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PubMed1984

The classification and mechanisms of spontaneous abortion.

This classification of spontaneous abortions, based on placental rather than embryonic or fetal morphology, does not entail detailed embryological or histological techniques. It is readily adaptable to routine pathological laboratory practice. The advantages that may accrue from proper examination of spontaneous abortions are numerous and include provision of both clinical and epidemiological data pertinent to the immediate management of the aborting patient, as well as basic information that may clarify the mechanisms underlying the major complications of pregnancy which contribute to perinatal mortality in developed societies. The pathology of the placenta in groups 1 and 2 is seen as a possible indicator of the mechanisms leading to spontaneous abortions in man. The lesions are not seen in isolation but are viewed as a logical progression related to the time at which normal development ceases. The key and unifying concept in the hypothesis is the role of the villous circulation in the maintenance of normal trophoblastic function. In the earliest abortions, the villous circulation never develops, resulting in microscopic hydatidiform or hydropic change within the villus and attenuation of the trophoblast, while embryonic or fetal death following the establishment of a villous circulation results in the sequential changes characteristic of group 2 cases. Although the majority of embryonic and fetal deaths still remain unexplained, the hypothesis suggests a mechanism by which the abnormal conceptus may determine the outcome of pregnancy without invoking the concept of maternal rejection. Verification and extension of this hypothesis will require correlation of clinical, endocrinological, and morphological data. The histopathologist has failed to keep pace with advances in modern obstetrics during the last decade, particularly in the field of early pregnancy wastage, thus reinforcing the clinical opinion that morphological examination of abortions has little to offer in the clinical management of these cases. If counseling and therapy are to be based on scientific concepts rather than on empirical data, it is essential that this deficiency be rectified.

Abortion, Spontaneous↗
PubMed2006

Verification of the agreement of two dosimetric methods with radioiodine therapy in hyperthyroid patients.

The aim of this study was to verify the capability of an MIRD formula-based dosimetric method to predict radioiodine kinetics (fraction of administered iodine transferred to the thyroid, U0, and effective clearance rate, lambda(eff)) and absorbed dose after oral therapeutic 131I administration. The method is based on 123I intravenous administration and five subsequent gamma camera measured uptake values determined separately on different structures within the thyroid. Another dosimetric method based on only the 123I 24-h uptake and a fixed lambda(eff) value was also considered. Eighty-nine hyperthyroid patients (10 with Graves' disease and 79 with autonomously functioning nodules) were studied and 132 thyroidal structures were evaluated. The mean time interval between dosimetry and therapy was 20 +/- 10d. Uptake values were measured at 2, 4, 24, 48, and 120 h during dosimetry and at 2, 4, 24, 48, 96, and 168 h during therapy. The value 0.125d(-1) was chosen in the fixed-lambda(eff) method. The planned doses to the target ranged from 120 to 250 Gy depending on the type and severity of hyperthyroidism. The following significant correlations between therapeutic and dosimetric parameters were found: U0(ther)=0.88U0(dos) (r=0.97,p<0.01), lambda(eff)ther = 1.01 lambda(eff)dos (r=0.85,p<0.01), and D(estimated)= 0.85D(planned) (r=0.88, p<0.01). The percent difference between U0(ther) and U0(dos) ranged from -44 to 32% and between lambda(eff)ther and lambda(eff)dos from -32 to 48%. U0(ther) was lower than U0(dos) in 74% of cases: this can be explained by the self-stunning effect of 131I therapeutic activity that produced a dose of about 20 Gy with a maximum dose rate of 0.6 Gy/h over the initial 24-48 h. The differences, deltaD, between the estimated and the planned doses ranged from -42% (-87 Gy) to 32% (59 Gy); in 73% of cases the difference was within +/- 35 Gy. Greater discrepancies were found with the fixed-lambda(eff) method, in which deltaD ranged from -69 to 95% (-202 to 88 Gy, respectively). In hyperthyroid patients, the five uptake value dosimetric method is able to predict with a good agreement the radioiodine kinetics and the dose after the therapeutic administration in about 73% of the analyzed thyroid structures. The fixed-lambda(eff) method is less reliable.

Aged↗
PubMed2001

Verification of the semiclassical method for an electron moving in a homogeneous magnetic field.

A procedure based on the semiclassical approximation for high energy levels is developed to yield solutions to the classical equation of charge motion and to the Bargmann-Michel-Telegdi spin equation. To this end, exact solutions to the Klein-Gordon and the Dirac-Pauli equations are used. The essence of the procedure under review is that the quantum state of a charged particle in a homogeneous magnetic field is represented as a superposition of states corresponding to the neighboring energy levels. As a consequence, the expectation values of the momentum and spin operators with respect to the resulting nonstationary wave function (packet) strictly obey the classical equations of charge motion and spin precession.

Journal Article↗
PubMed2002

Calculation of the x-ray film response to heavy charged particle irradiation.

A model was developed to calculate the response of films to heavy ion irradiation as a function of particle type and energy. It is based on the local effect model and was extended to be applied to the non-homogeneous target of photographic emulsions. The calculation was performed for protons and carbon ions in the energy range from 2 to 430 MeV u(-1). The calculated film responses are in very good agreement with experimental data. Based on this model calculation a data base of film responses was set up. This enables a three-dimensional dose verification with films in the heavy ion tumour therapy project at GSI, Darmstadt.

Carbon↗
PubMed1984

A review of human physiological and performance changes associated with desynchronosis of biological rhythms.

This review discusses the effects, in the aerospace environment, of alterations in approximately 24-h periodicities (circadian rhythms) upon physiological and psychological functions and possible therapies for desynchronosis induced by such alterations. The consequences of circadian rhythm alteration resulting from shift work, transmeridian flight, or altered day lengths are known as desynchronosis, dysrhythmia, dyschrony, jet lag, or jet syndrome. Considerable attention is focused on the ability to operate jet aircraft and manned space vehicles. The importance of environmental cues, such as light-dark cycles, which influence physiological and psychological rhythms is discussed. A section on mathematical models is presented to enable selection and verification of appropriate preventive and corrective measures and to better understand the problem of dysrhythmia.

Adaptation, Physiological↗
PubMed1994

[Morphology of the neuroendocrine-immunologic network of connective tissue in rodent fetal development].

Multi-range neuro-endocrine-immunological function in regulation of body homeostasis gives reasons for establishment of peripheral morphological bonds. As a result from our study, the unit of trophic protection of pelvic connective tissue was identified in embryonal and fetal development of rodents. This unit connects blood vessels and their autonomic innervation with chromaffin cells, mast cells, and simple neurons. Nerve fibres of para-organ pelvic ganglions determine to complete. Author suggestion on integration of another connective tissue cells and erythroid cells with systemic network requires verification.

Animals↗
PubMed1997

Acute and chronic effects of temperature, and of nutritional state, on ion homeostasis and energy metabolism in teleost hepatocytes.

Short- and long-term effects of temperature on ion flux and energy turnover were studied in hepatocytes from thermally acclimated trout and roach. In trout hepatocytes K+ efflux was insensitive towards acute exposure to low temperature but was downregulated during cold acclimation of the fish so as to balance the uncompensated decreased K+ (Rb+) uptake of the cells. In contrast, both K+ (Rb+) uptake and K+ efflux of roach hepatocytes were temperature sensitive in the short term. These acute effects, however, were offset during cold acclimation by a near perfect compensation of both fluxes leading to re-establishment of ion flux homeostasis at the original level. Our findings, based on a new method permitting the simultaneous monitoring of K+ efflux and uptake in the same cell population, provide experimental verification of two of the three possible strategies, recently discussed by Cossins et al. (1995), by which the ionic steady state of fish cells may adjust to acute and chronic temperature change. By comparing hepatocytes from two groups of trout, one kept on a maintenance diet (ration I), the other fed ad libitum (ration II), we discovered striking effects of nutritional state on the absolute levels as well as on the temperature relationships of K+ uptake and protein synthetic activity. Both of these functions in the hepatocytes increased in the ration II fed as compared to the ration I fed trouts, but the increase of protein synthetic activity was greater and more uniform at the three experimental temperatures than that of K+ uptake. Moreover, protein synthetic activity proved to be considerably more temperature sensitive than K+ uptake and, in contrast to the latter, showed a compensatory response after cold acclimation.

Acclimatization↗
PubMedDate not supplied

Measurement of ascorbic acid and dehydroascorbic acid in mammalian tissue utilizing HPLC and electrochemical detection.

Reliable measurement of the reduced and oxidized forms of ascorbic acid (AA) is challenging because they are highly reactive and unstable compounds. Detection of small amounts of AA and dehydroascorbic acid (DHAA) is essential for determining the biochemical function of the vitamin. While a variety of techniques exist for measurement of AA with detection limits in the millimolar range, a need exists for highly reliable assessment of picomolar levels of AA and DHAA in tissues. The present study presents a method for measuring AA and DHAA that combines high performance liquid chromatography with the advantages and increased detection limits and selectivity available with coulometric electrochemical detection. The difference between AA and "total AA" in tissue samples gives an assessment of DHAA concentration. Verification of the reliability of the assay is by the successful linear recovery of exogenously added AA and DHAA in tissue homogenate. Optimal conditions for reducing DHAA in tissue samples include a pH of 7.2, reaction time of 10 min, reaction temperature equal to room temperature, and a 10 mM concentration of the reducing agent, beta-mercaptoethanol. AA and DHAA are measured in several mammalian tissues using the method presented.

Animals↗
PubMed1998

Evolution strategy optimization for selective pulses in NMR

We present a first set of improved selective pulses, obtained with a numerical technique similar to the one proposed by Geen and Freeman. The novelty is essentially a robust and efficient "evolution strategy" which consistently leads, in a matter of minutes, to "solutions" better than those published so far. The other two ingredients are a "cost function," which includes contributions from peak and average radiofrequency power, and some understanding of the peculiar requirements of each type of pulse. For example, good solutions for self-refocusing pulses and "negative phase excitation pulses" (which yield a maximum signal well after the end of the pulse) are found, as may have been predicted, among amplitude modulated pulses with 270 degrees tip angles. Emphasis is given to the search for solutions with low RF power for selective excitation, saturation, and inversion pulses. Experimental verification of accuracy and power requirements of the pulses has been performed with a 4.7 T Sisco imager. Copyright 1998 Academic Press.

Journal Article↗
PubMed1980

Extended hemilaryngectomy for T3 glottic carcinoma with preservation of speech and swallowing.

Total laryngectomy is often applied in the treatment of invasive squamous cell carcinomas that fix one side of the larynx. The major drawback, of course, is loss of the voice. In many instances, however, preservation of the uninvolved portion of the larynx is compatible with adequate tumor margins, and the preserved laryngeal remnant, although it cannot be reconstituted to allow breathing, can readily be used for voice. The principle involved is the creation of a valved tracheopharyngeal shunt, which functions as a neoglottis during expiration but constricts to close during swallowing. To accomplish this the recurrent laryngeal nerve and the myomucosal segment of intrinsic glottic musculature to which it is attached is preserved on the uninvolved side. The myomucosal segment is formed into a mucosal lined tube by releasing the soft tissues from the cartilage. The diameter and flaccidity of the tube is augmented by incorporating a flap of hypopharyngeal mucosa. Safe performance of this operation depends on careful preoperative evaluation and laryngoscopic verification and a close-working relationship with an interested surgical pathologist. The first 7 consecutive cases in which this management program has been applied are presented in review. The patients, ranging in age from 58 to 69 years old, had T3 grade 2 or 3 invasive squamous cell carcinoma. The average hospitalization was 13 days. The longest follow-up is 5 years. Clear surgical margins, local control of the disease, and satisfactory voice without significant aspiration have been achieved thus far in each case. The average subglottic pressures measured at the tracheotomy were 25 +/- 6 cm. of water (threshold opening) and 43 +/- 20 cm. of water (for phonation). Whether these encouraging initial results can be widely duplicated will probably depend on the care with which cases are selected. The dangers of applying this surgery to patients with extensive submucosal spread will be obvious to experienced laryngologists.

Aged↗
PubMed1998

Critical dissolution tests of oral systems based on statistically designed experiments. III. In vitro/in vivo correlation for multiple-unit capsules of paracetamol based on PLS modeling.

The main aims of the present study were to establish an in vitro/in vivo correlation for multiple-unit capsules of paracetamol by means of statistical prediction models and to investigate the effect of a number of in vitro variables on the discussion rate of paracetamol from the formulation. A fractional factorial screening design was used to investigate the effects of the variables agitation, pH, osmolality, viscosity, and the presence of bile salt on the dissolution rate of paracetamol. The effects were evaluated in two separate partial least-squares models, in which the responses were expressed as the cumulative percentage of paracetamol dissolved at specified time-points (model I) and as the shape (beta) and scale (eta) parameters according to the Weibull function (model II). It was concluded that agitation and viscosity had significant effects on the dissolution rate of paracetamol. Statistical models based on the responses from models I and II were then used to predict the in vitro conditions most closely correlated with the in vitro dissolution of paracetamol after administration of the formulation to 10 healthy volunteers. The predicted optimal in vitro conditions were similar for the two models and not too far from what is expected from the gastrointestinal tract. The experimental verification of the in vitro conditions showed that both models were equally good, and contributed to high degrees of correlation with the in vivo dissolution behavior of the formulation during 9 hr. The relationships obtained when plotting the percentage dissolved in vitro versus in vivo were y = 1.1x (r2 = 0.98) and y = 1.1x (r2 = 0.94) for models I and II, respectively. Based on these results, it is difficult to state a preference for one of the models. Finally, the use of statistical prediction models to develop critical in vitro tests is a successful approach in the establishment of associations between dissolution behavior in vitro and in vivo for oral extended-release systems.

Acetaminophen↗
PubMedDate not supplied

[Graphical registration of tongue in evaluation of the maxillo-mandibular relationship].

OBJECTIVE: The evaluation of the tongue-maxilla relationship, in interrelation with the maxilla-mandibular relationship, determined by the skeletal pattern or modified by the total dentures. MATERIAL AND METHOD: Clinical observations and verification of the tongue-maxilla relationship by a tongue-graphical registration, in edentulous patients, with Class II and Class III skeletal relationships, which had inappropriate dentures, both in vertical dimension of occlusion and maximal intercuspidation/centric relation. RESULTS: According to clinical observations and tongue-graphical registrations, there are obvious differences in the tongue-maxilla relationship, depending on the vertical and antero-posterior relations from every skeletal class and on the incorrect prosthesis; this leads to changes in denture's equilibrium, functionality, comfort and tolerance. CONCLUSIONS: The tongue-graphical registration can be used as a simple method of evaluation of the maxillo mandibular relationship, determined by the skeletal pattern or modified by dentures.

Dental Impression Technique↗
PubMed2006

KLF5 promotes cell proliferation and tumorigenesis through gene regulation and the TSU-Pr1 human bladder cancer cell line.

KLF5 is a transcription factor that plays important roles in multiple physical and pathological processes, including cell growth, cell cycle regulation, and angiogenesis. To better characterize KLF5 function in bladder carcinogenesis, we established stable TSU-Pr1 cell clones expressing different levels of KLF5. These clones were then characterized for cell growth, cell cycle progression, tumorigenesis, and alteration in gene expression. Overexpression of KLF5 promoted tumorigenesis of the TSU-Pr1 cancer cells in mice. Consistently, KLF5 increased G1 to S phase transition, which was accompanied by the upregulation of cyclin D1, phosphorylation of MAPK and Akt, and reduced protein levels for CDK inhibitors p27 and p15. Microarray analysis combined with expression verification in different cell systems identified a number of additional genes that are potentially regulated by KLF5, including HBP17, ITGA6, and RAIG1. These findings suggest that the KLF5 transcription factor plays an oncogenic role in the TSU-Pr1 bladder cancer cell line through the regulation of a subset of genes.

Animals↗
PubMed2026

De-escalation of radiotherapy in HPV-negative non-nasopharyngeal head and neck squamous cell carcinoma: a systematic review.

BACKGROUND: Definitive and postoperative radiotherapy are central components of treatment for head and neck squamous cell carcinoma (HNSCC) but are associated with significant toxicities that can impair long-term function and quality of life. De-escalation strategies, aiming to reduce treatment-related morbidity while maintaining tumor control, have attracted increasing interest. However, most research has focused on HPV-positive oropharyngeal carcinoma. Systematic evidence for HPV-negative disease remains limited. METHODS: PubMed and EMBASE were searched for prospective studies investigating radio(chemo)therapy de-escalation in HPV-negative, HPV-unspecified, or mixed non-nasopharyngeal HNSCC populations. CLINICALTRIALS: gov was searched for ongoing prospective trials. Data extraction and verification were performed independently by three investigators. RESULTS: Screening of 3156 records identified 14 published prospective studies, 10 in the definitive and four in the postoperative setting. Strategies included reduction or omission of elective nodal volumes, dose reduction, and combined approaches. Additionally, 23 ongoing prospective trials were identified. Across studies, elective nodal failure rates were consistently low (0-4.6%), with most recurrences occurring within high-dose volumes rather than de-escalated elective regions. Randomized evidence for elective nodal dose reduction is mixed: two trials maintained regional control and reduced acute toxicity, whereas another was stopped for futility. CONCLUSION: Available evidence on de-escalation in HPV-negative HNSCC is limited, derived primarily from small, heterogeneous phase II studies with mixed HPV populations. Although data are promising in selected settings, notably for elective nodal control, the randomized evidence for elective nodal dose reduction is conflicting, and further adequately designed prospective randomized trials are required.

Humans↗
PubMed2006

The facilitative effects of glucose ingestion on memory retrieval in younger and older adults: is task difficulty or task domain critical?

The ingestion of a glucose-containing drink has been shown to improve cognitive performance, particularly memory functioning. However, it remains unclear as to the extent to which task domain and task difficulty moderate the glucose enhancement effect. The aim of this research was to determine whether boosts in performance are restricted to particular classes of memory (episodic v. semantic) or to tasks of considerable cognitive load. A repeated measures (25 g glucose v. saccharin), counterbalanced, double-blind design was used with younger and older adults. Participants performed a battery of episodic (e.g. paired associate learning) and semantic memory (e.g. category verification) tasks under low and high cognitive load. Electrophysiological measures (heart rate and galvanic skin response) of arousal and mental effort were also gathered. The results indicated that whilst glucose appeared to aid episodic remembering, cognitive load did not exaggerate the facilitative effect. For semantic memory, there was little evidence to suggest that glucose can boost semantic memory retrieval even when the load was manipulated. One exception was that glucose facilitated performance during the difficult category fluency task. Regardless, the present findings are consistent with the domain-specific account in which glucose acts primarily on the hippocampal region, which is known to support episodic memory. The possible contribution of the hippocampus in semantic memory processing is also discussed.

Adult↗
PubMed2002

[TSH levels in newborn with low and very low birth weight vs rescreening for congenital hypothyroidism].

UNLABELLED: A disorder of thyroid function, as stated by various references, is very common among children with low and very low body weight. Also, the concentration of thyroid hormones in this group differs from that of neonates full term with the adequate body weight. In 1998, in southeastern Poland, a repeated screening for TSH level in blood spots on filter paper was introduced among neonates with low and very low birth-weight. The purpose of this work was the exclusion of late appearing transient hypothyroidism, as well as the verification of falsely positive results in the basic test. Newborns with low and very low birth-weight comprise nearly 5% of live births in the region. During 1998-2001, 4,445 children with body weight below 2500 g were tested. Tests for TSH level in blood on filter paper were carried out in neonates between three and six days of age and also at the end of the first month of life. TSH levels in blood on filter paper were estimated using the LIA method (Byk Sangtec Diagnostica). The results were divided into two groups: those with correct TSH, that is < 15 mIU/L, and those with a raised level 3 15 mIU/L. The repeated test confirmed the correct result in nearly 100% of the neonates, while in 20 (0.5%) showed the increase of TSH level above 15 mIU/L. TSH and fT4 monitoring followed by serum determinations during treatment showed primary hypothyroidism in 10 children and hyperthyrotropinemia in 5 cases. CONCLUSION: 1) It would appear advisable to introduce a repeated routine screening for hypothyroidism in the group of low and very low birth-weight neonates, as this permits the identification of cases with raised values requiring verification. 2) In addition, thanks to the repeated screening we avoid false negative pitfalls in low and very low birth-weight neonates, i.e. primary congenital and transient hypothyroidism.

Congenital Hypothyroidism↗
PubMed2001

Planning, computer optimization, and dosimetric verification of a segmented irradiation technique for prostate cancer.

PURPOSE: To develop and verify a multisegment technique for prostate irradiation that results in better sparing of the rectal wall compared to a conventional three-field technique, for patients with a concave-shaped planning target volume (PTV) overlapping the rectal wall. METHODS AND MATERIALS: Five patients have been selected with various degrees of overlap between PTV and rectal wall. The planned dose to the ICRU reference point is 78 Gy. The new technique consists of five beams, each having an open segment covering the entire PTV and several smaller segments in which the rectum is shielded. Segment weights are computer-optimized using an algorithm based on simulated annealing. The score function to be minimized consists of dose-volume constraints for PTV, rectal wall, and femoral heads. The resulting dose distribution is verified for each patient by using point measurements and line scans made with an ionization chamber in a water tank and by using film in a cylindrical polystyrene phantom. RESULTS: The final number of segments in the five-field technique ranges from 7 to 9 after optimization. Compared to the standard three-field technique, the maximum dose to the rectal wall decreases by approximately 3 Gy for patients with a large overlap and 1 Gy for patients with no overlap, resulting in a reduction of the normal tissue complication probability (NTCP) by a factor of 1.3 and 1.2, respectively. The mean dose to the PTV is the same for the two techniques, but the dose distribution is slightly less homogeneous with the five-field technique (Average standard deviation of five patients is 1.1 Gy and 1.7 Gy for the three-field and five-field technique, respectively). Ionization chamber measurements show that in the PTV, the calculated dose is in general within 1% of the measured dose. Outside the PTV, systematic dose deviations of up to 3% exist. Film measurements show that for the complete treatment, the position of the isodose lines in sagittal and coronal planes is calculated fairly accurately, the maximum distance between measured and calculated isodoses being 4 mm. CONCLUSIONS: We developed a relatively simple multisegment "step-and-shoot" technique that can be delivered within an acceptable time frame at the treatment machine (Extra time needed is approximately 3 minutes). The technique results in better sparing of the rectal wall compared to the conventional three-field technique. The technique can be planned and optimized relatively easily using automated procedures and a predefined score function. Dose calculation is accurate and can be verified for each patient individually.

Algorithms↗
PubMed2004

Analysis of chromatin assembled in vivo using exogenous histones in Physarum polycephalum.

Histones are involved in the regulation of almost all events within the eukaryotic cell nucleus that utilize DNA as a substrate. We have developed a novel approach for examining the function of histone proteins and specific domains of these proteins in these various nuclear processes, and in particular assembly of chromatin throughout the cell cycle. This approach exploits several unique characteristics of the slime mold Physarum polycephalum, including the natural synchrony of all (approximately 10(8)) nuclei throughout the cell cycle and the ability of this organism to take up exogenous proteins. Here, culture techniques and biochemical procedures for the incorporation of exogenous core histones into Physarum chromatin in vivo are described. The procedures for subsequent verification of the assembly of exogenous proteins into bona fide nucleosomes are also described.

Animals↗