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The validity of fetal heart rate monitoring during the second stage of labor.

Fetal blood pH, pCO2, and lactic acid were measured before and after the final period of the second stage of labor in an attempt to better understand th validity fetal heart rate (FHR) monitoring at this time. Following a classification derived from Melchior, six FHR patterns were recognized: 0, 1, 2a, 2b, 3, and 4. In the second stage of labor, until bearing-down efforts began, the fetal acid-base status did not change regardless of the type of tracing. At the time of delivery, as compared with values measured before the beginning of the final stage, the highest shift of lactic acid, coupled with the lowest pH shift, was associated with the type 3 pattern. The most rapid increases of lactic acid and pCO2 and decreases in pH were associated with type 2b patterns. Both type 3 and 2b patterns were ominous, but low Apgar scores were more frequent in type 3 because the duration of the final stage of labor was longer. Working from the mean slopes of the shifts of biologic parameters as a function of time, theoretical limits were derived and discussed for safe duration of the final stage of labor.

Adult↗

Outcomes of surveillance protocol of clinical stage I nonseminomatous germ cell tumors-is shift to risk adapted policy justified?

PURPOSE: We evaluated the potential risk factors for disease relapse in patients with clinical stage I nonseminomatous germ cell tumors treated with surveillance and reevaluated our treatment of these patients. MATERIALS AND METHODS: A total of 211 consecutive patients with clinical stage I nonseminomatous germ cell tumors treated with surveillance after orchiectomy between 1993 and 2005 were included in this retrospective study. Risk factors evaluated were presence of vascular invasion, proportion of embryonal carcinoma, age, tumor size, preoperatively increased serum alpha-fetoprotein and the absence of yolk sac component. RESULTS: Of the 211 patients 66 (31.3%) had disease relapse. Recurrence ranged from 2 to 32 months after orchiectomy (median 6). A total of 52 (78.8%) cases of relapse were diagnosed in year 1 of followup, 11 (16.7%) during year 2 and only 3 cases were diagnosed thereafter. The first evidence of relapse was most commonly the increase in serum tumor markers alone (28.8%) or in combination with other modalities (66.7%, overall 95.5%). While 40.9% of patients with more than 50% embryonal carcinoma had disease relapse, the relapse rate was 20.8% in patients with less than 50% embryonal carcinoma (p = 0.002). Relapse rates in patients with and without vascular invasion were 75.5% and 17.9%, respectively (p = 0.000). The relapse rates were 6.1% and 75.7% in patients with no risk factors (no vascular invasion and less than 50% embryonal carcinoma) and 2 risk factors (vascular invasion and more than 50% embryonal carcinoma), respectively (p < 0.001). Multivariate analysis revealed that vascular invasion was the most powerful predictor of relapse (OR 16.350, 95% CI 5.582-47.893). Disease-free and disease specific survival rates were 97.6% at a median followup of 75 months. CONCLUSIONS: In light of our results we suggest that all patients with vascular invasion should receive chemotherapy. However, patients with no risk factors and those with more than 50% embryonal carcinoma but without vascular invasion should be on surveillance after orchiectomy since the relapse rate is less than 30%. Although strict followup in the first year is justified, followup schemas may be reassessed for the frequency of radiological investigations.

Adolescent↗

[The dynamics of realization of spontaneous dominant lethal mutations during drosophila ontogenesis].

The dynamics of realization of spontaneous dominant lethal mutations (DLM) has been studied in cyclic crosses of 5 strains of Drosophila at 3 developmental stages. The frequency of the DLM realized at the embryonic stage was shown to be determined by the maternal organism. No predominant role of either parent in the realization of DLM at the larval and pupal stages was established. The total frequency of DLM realized at all developmental stages correlated with that of DLM realized at the embryonic stages and was determined by the maternal organism. The maternal effect in the determination of DLM frequency was not related to the shift in the stage of their realization. The DLM frequency at the embryonic stage may serve as a criterion of mutational process in strains since it reflects their genetical structure but its utilization for characterization of hybrid combinations is not expedient as it is mainly determined by the maternal organism.

Animals↗

Relationship between myosin heavy chain IId isoform and fibre types in soleus muscle of the rat after hindlimb suspension.

The relationship between the myosin heavy chain (HC) IId isoform and histochemically defined fibre types was investigated in the rat soleus muscle after hindlimb suspension. After 4 weeks of suspension, right and left muscles were removed and fibre type composition and total fibre number were examined by histochemical myosin adenosine triphosphatase staining sections. Myosin HC isoforms were analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. After the suspension, there was a significant decrease in the percentage of type I fibres and a concomitant increase in that of type IIa fibres. However, the total number of fibres was not affected by suspension. The synthesis of HC IId isoform, which was not found in the control, and the decrease in the ratio of slow type myosin heavy chain isoform (HC I) were observed after suspension. These results would may suggest that the change of fibre type composition was caused by a shift from type I to IIa fibres after suspension. Furthermore, it could be suggested that the synthesis of HC IId isoform occurred during the stage of type shift from type I to IIa fibres.

Animals↗

[Initial results with breast screening in the Enschede area. I. Effectiveness].

After one year, the effects of breast cancer screening in the region of Enschede were evaluated by means of seven parameters indicating the long-term health benefits. These parameters were: attendance rate, predictive value of a positive screening test, detection rate, incidence rate, tumour stage, surgical possibilities and type of surgical operations. The results were compared with figures from the national cost-effectiveness analysis. The attendance rate (79%), the predictive value (57%) and the detection rate (0.74%) were well over the national figures of 70%, 41% and 0.64%, respectively. The incidence of breast cancer in the age group 50-69 was 2.5 times higher, as expected. The tumour stage differed significantly (p less than 0.001) from the stages of regularly detected tumours; there was a shift to the lower stages (average tumour size was halved). The surgical possibilities increased significantly (p less than 0.01) and surgical operations performed were mostly less mutilating (not significant). We conclude that the screening for breast cancer in the Enschede region fulfills the criteria of efficacy. It is particularly the combination of a high predictive value and a relatively high detection rate compared with the clinical incidence in the previous years that is indicative of the efficacy. This does not mean that the results prove the long term health benefits of screening for breast cancer. They only give an indication of the future efficacy of screening. The impact on the quality of life is still an open question.

Aged↗

Biological behaviour and clinical implications of micrometastases.

BACKGROUND: The most important prognostic determinant in cancer is the identification of disseminated tumour burden (metastases). Micrometastases are microscopic (smaller than 2 mm) deposits of malignant cells that are segregated spatially from the primary tumour and depend on neovascular formation (angiogenesis) to propagate. METHODS: The electronic literature (1966 to present) on micrometastases and their implications in malignant melanoma and epithelial cancers was reviewed. RESULTS: Immunohistochemical techniques combined with serial sectioning offer the best accuracy for detection of nodal micrometastases. Molecular techniques should be reserved for blood samples or bone marrow aspirates. Detection of micrometastases in regional lymph nodes and/or bone marrow confers a poor prognosis in epithelial cancers. The concept of sentinel node biopsy combined with serial sectioning and dedicated screening for micrometastases may improve staging procedures. Strategies against angiogenesis may provide novel therapies to induce and maintain micrometastatic dormancy. CONCLUSION: The concept of micrometastases has resulted in a paradigm shift in the staging of epithelial tumours and our overall understanding of malignant processes.

Biopsy, Needle↗

Temporal regulation of the mid-prepupal gene FTZ-F1: DHR3 early late gene product is one of the plural positive regulators.

BACKGROUND: Various ecdysteroid responsive genes play important roles in insect moulting and metamorphosis. Late FTZ-F1, a member of the nuclear receptor superfamily, is a unique transcription factor which is induced by a pulse exposure of 20-hydroxyecdysone. Elucidation of the regulation mechanism of this gene during prepupal period will help our understanding of metamorphosis at a molecular level. RESULTS: Using transgenic fly lines carrying various transcription regulatory regions of the FTZ-F1 gene fused to the LacZ gene, we investigated cis-regulatory elements in the late FTZ-F1 transcription unit. The region which governs the stage-specific expression during prepupal period was narrowed down to 1.2kb, from -0.7 to +0.5kb relative to the transcription start site. Electrophoresis mobility shift assays using staged extracts and various probes within the stage-specific region allowed us to identify binding sites for DHR3, an early late gene product, around 170 and 450bp downstream of the transcription initiation site. Mutations disrupting these binding sites reduced the reporter gene expression without affecting the stage specificity. CONCLUSIONS: Our deletion and mutation studies of the cis-regulatory element of the FTZ-F1 gene suggest that the DHR3 binding sites located in the 5' non-coding region are involved in the prepupal expression of the gene. These DHR3 binding sites confer high level expression while other elements are also involved in stage-specific expression.

Animals↗

Chronotherapy of malaria: identification of drug-sensitive stage of parasite and timing of drug delivery for improved therapy.

The cyclic nature of malarial fever in conjunction with the pharmacokinetic characteristics of antimalarial drugs, call for the conception of a chrono-therapeutic approach for the treatment of the disease. An experimental murine malarial model was devised using the highly synchronous species Plasmodium vinckei petteri to test this rationale. Sub-curative doses of chloroquine were injected sub-cutaneously to mice either during the prepatent period or during patent infection. Inspection of the effect of drug applied at different stages of the parasitic cycle, revealed that medium size trophozoites (MT) were the most susceptible stage to chloroquine, while ring and young trophozoite stages were refractory to the drug. Chloroquine given during these latter stages, affected the parasites when they developed into the MT stage. Drug treatment during the MT stage phase-shifted the schizogonic cycle by 18 hours. Hence, treatment with two consecutive injections given 18 hours apart, i.e. timed to the overwhelming presence of the MT stage in the circulation, gave the best therapeutic results.

Animals↗

Ontogenetic transition of leaf physiology and anatomy from seedlings to mature trees of a rain forest pioneer tree, Macaranga gigantea.

In a field study, we compared anatomy and diurnal gas exchange and chlorophyll fluorescence in sunlit mature leaves of Macaranga gigantea (Reichb. f. and Zoll.) Muell. seedlings, saplings, an adult tree and suckers originating from stumps. We tested the hypothesis that the pattern of resource use shifts across various life stages with ontogenetic changes in leaf anatomy and physiology. Among leaves of different developmental stages, seedling leaves were the smallest and thinnest, whereas adult tree leaves were the largest and thickest, and the air space within the lamina was largest in seedling leaves and smallest in adult tree leaves. Photosynthetic nitrogen-use efficiency (PNUE) was higher in seedling and sapling leaves than in adult tree leaves. Mean PNUE in seedling leaves was 1.6 times that in adult tree leaves. Nevertheless, among the developmental stages, net photosynthetic rate (Pn) per unit leaf area was lowest in seedling leaves because they have the lowest nitrogen (N) content per unit leaf area. In situ water vapor stomatal conductance (g(s) at a given leaf-to-air vapor pressure deficit was highest in sapling leaves, suggesting that they have a high hydraulic efficiency per unit leaf area. Among developmental stages, intrinsic water-use efficiency (Pn/g(s)) and photochemical capacity of photosystem II were lowest in seedling leaves. Sapling leaves had the highest N concentration and Pn per unit dry mass and the highest g(s), indicating that the gradual transition from the seedling stage to the sapling stage is accompanied by an accumulation of N in plant bodies and the development of hydraulic systems to counteract unfavorable environmental stresses. The properties of adult tree leaves (low PNUE, high carbon:N ratio, small and dense cells and thick lamina) indicate that, during the transition from the sapling stage to the adult tree stage, the priority of resource use in leaves gradually shifts from enhancement of photosynthetic performance to defense against herbivory and mechanical damage. Leaf morphology and physiology were coordinated with the differences in resource use at each life stage.

Carbon Dioxide↗

Cognitive performance in multiple system atrophy.

The cognitive performance of a group of patients with multiple system atrophy (MSA) of striato-nigral predominance was compared with that of age and IQ matched control subjects, using three tests sensitive to frontal lobe dysfunction and a battery sensitive to memory and learning deficits in Parkinson's disease and dementia of the Alzheimer type. The MSA group showed significant deficits in all three of the tests previously shown to be sensitive to frontal lobe dysfunction. Thus, a significant proportion of patients from the MSA group failed an attentional set-shifting test, specifically at the stage when an extra-dimensional shift was required. They were also impaired in a subject-ordered test of spatial working memory. The MSA group showed deficits mostly confined to measures of speed of thinking, rather than accuracy, on the Tower of London task. These deficits were seen in the absence of consistent impairments in language or visual perception. Moreover, the MSA group showed no significant deficits in tests of spatial and pattern recognition previously shown to be sensitive to patients early in the course of probable Alzheimer's disease and only a few patients exhibited impairment on the Warrington Recognition Memory Test. There were impairments on other tests of visual memory and learning relative to matched controls, but these could not easily be related to fundamental deficits of memory or learning. Thus, on a matching-to-sample task the patients were impaired at simultaneous but not delayed matching to sample, whereas difficulties in a pattern-location learning task were more evident at its initial, easier stages. The MSA group showed no consistent evidence of intellectual deterioration as assessed from their performance on subtests of the Wechsler Adult Intelligence Scale (WAIS) and the National Adult Reading Test (NART). Consideration of individual cases showed that there was some heterogeneity in the pattern of deficits in the MSA group, with one patient showing no impairment, even in the face of considerable physical disability. The results show a distinctive pattern of cognitive deficits, unlike those previously seen using the same tests in patients with Parkinson's and Alzheimer's diseases, and suggesting a prominent frontal-lobe-like component. The implications for concepts of 'subcortical' dementia and 'fronto-striatal' cognitive dysfunction are considered.

Adult↗

A temperature-sensitive (TS) mutant of frog virus 3 (FV3) is defective in second-stage DNA replication.

It has been suggested that FV3 DNA replication occurs in two stages [R. Goorha (1982) J. Virol. 43, 519-528]. First-stage DNA synthesis is restricted to the nucleus, where the replicating DNA ranges from genome to twice genome size; second-stage DNA replication occurs exclusively in the cytoplasm, and the replicating DNA is concatameric. A temperature-sensitive mutant (ts 12488) of FV3, at a nonpermissive temperature (30 degrees), synthesized DNA in the nucleus only, and the size of the replicative complex (as determined by neutral sucrose gradient analysis) was between genome and twice genome length. These characteristics establish that at nonpermissive temperature, ts 12488 is arrested in the first stage of DNA replication. Temperature shift-down (30 degrees----25 degrees) of ts 12488-infected cells at 4 hr postinfection showed that, within 30 min of the shift, the replicative complex became very large (more than 10 times genome size). Furthermore, newly synthesized DNA was now found in the cytoplasmic fraction also. These results suggest that ts 12488, upon shift-down, enters into the second stage of DNA replication where progeny DNA is synthesized as a large concatamer. In shift-down experiments, de novo protein synthesis was not required to initiate second-stage DNA replication, strongly suggesting that the thermosensitive protein is directly involved in second-stage DNA replication. This genetic evidence establishes the previous biochemical findings of a two-stage replication scheme for FV3 DNA.

Animals↗

Intratumoral regional variations in copy number of the chromosomal part revealed by microdissection and combined ploidy and comparative genomic hybridization analyses in esophageal squamous cell carcinoma.

Intratumoral regional variations in the copy number of chromosomal material were analyzed to demonstrate the time sequence of chromosomal changes in progression of individual squamous cell carcinoma of the esophagus. We applied combined DNA ploidy and comparative genomic hybridization (CGH) analyses to multiple DNA samples extracted from microdissected, formalin-fixed, paraffin-embedded tissues, and amplified and labeled according to degenerate oligonucleotide-primed polymerase chain reaction. We examined two cases: one with a deep invasive tumor and the other with a superficial spreading tumor. We found that each sample had unique aberrations in addition to the ones common to all or some of the samples in a tumor. Based on previous studies (Okada et al., Cancer Genet Cytogenet 2000;118:99-107), we classified significant shifts of the green to red (G/R) ratio into small and large ones, which were within and beyond the range of 0.65 to 1.35, respectively. Most of the large-shift aberrations were found to be common to all or some of the samples in each case. These were thought to represent earlier events in the DNA-diploid stage, while small shifts may possibly reflect one-copy changes after tetraploidization or chromosomal instability. Based on the breakpoints and on the absolute copy numbers of altered chromosomal parts inferred from DNA ploidy and the shift size of the G/R ratio, we reconstructed the sequence of accumulation and divergence of chromosomal alterations as a dendrogram in each case. This method of temporal analysis may enable us to extract important early events from numerous aberrations screened by CGH in individual tumors.

Anatomy, Regional↗

Effect of pH shifts on radiosensitivity of human lymphocytes irradiated in the G2 stage.

Experiments were carried out using human lymphocytes in order to test the effect of pH shifts on radiosensitivity of cells irradiated in the G2 stage. In our culture conditions constant variations in medium pH over the range of 7.4-6.8 were observed as a function of incubation time after PHA stimulation; in addition the pH of the medium was adjusted in parallel cultures over the range of 5.9-8.2. Then we exposed the cultures with different pH to a treatment of X-rays delivered 2 h before fixation. The pH of the medium was found to greatly affect the yield of induced chromatid aberrations.

Cell Division↗

Developmental changes in DNAse I digestibility and RNA template activity of neuronal nuclei relative to the postnatal appearance of a short DNA repeat length.

Neurons of the rat cerebral hemispheres are known to undergo a postnatal shift to a short DNA repeat length. In the present study we report that rat neuronal nuclei are more sensitive to digestion with DNAse I when isolated at a developmental stage after the shift in neuronal DNA repeated length compared to nuclei isolated before the shift. This observation may suggest that a decondensation of neuronal chromatin accompanies the postnatal shift in DNA repeat length. We have also found that neuronal nuclei isolated after the shift to a short DNA repeat length demonstrate an increased ability to synthesize RNA in vitro.

Animals↗

Serial intraoperative magnetic resonance imaging of brain shift.

OBJECTIVE: A major shortcoming of image-guided navigational systems is the use of preoperatively acquired image data, which does not account for intraoperative changes in brain morphology. The occurrence of these surgically induced volumetric deformations ("brain shift") has been well established. Maximal measurements for surface and midline shifts have been reported. There has been no detailed analysis, however, of the changes that occur during surgery. The use of intraoperative magnetic resonance imaging provides a unique opportunity to obtain serial image data and characterize the time course of brain deformations during surgery. METHODS: The vertically open intraoperative magnetic resonance imaging system (SignaSP, 0.5 T; GE Medical Systems, Milwaukee, WI) permits access to the surgical field and allows multiple intraoperative image updates without the need to move the patient. We developed volumetric display software (the 3D Slicer) that allows quantitative analysis of the degree and direction of brain shift. For 25 patients, four or more intraoperative volumetric image acquisitions were extensively evaluated. RESULTS: Serial acquisitions allow comprehensive sequential descriptions of the direction and magnitude of intraoperative deformations. Brain shift occurs at various surgical stages and in different regions. Surface shift occurs throughout surgery and is mainly attributable to gravity. Subsurface shift occurs during resection and involves collapse of the resection cavity and intraparenchymal changes that are difficult to model. CONCLUSION: Brain shift is a continuous dynamic process that evolves differently in distinct brain regions. Therefore, only serial imaging or continuous data acquisition can provide consistently accurate image guidance. Furthermore, only serial intraoperative magnetic resonance imaging provides an accurate basis for the computational analysis of brain deformations, which might lead to an understanding and eventual simulation of brain shift for intraoperative guidance.

Adult↗

Mechanisms of moving the mind's eye: planning and execution of spatial shifts of attention.

The usefulness of attentional orienting, both in the real world and in the laboratory, depends not only on the ability to attend to objects or other inputs but also on the ability to shift attention between them. Although understanding the basic characteristics of these shifts is a critical step toward understanding the brain mechanisms that produce them, the literature remains unresolved on a very basic and potentially revealing characteristic of these shifts-namely, whether attention takes longer to shift a farther distance across the visual field. We addressed this question using a series of behavioral tasks involving the voluntary orienting of attention to locations in the visual field. The findings support a model in which attentional shifts include separate "planning" and "execution" stages and in which only the planning stage requires more time for shifts of a greater distance. These results offer resolution to the longstanding debate concerning the effect of attentional shift distance on shift time and provide insight into the fundamental mechanisms of attentional shifting.

Adolescent↗

[Effect of the eradication of Helicobacter pylori on peptic ulcer healing].

Acid suppressive therapy with H2 receptor antagonist or proton pump inhibitor can hardly shift peptic ulcers to S2 stage (white scar). As a result, judgement of ulcer healing has been made at S1 stage (red scar). However, it has been a problem that many ulcer scars relapse. Helicobacter pylori eradication therapy can prevent peptic ulcers from relapsing. The eradication therapy shifted 92% gastric ulcers from all stages to S2 stage after 24 months. We has divided S1 stage categorized by conventional endoscopy into H3-C stage (with small defect of mucosa) and S1-C stage by dye contrast method. The ulcers at H3-C stage relapse more frequently than those at S1-C stage. The acid suppressive therapy shifted only 7%, 15% gastric ulcers at H3-C stage, S1-C stage to S2-C stage after 6 months, respectedly. On the other hand, the eradication therapy shifted 56%, 65% gastric ulcers at H3-C stage, S1-C stage to S2-C stage, respectedly. It may be one reason why the eradication therapy prevents peptic ulcers from relapsing that the therapy shifts almost peptic ulcers to S2 stage.

Gastroscopy↗

Toxicities of hemoglobin solutions: in search of in-vitro and in-vivo model systems.

Several hemoglobin-based oxygen carriers (HBOCs) have been developed with a rationale focused on exploiting one or more physicochemical properties (e.g., oxygen affinity, molecular weight, viscosity, and colloid osmotic pressure) resulting from the chemical or recombinant modification of hemoglobin (Hb). Several chemically modified Hbs have reached late stages of clinical evaluation in the United States and Canada. These Hbs, in general, demonstrated mixed preclinical safety and efficacy, and reasonable safety in Phase I trials. However, as clinical development shifted into later stages, an undesirable safety and efficacy profile became clear in patient populations studied, and as a result some products were withdrawn from further clinical pursuit. Several questions still remain unanswered regarding the safety of Hb products for their proposed clinical indication(s). For example, 1) were preclinical studies predictive of clinical outcome? And, 2) were the most appropriate preclinical studies performed to predict clinical outcome? The primary objectives of this analysis are to explore prelinical safety issues associated with HBOCs and provide an overview of the in-vitro and in-vivo models employed. The methods for obtaining data to serve as a basis for discussion are compiled from a literature-based survey of safety and efficacy derived from biochemical, cellular, and whole animal assessment of HBOCs. Results from this overview of a vast body of published data may provide a means for identifying critical preclinical safety issues, which may ultimately lead to identification of potential limitations in the effective clinical use of certain HBOCs.

Animals↗