALS: Radiosensitivity was assessed for 145 tumors in vitro as surviving fraction at 2 Gy (SF2) using a clonogenic assay. RESULTS: Although the clonogens in tumors classified as Stage I or II tended to be more radiosensitive than in Stage III or IV disease, the difference was not statistically significant (p > 0.15). There was also no significant difference in the intrinsic radiosensitivity of well, moderately, or poorly differentiated tumors or between squamous cell carcinoma and adenocarcinoma (p > 0.53). There was no correlation between patient age and tumor radiosensitivity (p = 0.49). Large volume (> or = 4 cm) disease was more radioresistant than small volume (< 4 cm) disease, but the difference was not significant (p = 0.08). Finally, diploid tumors tended to be more radioresistant than aneuploid tumors (p = 0.07). CONCLUSION: The intrinsic radiosensitivity of cervix tumors is independent of disease stage, tumor grade, and patient age. Weak trends, however, were observed of increased tumor radioresistance for large volume disease and diploid tumors, suggesting that tumor SF2 may not be a completely independent parameter.

Adenocarcinoma↗

Genotypic identification of rickettsiae and estimation of intraspecies sequence divergence for portions of two rickettsial genes.

DNA sequences from specific genes, amplified by the polymerase chain reaction technique, were used as substrata for nonisotopic restriction endonuclease fragment length polymorphism differentiation of rickettsial species and genotypes. The products amplified using a single pair of oligonucleotide primers (derived from a rickettsial citrate synthase gene sequence) and cleaved with restriction endonucleases were used to differentiate almost all recognized species of rickettsiae. A second set of primers was used for differentiation of all recognized species of closely related spotted fever group rickettsiae. The procedure circumvents many technical obstacles previously associated with identification of rickettsial species. Multiple amplified DNA digest patterns were used to estimate the intraspecies nucleotide sequence divergence for the genes coding for rickettsial citrate synthase and a large antigen-coding gene of the spotted fever group rickettsiae. The estimated relationships deduced from these genotypic data correlate reasonably well with established rickettsial taxonomic schemes.

Antigens, Bacterial↗

Agreement between a short form and the full scale as a function of the correlation between them.

Much current research considers both correlational data and data on agreement in evaluating the usefulness of short forms of Wechsler's intelligence scales. It is demonstrated that when chance is excluded and disagreements are suitably weighted, the agreement between a short form and the Full Scale is simply an approximation to the correlation between them. Thus, the correlation itself should be the primary consideration in evaluating the usefulness of a short form.

Child↗

Preliminary observations of the utility of portable NPT.

Nocturnal penile tumescence (NPT) has been utilized as an aid in the differential diagnosis of male erectile failure. The development of portable NPT monitors will broaden its applicability. Surprisingly, there are few data correlating sexual history interviews with NPT. In this study, 50 normal controls, 25 chronically ill patients with normal renal functioning, and 48 men with end-stage renal disease (ESRD) provided both detailed sexual histories and NPT tracings from portable monitors. In general, the data obtained from these two different sources of information were congruent. The presence of a sexual partner who could verify the sexual history enhanced the congruity. Portable NPT is probably useful at the very least as a screening technique in the assessment of male erectile failure.

Adult↗

Locus of the interaction among 5-fluorouracil, leucovorin, and interferon-alpha 2a in colon carcinoma cells.

Prior studies from these laboratories demonstrated 3.2-fold potentiation of 5-fluorouracil (FUra) cytotoxicity by recombinant human interferon-alpha 2a (rIFN-alpha 2a) in GC3/cl colon adenocarcinoma cells that was significantly enhanced to 14-fold when FUra was combined with rIFN-alpha 2a + a mixture of the diasteroisomers of the biologically active (6S) and inactive (6R) leucovorin or 5-formyl-H4PteGlu (LV), events that were reversible by thymidine (dThd). In GC3/clTS-c3/c3 cells, deficient in thymidylate synthase, rIFN-alpha 2a cytotoxicity was not influenced by the concentration of dThd, indicating no direct effect at the level of dThd-less stress. Direct assays of thymidylate synthase indicated no significant difference between FUra-induced accumulation of total thymidylate synthase or free or unbound thymidylate synthase in cells receiving FUra + modulators. In addition, the cytotoxic activity of CB3717, a specific quinazoline-based inhibitor of thymidylate synthase, was not potentiated by rIFN-alpha 2a. These studies suggested that thymidylate synthase was not the primary target site for rIFN-alpha 2a activity. Since data indicated that a 5-fluoropyrimidine was required in the interaction among FUra, LV, and rIFN-alpha 2a, attention was focused at the level of DNA. Both DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs) induced by FUra were significantly elevated by rIFN-alpha 2a and LV administered as single modulators and were influenced by the concentrations of both FUra and rIFN-alpha 2a. However; when FUra was combined with LV, rIFN-alpha 2a further potentiated the frequency of DNA SSBs, and data correlated with the relative cytotoxic activity of FUra-LV-rIFN-alpha 2a combinations. No effect on CB3717-induced DNA SSBs or DSBs by rIFN-alpha 2a was demonstrated. Drug exposure for 48 h was required to detect measurable differences in DNA SSB frequency among FUra-LV-rIFN-alpha 2a treatment groups and correlated with decreased clonogenic survival under these conditions. Continuous exposure to FUra (72 h) allowed shorter exposures to LV and/or rIFN-alpha 2a (48 h) to maintain maximal cytotoxicity. Shorter exposure times for FUra during continuous exposure to the modulators were less cytotoxic. Data suggest that the primary locus of the interaction among FUra, LV, and rIFN-alpha 2a lies at the level of DNA. rIFN-alpha 2a may exert its effects via enhancement of FUra base excision or incorporation into DNA, events that subsequently become influenced by thymidylate synthase inhibition and dThd-less stress and are further potentiated by LV.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

Flow birefringence of microtubules and its relation to birefringence measurements in cells.

Understanding the molecular basis of mitotic movements in living cells will require correlative experiments on intact cells, cell models, purified tubulin, and perhaps other biopolymers. Birefringence is one assay that is useful in all of these experimental situations. Heretofore, studies of birefringence changes during mitosis have lacked a quantitative basis for interpretation in terms of microtubule number and packing density. One of the aims of this work was to establish that relationship. Purified calf brain tubulin was polymerized to equilibrium and oriented in the hydrodynamic field of a microcapillary flow birefringence apparatus. The relationship between birefringence and microtubule packing density was determined by a combination of optical, electron microscopic, and biochemical methods. The data correlate surprisingly well with those obtained by others from in vitro measurements on isolated mitotic spindles. Using the flow birefringence data, the sensitivity of polarizing microscopes for detecting microtubules was examined and found to depend on microtubule packing density, object thickness, and instrumental factors that limit both the detection and measurement of weakly birefringent objects. Because of the dependence of measurement sensitivity on object thickness, a method of measuring the thickness of microtubule bundles using the dispersion of birefringence was developed. This method is capable of measuring thickness to within two or three Airy diffraction units and does not require any assumptions regarding object symmetry.

Animals↗

Indices of resective surgery effectiveness for intractable nonlesional focal epilepsy.

Among 70 patients with intractable focal epilepsy and no specific lesion, as determined by both MRI (magnetic resonance imaging) and histopathology, outcome after resective surgery was polarized: 26 (37%) became seizure free (SF), and 27 (39%) were not helped. Eighteen (42%) of 43 standard temporal resections rendered patients SF, somewhat more than eight (30%) of 27 other procedures. To seek reliable prognostic factors, the subsequent correlative data compared features of the 26 SF patients with those of the 27 not helped. Although ictal semiology guided the site of surgical resection, it and other aspects of seizure and neurologic history failed to predict surgical outcome. However, two aspects of preoperative scalp EEGs correlated with SF outcomes: (a) among 25 patients in whom >50% of clinical seizures arose from the later resected lobe and no other origins, 18 (72%) became SF compared with seven (28%) of 25 with other ictal profiles; (b) 13 (93%) of 14 temporal lobe patients whose interictal and ictal EEGs lacked features indicative of multifocal epileptogenesis became SF compared with five (33%) of 15 with such components. The considered need for subdural (SD) EEG reduced SF outcome from 18 (90%) of 20 patients without SD to eight (24%) of 33 with SD; this likely reflected an insufficient congruity of ictal semiology and interictal and ictal scalp EEG for localizing epileptogenesis. Within this SD group, >50% of clinical seizure origins from a later resected lobe increased SF outcome somewhat: from two (14%) of 14 without this attribute to six (40%) of 15 with it; 100% of such origins increased SF outcome from two (12%) of 16 to six (46%) of 13.

Adolescent↗

Contribution of magnetic resonance imaging in non-tumoral hypopituitarism in children.

BACKGROUND: Magnetic resonance imaging (MRI) is of paramount importance for evaluating the hypothalamo-pituitary axis in children. METHODS: We summarize the main points of the MRI technique, and describe the normal appearance of the hypothalamo-pituitary axis as a function of age and pubertal status. The most frequent causes of non-tumoral hypopituitarism include anterior pituitary deficiency (growth hormone deficiency may be isolated or associated with other anterior pituitary hormone deficiencies, with or without other malformations, and related to a known genetic abnormality in some cases), isolated hypogonadotropic hypogonadism and posterior pituitary deficiency with or without anterior pituitary hormone deficiency (central diabetes insipidus may be observed without tumor development). RESULTS: We describe in detail the appearance of the adenohypophysis, the pituitary stalk and the neurohypophysis, correlations with hormone deficiencies, the abnormalities that may be associated and progression over time for each condition. CONCLUSION: An accurate description of hypothalamo-pituitary axis abnormalities is necessary for accurate diagnosis and prognosis evaluation, with certain features suggestive of particular diseases and some prognostic data correlated with phenotype.

Child↗

Water availability and the survival of Salmonella typhimurium in porous systems.

The survival of Salmonella Typhimurium LT2 in randomly packed beds of glass beads, microporous silica particles and Sephadex microspheres is examined. It is shown that the decrease in the percentage cell recovery in these porous materials at reduced water content is not correlated with the global water activity as determined by conventional vapour pressure measurements but rather with the osmotic shock induced by the sudden redistribution of water and air among the microscopic pores in the matrix surrounding the cells. For this reason the bacterial survival and growth data correlates best with physical measurements, such as NMR and electrical conductivity, which are sensitive to the microscopic air-water distribution. The implications of this observation in food safety and preservation are discussed.

Food Microbiology↗