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Hemodynamics in sepsis.

Hemodynamics in sepsis change as sepsis develops. Initial hemodynamics of sepsis often are much different from later stages of sepsis, shifting from low cardiac output states to high cardiac output states. Tissue oxygenation also changes with initial mixed venous oxyhemoglobin (Svo2) or central venous oxyhemoglobin (Scvo2) levels below normal, with later stages reflecting high values. These changes occur as sepsis progresses, producing a marked disturbance in capillary flow and tissue oxygenation. Treatments for these changes in sepsis are different, making the identification of the hemodynamic state essential to optimally treat the patient. Fortunately, hemodynamic monitoring techniques are markedly improved from older techniques such as the pulmonary artery catheter. With noninvasive techniques such as esophageal and external Doppler for measuring hemodynamics, clinicians beyond the intensive care unit can make hemodynamic assessments that were not possible until just recently. This improved assessment should make it much easier to properly identify sepsis and initiate appropriate treatments in a timely manner.

Blood Flow Velocity↗

Peptic ulcer therapy with lansoprazole and Helicobacter pylori eradication.

This study investigated the relationship between the clearance of Helicobacter pylori and the healing rate of ulcers after treatment with lansoprazole. Lansoprazole 30 mg/day was administered to 124 gastric ulcer (GU) patients and 57 duodenal ulcer (DU) patients. The healing rates were 89.6% in GU and 96.5% in DU. The rate of shift to the S2 stage of healing was 33.1% in GU and 38.6% in DU. The H. pylori-positive rate was 69.7% in GU and 74.5% in DU. H. pylori clearance rates after lansoprazole treatment were 43.4% in GU and 51.2% in DU. In GU, the ulcer healing rate in the H. pylori-positive to -negative group was significantly higher than that in the group that remained H. pylori-positive, but there were no significant differences in the rate of shift to the S2 stage of ulcer healing. In DU, there were no significant differences in either the healing rates or the rates of shift to the S2 stage of ulcer healing. This suggests that the clearance of H. pylori results in a high healing rate in GU.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Palatal configuration in complete bilateral cleft lip and palate infants before and after cheiloplasty.

OBJECTIVE: The purpose of this study was to analyze the three-dimensional configuration of the premaxilla, vomer, and lateral segments in bilateral cleft lip and palate (BCLP) infants and to investigate the early changes in the configuration following one- and two-stage cheiloplasty. METHODS: This study consisted of 10 complete BCLP infants. One-stage operations were performed in five patients according to Manchester's method at 4 months of age. Two-stage operations were done for the remaining five patients using a triangular flap according to Tennison's method, at 4 and 8 months of age. Serial plaster models before and after the cheiloplasty were measured with a computer-controlled, highly accurate, contact-type measuring apparatus. Temporal changes in the configuration and form of the premaxilla were observed using an automatic superimposition method. The inclination and deviation of the vomer were evaluated using an approximation technique to a straight line with least squares. The distance between the lateral segments and a three-dimensional coordinate of the incisal point were also measured. RESULTS AND CONCLUSIONS: The following differences in palatal configuration between the one- and two-stage cheiloplasties were observed: 1) In the two-stage group, the premaxilla shifted toward the cleft edge where the cheiloplasty was performed in both first- and second-stage operations. After the two-stage operation, the premaxilla did not shift greatly, and the premaxilla in cases 4 and 5 shifted downward and toward the cleft edge of the lateral segments where the first operation was performed. Protrusion of the premaxilla remained in the two-stage group. 2) In the one-stage group, the premaxilla in case 4 descended downward and backward without twisting or bending. The premaxilla of the other patients descended downward with twisting and bending. 3) Patients in the two-stage group had a stronger tendency toward medial collapse of the lateral segments than did those in the one-stage group.

Calcium Sulfate↗

Differentiating hemorrhagic shock and organophosphate poisoning through integrated skin microbiome-metabolome signatures.

Accurate determination of cause of death and estimation of postmortem interval (PMI) are critical yet challenging tasks in forensic science, particularly in cases with rapid demise and absence of obvious morphological abnormalities. We employed an integrative multi-omics approach to characterize postmortem microbial succession and metabolic alterations on facial skin in mouse models of hemorrhagic shock (HS) and organophosphorus poisoning (OP) across three decomposition stages: bloating (2 days), active decay (8 days), and advanced decay (16 days). Metagenomic profiling revealed significantly reduced &#x3b1;-diversity in HS compared with OP throughout all stages (p&#x2009;<&#x2009;0.001), accompanied by stage-dependent compositional shifts, including early enrichment of Firmicutes in HS and Proteobacteria in OP. A total of 237 differential taxa were identified, with Providencia and Morganella predominating in OP, whereas Staphylococcus and Corynebacterium dominated bloating stage of HS. Untargeted metabolomics uncovered distinct cause-of-death-linked metabolites, notably elevated 2'-deoxycytidine-5'-diphosphate in early OP and persistent cholic acid/cholate accumulation in HS at later PMI. Functional analysis highlighted histidine and phosphate/phosphonate metabolism as key discriminatory pathways, exhibiting stage-specific oscillations and strong correlations with characteristic taxa. These findings demonstrate that skin-based metagenomic-metabolomic integration provides robust, mechanistically informed biomarkers for both PMI estimation and cause-of-death differentiation, offering a minimally invasive and temporally dynamic tool for forensic investigations.

Animals↗

Effects of bretazenil vs. zolpidem and placebo on experimentally induced sleep disturbance in healthy volunteers.

The effects of bretazenil 0.25 and 0.5 mg, a partial agonist at the benzodiazepine receptor, on sleep electroencephalogram (EEG), subjective sleep quality and morning psychomotor performance were compared to zolpidem 10 mg and placebo using noise as an experimental sleep disturbing factor in a single dose, double-blind, crossover study. Twelve healthy volunteers were subjected to prerecorded traffic noise with a mean sound level of 52 dB(A) during eight hours in bed. Significant effects of noise were found on sleep electroencephalogram (EEG) parameters (rapid eye movement [REM] sleep, stage 2 sleep and number of arousals), and subjective sleep quality assessments, but not on psychomotor performance (choice reaction time, digit span memory, and symbol digit substitution). Both drugs reduced the number of shifts between sleep stages and the number of arousals and increased REM sleep latency. Only after 0.5 mg bretazenil, stage 2 sleep increased and REM sleep decreased. Both doses of bretazenil significantly affected performance in the symbol digit substitution test. Sleep quality improved under drug treatments compared to placebo. The results suggest that experimental sleep disturbance can be a valuable tool in the investigation of potential sleep promoting compounds.

Adult↗

Breast cancer in Florida women. Incidence and stage at diagnosis.

Using the Florida Cancer Data System, trends were examined in female breast cancer incidence and stage of diagnosis over the period 1981-1989. The crude incidence rate increased 20% due to diagnosis at local stage or in situ. Incidence rates of disease with regional or distant spread have declined. Similar trends appear in all age groups statewide and in both Hispanic and non-Hispanic whites. The shift to earlier stage at diagnosis is not seen for nonwhite women who are less likely to be diagnosed at a local stage than white women, even after controlling for the younger age distribution of nonwhite cases. For non-Hispanic whites, the percent local at diagnosis is lowest in women in urban counties. Careful breast examination and mammographic screening for asymptomatic women lead to earlier diagnosis, longer survival and even cure. While considerable progress has been made in early detection, nonwhites and some urban residents in Florida have not received the full benefit of these changes.

Adult↗

Qualitative changes in the biologic characteristics of cultured fetal rat keratinizing epidermal cells during the process of malignant transformation after benzo[a]pyrene treatment.

In vitro malignant transformation of fetal rat keratinizing epidermal cells from inbred SD rats after benzo[a]pyrene (BP) treatment was analyzed from various biologic viewpoints. BP treatment directly and indirectly effected changes in cell growth characteristics, i.e., temperature dependence for growth, in vitro keratinization, chromosome structure, and the ability to form colonies on plastic substrate, on 0.57% agar medium layer, and in 0.33% soft agar medium. BP-treated cells at 30 degrees C remained in the premalignant stages and showed shifts in chromosome structure toward the hypodiploid range and parakeratotic changes in their keratinization process. However, the cells failed to form colonies even on a plastic substrate. BP-treated cell lines that adapted to temperatures of 35 and 37.5 degrees C remained in the premalignant stages; however, they acquired the ability to form colonies on plastic substrates during subcultivation. Malignantly transformed colonies appeared in these cell lines. In vitro keratinization processes were classified into nearly normal (diffuse lamellar, focal lamellar, and parakeratotic), intermediate, and atypical subtypes (columnar, spherical, and single-cell type). Cells of atypical keratinization subtypes and some of the intermediate subtypes formed squamous cell carcinomas in syngeneic hosts. Malignantly transformed cells showed shifts in chromosome structure toward the hypotetraploid range and colony formation on the 0.57% agar medium layer. However, they failed to form colonies in 0.33% soft agar medium. With the use of changes in biologic characteristics of the cells as indicators, fetal rat keratinizing epidermal cells in culture were classified into five stages. The appearance of stage III cells seemed to be the first key step in their malignant transformation.

Animals↗

Nutrition in transition: the changing global nutrition challenge.

The rapid shift in the stage of nutrition towards a pattern of degenerative disease is accelerating in the developing world. Data from China, as shown by the China Health and Nutrition Survey, between 1989 and 1993, are illustrative of these shifts. For example, an increase from 22.8 to 66.6% in the proportion of adults consuming a higher-fat diet, rapid shifts in the structure of diet as income changes, and important price relationships are examples that are presented. There appears to reflect a basic shift in eating preferences, induced mainly by shifts in income, prices and food availability, but also by the modern food industry and the mass media. Furthermore, the remarkable shift in the occupations structure in lower-income countries from agricultural labour towards employment in manufacturing and services implies a reduction in energy expenditure. One consequence of the nutrition transition has been a decline in undernutrition accompanied by a rapid increase in obesity. There are marked differences between urban and rural eating patterns, particularly regarding the consumption of food prepared away from home. Other issues considered are the fetal origins hypothesis, whereby the metabolic efficiencies that served well in conditions of fetal undernutrition become maladaptive with overnutrition, leading to the development of abnormal lipid profiles, altered glucose and insulin metabolism and obesity. Furthermore, obesity and activity are closely linked with adult-onset diabetes. The shift towards a diet higher in fat and meat and lower in carbohydrates and fibre, together with the shift towards less onerous physical activity, carries unwanted nutritional and health effects. It is also clear that the causes of obesity must be viewed as environmental rather than personal or genetic.

China↗

The boundary between wakefulness and sleep: quantitative electroencephalographic changes during the sleep onset period.

Microstructural electroencephalographic changes during the wakefulness-sleep transition have been investigated by comparing two definitions of sleep onset: the first occurrence of stage 1 and of stage 2. Power values were calculated across a 1-28-Hz frequency range in a 1-Hz bin resolution in the sleep recordings of 26 normal subjects. Quantitative changes were assessed after averaging individual time series, aligned with respect to the first occurrence of stage 1 or of stage 2. The time course of the single-Hz activity revealed a linear increase of power in the 1-6-Hz range and a linear decrease in the 9-12- and 16-28-Hz ranges during the stage 1 transition. During the stage 2 transition, electroencephalogram power linearly increased in the 1-7- and 14-15-Hz ranges and decreased in the 18-28-Hz range, while the 8-12-Hz range fitted a second-order polynomial curve. The two 'switch' points were also compared in their ability to differentiate Hz by Hz wakefulness from sleep: a lower mean power was found after stage 1 onset in the 9-11-Hz and 20-28-Hz bins and a higher one in the 1-5-Hz bins, while a higher power was found in the 1-8-Hz and 12-16-Hz bins and a lower one in 18-28-Hz bins after stage 2 onset. The time course of three electroencephalographic frequency ranges [delta/theta/sigma (1-7 and 12-16 Hz); beta (17-28 Hz); alpha (8-11 Hz)], grouped on the basis of a principal component analysis, fitted a first-order polynomial curve for the first two ranges, and a second-order polynomial curve for the last, with a progressive decrease during wakefulness, a minimum point during stage 1, and a subsequent increase during stage 2. The uniformly increasing electroencephalographic power across the 1-16-Hz frequency range during stage 2 and the shift of functional meaning for the alpha power during stage 1 point to the start of stage 2 as a more reliable boundary between wakefulness and sleep.

Adult↗

Reconstructive management of contralateral breast cancer in patients who previously underwent unilateral breast reconstruction.

When a patient who has had unilateral breast reconstruction presents with a new cancer on the opposite side, the reconstructive management of the second breast can be unclear. This study was performed to determine whether reconstruction of the second breast is oncologically reasonable and to evaluate the reconstructive options available to these patients. Patients who had mastectomy with unilateral breast reconstruction between 1988 and 1994 and who had a minimal follow-up of 5 years from the initial breast cancer were reviewed. Of 469 patients reviewed, 18 patients (4 percent) were identified who developed contralateral breast cancer. Mean age at the initial breast cancer presentation was 43 years (range, 26 to 57 years), and mean age at presentation with contralateral breast cancer was 48 years (range, 36 to 67). The mean interval between the initial and contralateral breast cancer presentations was 5 years (range, 1 to 10 years). Mean follow-up from the time of contralateral breast cancer was 5 years (range, 1 to 9 years). In most cases, contralateral breast cancer presented at an early stage (13 of 18 patients; 72 percent), and a shift to an earlier stage at presentation of the contralateral cancer was evident compared with the initial breast cancer. Of the 18 patients who developed contralateral breast cancer, 16 (89 percent) had no evidence of disease, one was alive with disease, and one died. Reconstructive management after the initial mastectomy included 16 transverse rectus abdominis myocutaneous flaps (seven free and nine pedicled), one latissimus dorsi myocutaneous flap with implant, and one superior gluteal free flap. Surgical management of the second breast after contralateral breast cancer included breast conservation in two patients, mastectomy without reconstruction in four, and mastectomy with reconstruction in 12. Reconstruction of the second breast included one free transverse rectus abdominis myocutaneous flap, three extended latissimus dorsi flaps, two latissimus dorsi myocutaneous flaps with implants, three implants alone, two Rubens flaps, and one superior gluteal free flap. No major complications were noted after the reconstruction of the second breast. The best symmetry was obtained when similar methods and tissues were used on both sides. The incidence of contralateral breast cancer after mastectomy and unilateral breast reconstruction is low. In most cases, contralateral breast cancer presents at an earlier stage compared with the initial breast cancer, and the prognosis is good. In patients who develop a contralateral breast cancer after mastectomy and unilateral breast reconstruction, the reconstruction of the second breast after mastectomy is oncologically reasonable and should be offered to provide optimal breast symmetry and a better quality of life. The best result is obtained when similar methods and tissues are used on both sides.

Adult↗

Functions of sleep architecture and the concept of protective fields.

This article focuses on the function of human sleep architecture and, where it adjoins, on the ultradian rhythm of NREM and REM cycles. In healthy adult human sleep, NREM and REM sleep succeed each other in 90-110 min intervals. This ultradian pattern of NREM/REM succession is cyclical. Sleep architecture relates to the shifting between sleep stages of varying sleep intensity and arousal thresholds. It has been found to follow a typical but non-cyclical pattern throughout the night. In the first third of the night, light sleep alternates predominantly with slow wave sleep (SWS). As sleep progresses, the amount of SWS typically decreases and REM sleep increases. In the last third of the night, light sleep almost exclusively alternates with REM sleep. The author postulates that one function of the non-cyclical succession of sleep stages is the erection and maintenance of a protective field around the sleeper. A protective field is to be understood as an area of relative safety, minimizing the chances for an intruder to enter the field without detection. The frequent shifts between sleep phases with low and high arousal thresholds allow a periodic screening of the sleep environment for danger signals. The relevant literature on sleep architecture, ultradian rhythms and its determinants is reviewed and the implications of the concept of protective fields are discussed.

Activity Cycles↗

Changes in protein synthetic activity in early Drosophila embryos mutant for the segmentation gene Krüppel.

We have identified early embryo proteins related to the segmentation gene Krüppel by [35S]methionine pulse labelling and two-dimensional gel electrophoresis. Protein synthesis differences shared by homozygous embryos of two Krüppel alleles when compared to heterozygous and wild-type embryos are reported. The study was extended to syncytial blastoderm stages by pulse labelling and gel analysis of single embryos, using Krüppel-specific proteins from gastrula stages as molecular markers for identifying homozygous Krüppel embryos. Localized expression of interesting proteins was examined in embryo fragments. The earliest differences detected at nuclear migration stages showed unregulated synthesis in mutant embryos of two proteins that have stage specific synthesis in normal embryos. At the cellular blastoderm stage one protein was not synthesized and two proteins showed apparent shifts in isoelectric point in mutant embryos. Differences observed in older embryos included additional proteins with shifted isoelectric points and a number of qualitative and quantitative changes in protein synthesis. Five of the proteins with altered rates of synthesis in mutant embryos showed localized synthesis in normal embryos. The early effects observed are consistent with the hypothesis that the Krüppel product can be a negative or positive regulator of expression of other loci, while blastoderm and gastrula stage shifts in isoelectric point indicate that a secondary effect of Krüppel function may involve post-translational modification of proteins.

Alleles↗

Ionic shifts in myelinated nerve fibers during early stages of Wallerian degeneration.

The distribution and relative mass fraction of the diffusible ions Na, K, Cl and Ca were determined by X-ray microanalysis in the axons of rat sciatic nerve 18 h and 36 h after crush and in control nerves. The investigations were performed in freeze-dried ultrathin cryosections after shock freezing of the nerves in liquified propane. 18 h after crush, no definite alteration of the ions were found compared to the control nerves. In electron micrographs of routinely processed nerves, no ultrastructural changes were seen. 36 h after crush, two types of ionic imbalance were found, the first characterized by decreased K and slightly increased Na in the axon, the second by concurrently increasing axonal Na and Cl, accompanied, in some fibers, by accumulating Ca. These types of ionic imbalance presumably represent two stages of axolemmal permeability alteration corresponding to early structural changes of axoplasm in electron micrographs of routinely processed nerves at that time.

Animals↗

[Relation between changes in arousal level with shift of sleeping time and subsequent sleep stage pattern].

The relationship between decrease in cerebral arousal level and sleep stage pattern was examined when a cycle of 22 h-wake and 8 h-sleep was repeated four times. The subjects of the experiment were six healthy male university students. The results of the experiment showed that the period between the time when the average score of Stanford Sleepiness Scale (SSS) reached point four (a little foggy) and the rising time was gradually decreased by repetition of the 22 h-wake and 8 h-sleep cycle. It was also found that the average score for the 6th experimental day after the third cycle was significantly increased, compared with that for the 1st 22 h waking period. These results show that the cerebral arousal level, which was indicated on the scores of SSS, was gradually decreased under the present experimental wake-sleep condition. The day-to-day variation of critical fusion frequency showed a tendency similar to that of SSS, demonstrating a gradual decrease in arousal level. On the other hand, stage 4 sleep (S4) was significantly increased during sleep after the 1st 22 h waking period, compared with baseline sleep after 16 h waking time. However, a significant increase in S4 was not seen during the sleeping periods in the second to the fourth cycles of 22 h-wake and 8 h-sleep, compared with that during the sleep after the 1st 22 h waking period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Induction of granulocytic differentiation in myeloblasts by hydroquinone, a metabolite of benzene, involves the leukotriene D4 receptor.

Chronic exposure of humans to benzene (BZ), a Class I carcinogen, causes acute myelogenous leukemia, possibly via its bone marrow metabolite, hydroquinone (HQ). The ability to alter cytokine-dependent growth and differentiation in hematopoietic stem or progenitor cells appears to be a property of agents with leukemogenic potential. We have previously reported that BZ and HQ specifically stimulate granulopoiesis in mice and cause granulocytic differentiation in normal murine interleukin (IL)-3-dependent, granulocyte colony-stimulating factor (G-CSF)-inducible 32D myeloblasts. BZ induces granulocytic differentiation by upregulating the production of leukotriene D4 (LTD4), an essential intracellular mediator of G-CSF signaling. We report here that HQ (0.5-4.0 microM), as well as LTD4 (1 nM-10 microM), causes a concentration-dependent induction of granulocytic differentiation in 32D myeloblasts. Unlike LTD4, which induces terminal granulocytic differentiation, HQ undergoes a myeloperoxidase-dependent oxidation to bioreactive p-benzoquinone (BQ), which induces differentiation predominantly to the myelocyte stage. Studies with the highly specific LTD4 receptor antagonist, MK-571, suggest that BQ induces granulocytic differentiation in myeloblasts by activating the LTD4 receptor, thus obviating the requirement for LTD4. This was confirmed by the demonstration that HQ, in the presence of LTD4, shifts the stage-specific pattern of terminal differentiation induced by LTD4 to the incomplete (myelocyte) profile induced by HQ. The inability of HQ to induce a complete program of terminal granulocytic differentiation in myeloblasts, as well as its ability to compete with induction by LTD4, may have a bearing on the leukemogenic potential of BZ.

Animals↗

[Three dimensional study of the pulpal vascular changes during inflammation].

In this study, the changes of canine pulpal vascular architecture, at various stage of growth when subjected so acute and chronic inflammation were examined through a scanning electron microscope using vascular corrosive resin casts. The following results were obtained. 1. The sites of leakage of MMA resin out of the blood vessels coincided with the site where microleakage occurred, thus suggesting that resin cast method is a useful technique to study the area where vascular permeability was increased. 2. In an acute inflammation, leakage of resin out of blood vessels was mainly observed at the sites of venular network (VN) and venous capillaries, and these could be discriminated by use of the casts method. This is in accordance with the result by Tsuchiya, Magino and Palade, where they showed that vascular permeability was preferentially observed in venule and venous capillaries. 3. In pulp with a lesser number of venules during the stage of late maturation, leakage of resin was observed from those surviving venules to the bundle of main blood vessels. 4. Leakage of resin was not observed in the terminal capillary network (TCN), but in the capillary network (CN) and VN, especially just beneath the dentin, where cavity preparation with a water spray was performed. Accordingly, the generation of heat during cavity preparation was thought to be the main reason for disturbance of the pulp. 5. Severe case of suppurative and chronic ulcerative pulpitis were generated within one week after cavity preparation. The vascular architecture was characterized by a dense granular capillary network facing the ulcerative surface. 6. One week after pulpal exposure, at the stage of early maturation of pulp, the granulated blood vessels located within the exposed pulp had a tendency to shift to a pulp polyp. And the granulated blood vessels after two months showed a pulp polyp. 7. At the late maturation stage of pulp, development the pulp chamber and dentin tubules were saturated by resin cast method, suggesting the possibility of leakage out of blood vessels and the death of some odontoblasts. The pulp at this stage shifted to a gangrous pulp. 8. In conclusion, the pulpal vascularity constantly undergoes morphologic changes incidential to various condition such as growth, maturation and inflammation. Basically, vascularity of dental pulp consists of three major layers, that is TCN, CN and VN. When it comes to the maturation stage, owing to the apposition of secondary dentin, the pulp cavity will become narrow and the vasculation within it will undergo a histologic change. As a result, most of the VN disappears.(ABSTRACT TRUNCATED AT 400 WORDS)

Dental Pulp↗

The rostral level of origin of sympathetic neurons in the chick embryo, studied in tissue culture.

Groups of three consecutive somites from the first to the eleventh somite from chick embryos of stages 17-18 were grown in tissue culture for seven days. Sympathetic neurons, identified both by phase contrast microscopy and FIF histochemistry, occurred only in cultures which included the sixth, or more caudal, somites. If it is assumed that sympathetic precursor cells (neural crest cells) have not undergone a caudal shift prior to stages 17-18, and taking into account the loss of one or two rostral somites, then the anterior sympathetic ganglia are derived from neural crest caudal to the sixth or seventh somite. Thus, the vagal zone (level with somites 1-7) contributes little to the sympathetic nervous system.

Animals↗