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Biomedical subjects

J Stein

Publications and source records attributed to J Stein.

At least 181 records · Page 10Linked to original sources

Iron overload following bone marrow transplantation in children: MR findings.

OBJECTIVE: The purpose of this study was to determine the incidence of post-transfusional iron overload in children after bone marrow transplantation by reviewing their magnetic resonance imaging (MR) findings. MATERIALS AND METHODS: We reviewed the abdominal MR studies of 13 children after autologous bone marrow transplantation. Nine of the children had also undergone MR prior to transplantation. Iron deposition in the liver, spleen and bone marrow was graded semi-quantitatively on both T1- and T2-weighted images. Serum ferritin levels and number of blood units given after bone marrow transplantation were recorded. RESULTS: None of the pre-transplantation MR studies revealed iron overload. After bone marrow transplantation, three children showed normal liver and spleen. Iron overload in the liver was noted in ten patients (77 %), six of whom also showed iron overload in the spleen (46 %) and five in the bone marrow (38.5 %). The degree of hepatic iron overload was correlated significantly and splenic iron overload was correlated weakly with the number of blood transfusions (P = 0.01 and P > 0.01, respectively), but neither was correlated with the serum ferritin level. CONCLUSION: Iron overload commonly accompanies bone marrow transplantation. The observed pattern of iron deposition, in which the spleen was uninvolved in 40 % of patients demonstrating iron overload, is not typical of post-transfusional hemochromatosis.

Abdomen↗

Electrocortical and heart rate response during vibroacoustic stimulation in fetal sheep.

OBJECTIVE: Our purpose was to study effects of vibroacoustic stimuli on electrocortical activity and heart rate changes in fetal sheep in utero. STUDY DESIGN: Seven chronically instrumented near-term fetal sheep were repeatedly stimulated by an electronic artificial larynx for 32 seconds during periods of rapid-eye-movement and non-rapid-eye-movement sleep. Responses to vibroacoustic stimulation were obtained by spectral analysis of the electrocorticogram (fast Fourier transform) and by assessment of changes in fetal heart rate and fetal heart rate variability. RESULTS: During non-rapid-eye-movement sleep vibroacoustic stimulation led to electrocorticogram desynchronization that consisted of a marked reduction of delta and theta band power (p < 0.05). A concomitant fetal heart rate decrease and fetal heart rate variability increase were also noted (p < 0.05). During rapid-eye-movement sleep vibroacoustic stimulation induced a significant increase in alpha and beta band power (p < 0.05) and a slight deviation in basal fetal heart rate and fetal heart rate variability (p < 0.05). CONCLUSION: Vibroacoustic stimulation of fetal sheep provokes reproducible changes in fetal electrocortical activity and heart rate patterns. These changes, which are not easily identifiable in gross polygraphic assessments of the fetal behavioral state, are indicative of fetal arousal.

Acoustic Stimulation↗

To see but not to read; the magnocellular theory of dyslexia.

Developmental dyslexics often complain that small letters appear to blur and move around when they are trying to read. Anatomical, electrophysiological, psychophysical and brain-imaging studies have all contributed to elucidating the functional organization of these and other visual confusions. They emerge not from damage to a single visual relay but from abnormalities of the magnocellular component of the visual system, which is specialized for processing fast temporal information. The m-stream culminates in the posterior parietal cortex, which plays an important role in guiding visual attention. The evidence is consistent with an increasingly sophisticated account of dyslexia that does not single out either phonological, or visual or motor deficits. Rather, temporal processing in all three systems seems to be impaired. Dyslexics may be unable to process fast incoming sensory information adequately in any domain.

Attention↗

Prognostic relevance of genetic alterations in the p32 region of chromosome 1 in neuroblastoma.

Thirty-six neuroblastomas were analysed for chromosome 1p alterations and their prognostic relevance. In 72% (26/36) of the patients, 1p alterations were identified in the tumours using 24 polymorphic loci ranging 1p22-1p36.3. LOH was identified in 25 children, and in 10 additional allelic imbalance was identified. In 1 child allelic imbalance was the sole alteration. Imbalance was termed as gain in intensity of one allele with or without reduction of the second allele (< 50%). The imbalance was identified in adjacent regions to the LOH. Two distinct regions of LOH were identified: 1p36.1-p36.3 and 1p31-p32. The common imbalance regions overlapped the common LOH regions. The children with LOH and imbalance had improved survival (100%) compared to the children with LOH only (26%) after 48 months of follow-up. The imbalance had an advantageous effect that is reflected by the improved outcome in children with other unfavourable clinical features.

Alleles↗

Additional chromosome 1q aberrations and der(16)t(1;16), correlation to the phenotypic expression and clinical behavior of the Ewing family of tumors.

The cytogenetic hallmark of the Ewing family of tumors is t(11,22)(q24;q12) in its simple, complex or variant forms and/or its molecular equivalent EWS/FLI, EWS/ERG rearrangement. Additional secondary consistent chromosomal aberrations include the der(16)t(1;16) and frequently, other chromosome 1q abnormalities leading to 1q overdosage. We studied whether these secondary cytogenetic changes are correlated to clinical features and phenotypic expression which may have a prognostic impact. Successful cytogenetic evaluation was performed in eight patients with a Ewing family tumor. In four of these, in addition to the primary aberration, chromosome 1q overdosage (including two with der (16)t(1;16)) was noted. Out of these four patients, two had metastatic disease at the time of evaluation, while in the other four, disease was localized. Morphologically, the tumors with the additional 1q aberration, revealed the pPNET subtype more frequently than the typical Ewing. They also expressed a higher degree of neural differentiation by neural marker immunocytochemistry, in comparison to tumors without the 1q aberration. Determination of the prognostic significance of this finding requires a longer follow-up with a larger group of patients.

Adolescent↗

A medical school's plan for anti-tobacco-use education in community schools and hospitals.

BACKGROUND: Tobacco use in the United States remains a significant health concern. In 1992, students at Dartmouth Medical School began a community service program that targeted the prevention of local tobacco use. METHODS: The program combined primary prevention, through education of school-aged children, with secondary prevention, through smoking cessation clinics. RESULTS: The program has received widespread community as well as national support for its actions. The program is in its initial stages of gathering data to determine whether there has been a significant impact on the tobacco use of the community. CONCLUSIONS: This paper is an introduction to the program's efforts, and a potential template for other medical schools to follow.

Adolescent↗

The effect of stair-step leaf transmission on the 'tongue-and-groove problem' in dynamic radiotherapy with a multileaf collimator.

When intensity-modulated fields are created using a multileaf collimator with dynamic leaf movement the potential problem for underdosage beneath the tongue-and-groove interleaf regions has been identified and a solution based on leaf-movement synchronization has been provided by Van Santvoort and Heijmen. Their first-order analysis ignored the transmission through an exposed stair-step. In this brief Note we provide the extended analysis including this contribution and show the effect on irradiation with synchronization. The result is that the synchronization approach of Van Santvoort and Heijmen solves the tongue-and-groove problem even when the transmission through the stair-step is considered, but partial synchronization is generally sufficient.

Health Physics↗

Effects of the stable prostacyclin analogue iloprost on mesenteric blood flow in porcine endotoxic shock.

OBJECTIVE: To determine the effects of the stable prostacyclin analog, iloprost, in a porcine model of endotoxin-induced mesenteric ischemia. DESIGN: Prospective, experimental, randomized, controlled study. SETTING: Animal research laboratory at a university medical center. INTERVENTIONS: Pigs were randomized to receive a constant infusion of iloprost (0.18 microg/kg/min) or an equivalent amount of carrier solution (normal saline) 30 mins before being infused with endotoxin (100 microg/kg over 1 hr). The infusion with iloprost or carrier solution was continued for the duration of the experiment. MEASUREMENTS AND MAIN RESULTS: Twelve pigs (six per group), weighing between 20 and 22 kg, underwent laparotomy during which a magnetic flowprobe was placed around the superior mesenteric artery and an ileal tonometer was inserted. Thirty minutes before they were infused with endotoxin, the animals were randomized to receive intravenous iloprost or normal saline. Endotoxin was infused centrally over a 60-min period. Animals received normal saline at a rate of 1.2 mL/kg/min which was begun at the start of the endotoxin infusion. Data were measured at the end of the endotoxin infusion (E60) and 1 hr later (E120). Mean arterial pressure was not affected by the dosage of iloprost used in this experiment. After resuscitation, the cardiac output returned to baseline in the iloprost-treated group but remained decreased in the control group (2.6 +/- 0.5 vs. 1.6 +/- 0.4 L/min). Superior mesenteric blood flow increased 34% above baseline levels in animals pretreated with iloprost (from 363 +/- 85 to 485 +/- 81 mL/min). The superior mesenteric PCO2 was significantly higher (53 +/- 9 vs. 40 +/- 5 torr; 7.1 +/- 1.2 vs. 5.3 +/- 0.7 kPa) and the ileal intramucosal pH was significantly lower (7.07 +/- .28 vs. 7.44 +/- .23) in the control group than in the iloprost-treated group. CONCLUSIONS: Pretreatment with intravenous iloprost effectively increased intestinal blood flow in this model of endotoxin-induced mesenteric ischemia. This action of the drug resulted in an attenuation of ileal intracellular acidosis. Since low-dose iloprost had no effect on mean arterial pressure, it may be a useful adjunct in the treatment of sepsis and septic shock.

Acidosis↗

Number and orientations of beams in intensity-modulated radiation treatments.

The fundamental question of how many equispaced coplanar intensity-modulated photon beams are required to obtain an optimum treatment plan is investigated in a dose escalation study for a typical prostate tumor. Furthermore, optimization of beam orientations to improve dose distributions is explored. A dose-based objective function and a fast gradient technique are employed for optimizing the intensity profiles (inverse planning). An exhaustive search and fast simulated annealing techniques (FSA) are used to optimize beam orientations. However, to keep computation times reasonable, the intensity profiles for each beam arrangement are still optimized using inverse planning. A pencil beam convolution algorithm is employed for dose calculation. All calculations are performed in three-dimensional (3D) geometry for 15 MV photons. DVHs, dose displays, TCP, NTCP, and biological score functions are used for evaluation of treatment plans. It is shown that for the prostate case presented here, the minimum required number of equiangular beams depends on the prescription dose level and ranges from three beams for 70 Gy plans to seven to nine beams for 81 Gy plans. For the highest dose level (81 Gy), beam orientations are optimized and compared to equiangular spaced arrangements. It is shown that (1) optimizing beam orientations is most valuable for a small numbers of beams (< or = 5) and the gain diminishes rapidly for higher numbers of beams; (2) if sensitive structures (for example rectum) are partially enclosed by the target volume, beams coming from their direction tend to be preferable, since they allow greater control over dose distributions; (3) while FSA and an exhaustive search lead to the same results, computation times using FSA are reduced by two orders of magnitude to clinically acceptable values. Moreover, characteristics of and demands on biology-based and dose-based objective functions for optimization of intensity-modulated treatments are discussed.

Algorithms↗

Dual role for AlF4(-)-sensitive G proteins in the function of T84 epithelial cells: transport and barrier effects.

T84 monolayers were studied to determine the effect of AlF4, an activator of heterotrimeric G proteins, on Cl-secretion and intestinal barrier function. Basolateral (but not apical) addition of AlF4- increased short-circuit current (I(sc)) and decreased transepithelial resistance. Preincubation with the heavy metal chelator deferoxamine showed that both effects were dependent on Al3+. The effect on I(sc) was abolished by the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid or in Cl(-)-free solutions, whereas the decrease in resistance was unaffected. AlF4- also increased intracellular Ca2+, as assessed via fura 2 fluorometry. AlF4- had no effect on adenosine 3',5'-cyclic monophosphate (cAMP) or guanosine 3',5'-cyclic monophosphate (cGMP) levels in T84 cells. The effect of AlF4- on transepithelial resistance was accompanied by a decrease in cellular F-actin as well as increased transepithelial fluxes of the paracellular markers mannitol and inulin. The results indicate that AlF4(-)-sensitive G proteins regulate both epithelial secretory and barrier functions, but via different pathways. AlF4- increases Cl- secretion via a Ca2+-dependent and cAMP- and cGMP-independent mechanism in T84 cells, whereas the decrease in resistance is independent of Ca2+.

Actins↗

Intestinal absorption of sodium dodecyl sulfate in the rodent: evidence for paracellular absorption.

Experiments were performed to define the mechanism of intestinal absorption of dodecyl sulfate (DS), an amphipathic organic anion whose chemical structure resembles that of dodecanoate, a C12 fatty acid anion. With jejunal segments perfused in single-pass fashion in the anesthetized rat, steady-state absorption of DS was concentration dependent, with the apparent permeability constant (P(app)) ranging from 4 to 22 x 10(-5) cm/s. When DS concentration was held constant and net water absorption was induced by decreasing perfusate osmolality, DS absorption increased in direct proportion to water absorption, suggesting absorption by solvent drag via the paracellular route. However, DS absorption continued even when water secretion was induced by a hypertonic perfusate. Consequently, for all experiments, DS absorption could be empirically described as the sum of two terms: 1) absorption in the absence of water absorption (P(app) = 5.6 x 10(-5) cm/s) and 2) absorption induced by water movement [(delta P(app)/delta water absorption) = 0.2 x 10(-5) cm x s(-1) x microl segment(-1) x min(-1)]. In a polarized epithelial monolayer of renal epithelial cells (Madin-Darby canine kidney cells), DS was absorbed predominantly by a paracellular pathway, as the absorption rate increased threefold when paracellular junction pore size was increased by the addition of cytochalasin D. The calculated apparent radius was 2.9 A, indicating that the cross section of the molecule, not its length, determined the rate of absorption. It is concluded that absorption of DS in the intact animal occurs slowly and mostly via the paracellular route, because the fixed negative charge on the molecule retards rapid passive entry into the enterocyte, as occurs with protonated fatty acids. That absorption of DS persisted despite net water secretion suggests a low level of transcellular absorption across the jejunal enterocyte also occurs.

Animals↗

Ketamine-midazolam versus meperidine-midazolam for painful procedures in pediatric oncology patients.

PURPOSE: To compare the efficacy, characteristics of onset/recovery, and safety of ketamine/atropine/midazolam with meperidine/midazolam used as premedication for painful procedures in children with cancer. METHODS: A randomized, double-blind crossover trial for two successive painful procedures (bone marrow aspiration or biopsy, lumbar puncture, or combined procedures) was performed at a referral-based pediatric hematology-oncology clinic and associated inpatient service of a university teaching hospital. Twenty-two children, aged 24 to 178 months, were enrolled and 18 (81.8%) completed the double-blind, crossover trial. Each child received intravenous premedication with either meperidine 2 mg/kg and midazolam 0.1 mg/kg (MM) or atropine 0.01 mg/kg, midazolam 0.05 mg/kg, and ketamine 1.5 mg/kg (KM) on one occasion followed by the alternative regimen on a second occasion. The initial premedication regimen was chosen by random assignment. RESULTS: Efficacy was assessed by a trained observer using the Observational Scale of Behavioral Distress-Revised (OSBD-R). Operator, nurse, parent, and patient opinions of efficacy were recorded on a visual analog scale (VAS). Side effects were monitored by pulse oximetry, nasal end-tidal capnography, and serial blood pressure measurements. Use of KM resulted in significantly less procedural distress than MM (1.37 +/- 2.20 v 7.04 +/- 8.06 OSBD-R units; P < .05). Both operators and nurses rated KM more effective than MM. KM use was associated with earlier readiness for the procedure (19.2 v 24.0 minutes) and more rapid recovery (39.3 v 74.6 minutes for removal of monitoring devices and 58.5 v 87.1 minutes for discharge). Procedures undertaken after ketamine sedation were associated with fewer side effects than observed with MM sedation (hypoxia, 17.7% v 82.4%; hypotension, 16.6% v 55.6%; reduced respiratory rate, 0% v 38.9%). The incidence of emergence reactions or behavioral abnormalities within 24 hours postprocedure was similar in both treatment groups. At 7 days postprocedure, no child had persistent behavioral abnormalities and all children had amnesia for the procedure. Parents and children expressed a preference for KM over MM in 12 of 18 cases (P < .05). CONCLUSION: A premedication regimen of KM produced superior sedation with a faster onset and recovery and fewer side effects than a MM combination.

Anesthetics↗

[Intestinal intercellular tight junctions. I. Structure and molecular mechanisms of regulation].

The existence of tight junctions between epithelial cells has been known for over 100 years, but their exact functions remained elusive until recently. The present paper summarizes the newest knowledge about morphology, molecular components and regulation of tight junctions. In the chapter about morphology the criteria for classification of epithelia as well as the importance of the "freeze fracture" electron-microscopic technique in forming our present ideas about the fine structure of tight junctions will be discussed. The two existing theories about the molecular composition of the resistance-forming barrier ("lipid-model" and "protein-model", resp.) and the important properties of the tight-junction-associated proteins characterized in the past years are discussed in the chapter about molecular components. Finally, in the last part of the paper the factors playing an important role in the regulation of tight junctions, including the cytoskeleton, the protein kinases A and C, the phospholipase C and two categories of the GTP-binding proteins are reviewed.

Animals↗

[Personal experiences with emergency coronary artery revascularization after failed PTCA--early and late results].

In recent years the equipment and techniques for percutaneous transluminal coronary angioplasty (PTCA) have been improved and today complex and distal stenoses are also treated in this way. Subsequent to failed PTCA some patients undergo emergency CABG. Between January 1991 and March 1995 3,520 patients have been treated by PTCA in our hospital. 61 patients (1.7%), mean age 61.1 years, underwent subsequent emergency CABG after PTCA. 46% had single-, 33% double and 21% had triple-vessel-disease, the mean left ventricular function (LVEF) was 65%. The mean number of bypass grafts was 1.9. The internal mammary arteries were never used under these emergency conditions. 9 patients (15%) developed perioperative myocardial infarction and in two of them the LVEF decreased under 30%. The hospital mortality was 6.6% (= 4 perioperative deaths). 6 of 61 patients were lost for follow-up; 90% of the hospitals survivors were followed for 244 months (mean 17). During this period there were 4 late deaths (3 cardiac and 1 non-cardiac). Actuarial survival at one year was 90%. 80% of the long-term survivors were in the NYHA functional classes I and II. In patients with double- or triple-vessel-disease PTCA almost always effects an incomplete revascularisation. Emergency CABG following failed PTCA is associated with an increased mortality and morbidity. The long-term prognosis is similar to that of an age-sex matched general population.

Adult↗