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Biomedical subjects

M Weinstein

Publications and source records attributed to M Weinstein.

At least 19 recordsLinked to original sources

Plica neuropathica: novel presentation of a rare disease.

Plica neuropathica is a rare condition involving complete matting of scalp hair. It typically occurs in otherwise healthy individuals, and in previous cases has been caused by either shampooing or neglect of hair. Cutting off the matted hair is the only solution. We present the case of a 14-year-old girl with a history of chronic illness and an acute infection presenting with plica neuropathica followed by complete hair loss. This unique case illustrates for the first time plica neuropathica in the absence of shampooing, and demonstrates that it can be associated with underlying illnesses and subsequent hair loss.

Adolescent↗

On neutron-gamma mixed field dosimetry with LiF:Mg,Ti at radiation protection dose levels.

The possibility of using the specific responses of the high temperature Peaks 6 and 7 and Peaks 4 and 5 to different LET radiations was mentioned in the past mainly for very high doses. The applicability of the two regions method for thermal neutrons--gamma ray mixed field dosimetry was investigated by analysing the response of LiF:Mg,Ti dosemeters irradiated to different ratios of thermal neutrons and gamma rays at radiation protection dose levels encountered in routine work conditions, up to approximately 50 mSv. The Region of Interest method was used to define the areas of the Peaks 4 + 5 and 6 + 7. We found that a simple algorithm can be used to determine with good accuracy the separate contributions of neutron and gamma doses.

Computer Simulation↗

Determination of quality parameters from statistical analysis of routine TLD dosimetry data.

Following the as low as reasonably achievable (ALARA) practice, there is a need to measure very low doses, of the same order of magnitude as the natural background, and the limits of detection of the dosimetry systems. The different contributions of the background signals to the total zero dose reading of thermoluminescence dosemeter (TLD) cards were analysed by using the common basic definitions of statistical indicators: the critical level (L(C)), the detection limit (L(D)) and the determination limit (L(Q)). These key statistical parameters for the system operated at NRC-Negev were quantified, based on the history of readings of the calibration cards in use. The electronic noise seems to play a minor role, but the reading of the Teflon coating (without the presence of a TLD crystal) gave a significant contribution.

Artifacts↗

Structured terminology for capsule endoscopy: results of retrospective testing and validation in 766 small-bowel investigations.

BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) is an effective means of investigating the small bowel in patients with gastrointestinal diseases. Computerized reports are frequently used in endoscopy, and the Minimal Standard Terminology (MST) has been promoted by endoscopy societies as the official vocabulary for endoscopy. The aims of this study were to design a lexicon for CE reports based on the principles of the MST and to validate lists of terms for describing findings and reasons for performing a CE by cross-matching them with the results of CE procedures collected during ongoing clinical studies. MATERIALS AND METHODS: A consensus-based Capsule Endoscopy Structured Terminology (CEST) was developed by experts involved in CE studies. Lists of terms suitable for CE were designed for the various sections of an endoscopic report. They were then correlated with the corresponding MST lists for duodenal and intestinal endoscopy. The results of 766 CE procedures, collected in an electronic case record form (eCRF), were analyzed to provide lists of reasons for performing the procedures and of the findings. The eCRF provided only a limited number of items for each data field, along with free-text facilities. Only descriptions pertaining to the small bowel were analyzed. Lists of terms were then reviewed by two experts to group obvious synonyms. The accuracy of the CEST was defined beforehand as the capability to describe 90 % of entries. RESULTS: A total of 766 CE procedures were analyzed. The eCRF included 824 entries as reasons for the examination in 655 CEs (1.3 per procedure). These represented 122 different expressions. After grouping of synonyms, 28 expressions remained. Among them, 10 were matched with terms from the list of reasons for performing CE offered in the CEST. These were the most frequently used, accounting for 768 entries in this field (93.2 %). All eCRFs contained at least one description of findings. A total of 109 CE procedures were classified as normal (14.3 %). A total of 2624 entries for abnormal findings were recorded for 657 procedures (4.0 per procedure). In all, 213 different expressions were used to describe abnormal findings. After grouping of synonyms, 52 expressions remained. Among these, 27 were matched with terms from the list of findings in the CEST, covering 2403 entries (91.6 %). CONCLUSIONS: In this study, CEST terms were capable of describing more than 90 % of the reasons for performance and of the findings in an unselected set of CE procedures. CEST is therefore suitable for use as the standard lexicon for CE reports. Adopted as a standard, it could significantly improve the quality of the data collected and reported in CE studies.

Endoscopy, Gastrointestinal↗

Small-bowel intussusception around a gastrojejunostomy tube resulting in ischemic necrosis of the intestine.

Gastrojejunostomy (GJ) tube feeding has made a significant difference in the lives of children with oropharyngeal motor problems and severe gastroesophageal reflux disease. It may, however, also lead to small-bowel intussusception. Previously, these intussusceptions have been reported as intermittent, self limiting, and innocuous. We report a case of a GJ-tube-related small-bowel intussusception that resulted in ischemic necrosis of the bowel. This case suggests that close monitoring and confirmation of successful reduction is necessary in the treatment of GJ-tube-related small-bowel intussusception.

Enteral Nutrition↗

On fading corrections for LiF:Mg,Ti irradiated by thermal neutrons.

The phenomena of preirradiation and postirradiation fading of LiF:Mg,Ti phosphors are considered a significant practical problem in routine dosimetry because of the uncertainties introduced, especially for mixed neutron-gamma dosimetry, as different fading corrections may be necessary for the gamma and neutron contributions. We have investigated if the region of interest (ROI) method is applicable to minimizing the fading effect for thermal neutron irradiation as it is for gamma irradiation. By employing the ROI method, which consists of integration between channel 31 below the glow curve maximum and channel 16 above the glow curve maximum, a constant dose value was obtained for the period of 90 d. Thus, by employing the ROI method, a fading independent evaluation of the thermal neutron dose can be made.

Algorithms↗

The roles of Smad2 and Smad3 in the development of chemically induced skin tumors in mice.

Transforming growth factor-beta (TGF-beta) plays a complex role in skin carcinogenesis, acting as a suppressor early in tumor development but later as a promoter. Smad proteins are important intracellular mediators of TGF-beta signaling. To determine the effect of disrupting Smad genes and TGF-beta signaling on chemically induced skin carcinogenesis in mice, transgenic mice heterozygous for Smad2 or Smad3 deletions and wild-type controls were treated with topical dimethylbenzanthracene for 7 months. Tumor multiplicity, type, and degree of differentiation were assessed by histopathology and immunohistochemistry. Smad3(+/-) mice developed significantly fewer tumors than the wild-type group (P < 0.05). This indicated a possible oncogenic function for Smad3 in skin carcinogenesis. Smad2(+/-) mice formed less-differentiated tumors than their wild-type counterparts, supporting a tumor suppressor role for Smad2. There was a significant difference (P < 0.05) in tumor type between Smad2(+/-) and Smad3(+/-) groups, suggesting that Smad2 and Smad3 may regulate different targets.

9,10-Dimethyl-1,2-benzanthracene↗

Timing of menopause and patterns of menstrual bleeding.

Age at menopause is associated with a variety of health outcomes. Menstrual histories, both as markers of physiologic function and through their potential association with age at menopause, have also been investigated for their links to health outcomes. This study used data from a cohort of women from the United States who provided prospectively recorded data on their menstrual cycles for many years. Dr. Alan Treloar (University of Minnesota) originally recruited the women in the 1930s; the authors used data reported by these women from 1930 through 1977. They identified nuanced characteristics of menstrual histories that were strongly predictive of the onset of menopause, focusing on measures of central tendency (the mean), variability (standard deviation), and serial irregularity (approximate entropy), the last of which quantifies a continuum that ranges from totally ordered to completely random. They controlled for other characteristics known to affect age at menopause, including use of exogenous hormones, number of births, and extent of breastfeeding. Although cycle length and variability increased with the approach of menopause, the authors found that serial irregularity decreased and was a strong predictor of its onset. This finding constitutes an important piece of information not attainable with conventional statistical summaries of menstrual histories.

Adolescent↗

On the determination of the post-irradiation time from the glow curve of TLD-100.

The ratio of peak 3 to the sum of peaks 4 + 5 in TLD-100 was measured for various pre-irradiation and post-irradiation time periods, under conditions characteristic of routine personal dosimetry. It was confirmed that the value of this ratio depends only on the elapsed time between the prior readout and the present one, independent of the moment when the irradiation took place during the total time interval (storage time). This effect indicates that fading of peak 3 seems to be due mainly to changes in the unoccupied traps, and not to decay of trapped charges, being almost independent of the presence of electrons or holes in the traps. This observation leads to the conclusion that the suggestions in the past to use the decay of peak 3 in TLD-100 for the measurement of the elapsed time between irradiation and readout may have been wrong. On the other hand, the decay of peak 2 can be used to measure the elapsed time from irradiation, since the rate of decay is different when related to pre-irradiation and post-irradiation times, indicating a much higher decay rate of the trapped charges (Randall-Wilkins decay). However, because of the fast decay rate of peak 2, its use for determination of the elapsed time since irradiation is of little practical significance.

Equipment Failure Analysis↗

Non-radiation induced signals in TL dosimetry.

One source of background signals, which are non-radiation related, is the reader system and it includes dark current, external contaminants and electronic spikes. These factors can induce signals equivalent to several hundredths of mSv. Mostly, the effects are minimised by proper design of the TLD reader, but some effects are dependent on proper operation of the system. The other main group of background signals originates in the TL crystal and is due to tribothermoluminescence, dirt, chemical reactions and stimulation by visible or UV light. These factors can have a significant contribution, equivalent to over several mSv, depending on whether the crystal is bare or protected by PTFE. Working in clean environments, monitoring continuously the glow curves and performing glow curve deconvolution are suggested to minimise non-radiation induced spurious signals.

Crystallization↗

Calibration of the Ph. Eur. BRP Batch 3/Mega 2 (US/FDA) standard for human coagulation factor VIII concentrate for use in the potency assay.

The European Pharmacopoeia Biological Reference Preparation Batch 3/Mega 2 (United States/Food and Drug Administration) (Ph. Eur. BRP Batch 3/Mega 2 (US/FDA)) was developed as an internationally available, common working standard to replace the dwindling stocks of Mega 1 (the current US standard) and Ph. Eur. BRP Batch 2 (the current European standard). The potency was assigned in an international collaborative study with reference to four currently established standards, Ph. Eur. BRP batch 2, WHO 5th and 6th International Standard and Mega 1. Thirty-eight laboratories participated in the collaborative study. Each laboratory was asked to perform four independent assays. Participants used either the one stage clotting assay or the chromogenic assay or both. This publication reports the results obtained with both assays. The summary and conclusion, however highlight the results mainly with respect to the chromogenic assay, which is the assay prescribed in the European Pharmacopoeia. Data were analysed for both assays separately. A consensus potency value was calculated as the unweighted average of mean potencies determined against the four standards. A potency of 8.6 IU/vial as determined in the chromogenic substrate method was assigned to the candidate standard. Inter-laboratory agreement as assessed by calculation of the geometric coefficient of variation was below 10% for mean potencies against all four calibrators for the chromogenic assay. Ph. Eur. BRP Batch 3/Mega 2 (US/FDA) is a freeze-dried, plasma derived, high-purity concentrate. The material was filled into approximately 100,000 vials and lyophilised to a final residual moisture of < or = 2%. Approximately 90,000 vials of the standard are available, equally shared between the two co-ordinating centers. Based on the stability studies, the predicted mean percentage loss per year at -20 degrees C is 0.000% and thus the candidate standard appears to be stable. The Ph. Eur. BRP batch 3 was adopted by the European Pharmacopoeia Commission in November 2001.

Blood Coagulation Tests↗

Fibroblast growth factors in regenerating limbs of Ambystoma: cloning and semi-quantitative RT-PCR expression studies.

Urodele amphibians (newts and salamanders) have the ability to regenerate amputated limbs throughout their life span. Because fibroblast growth factors (Fgfs) play important roles in developing limbs, we initiated studies to investigate these growth factors in regenerating limbs. Partial cDNAs of Fgf4, 8, and 10 were cloned from both the Mexican axolotl, Ambystoma mexicanum, and locally collected spotted salamander, Ambystoma maculatum, two salamanders well recognized for their regenerative capabilities. cDNAs from the two Ambystoma species were virtually identical, ranging from 97-100% nucleotide identity. Axolotl Fgf4, 8, and 10 showed nucleotide sequence identity with chick Fgf4, 8, and 10 of 79%, 83%, and 72%, respectively. RT-PCR showed that these growth factors are expressed in regenerating axolotl limbs as well as in developing salamander larvae at the three-digit forelimb stage. Fgf8 and 10 are upregulated during regeneration and thus may be involved in distal signaling similar to that of the developing chick limb. Fgf4, however, was undetectable by RT-PCR in the distal tips of regenerates, suggesting that it does not play the same role in limb regeneration that it does in limb development. We also investigated the role these Fgfs may have in the nerve-dependence of regeneration. They were expressed similarly in aneurogenic and innervated limbs, suggesting that they are not the neurotrophic factors responsible for nerve-dependence. Denervation prevented Fgf8 and 10 upregulation, suggesting Fgf pathways are downstream of nerve-dependence. These data highlight important similarities and differences in Fgf expression between limb development and limb regeneration. J. Exp. Zool. 290:529-540, 2001.

Ambystoma↗

Respiratory symptoms at age 8 years in a cohort of very low birth weight children.

The childhood respiratory consequences of very low birth weight (birth weight < or =1,500 g) are incompletely understood, especially since the introduction of recent changes in neonatal care. To assess prevalence, trends, and risk factors for respiratory symptoms, the authors followed to age 8 years a cohort of 384 very low birth weight children from six regional neonatal intensive care units in Wisconsin and Iowa who were born between August 1, 1988, and June 30, 1991. A control group of 154 Wisconsin schoolchildren was also assembled. Respiratory symptoms in the past 12 months and history of asthma ("asthma ever") were reported by parents on a questionnaire used in the International Study of Asthma and Allergies in Childhood (ISAAC). Control group prevalence resembled ISAAC prevalence worldwide and in Canada, but respiratory symptoms were twice as common among very low birth weight children. With advent of the availability of pulmonary surfactants, the prevalence of wheezing at age 8 decreased from 50% to 16% (p = 0.002) among children with bronchopulmonary dysplasia, but it increased from 14% to 38% among those with milder neonatal respiratory disease. Bronchopulmonary dysplasia, family history of asthma, smoking in the household, and patent ductus arteriosus were predictive of wheezing in the previous 12 months. Antenatal steroid therapy had a borderline-significant protective association with wheezing (odds ratio = 0.56, 95% confidence interval: 0.29, 1.1). There were interaction effects between several of the predictors.

Asthma↗

Antagonistic effects of Smad2 versus Smad7 are sensitive to their expression level during tooth development.

Members of the transforming growth factor-beta (TGF-beta) superfamily regulate cell proliferation, differentiation, and apoptosis, controlling the development and maintenance of most tissues. TGF-beta signal is transmitted through the phosphorylation of Smad proteins by TGF-beta receptor serine/threonine kinase. During early tooth development, TGF-beta inhibits proliferation of enamel organ epithelial cells but the underlying molecular mechanisms are largely unknown. Here we tested the hypothesis that antagonistic effects between Smad2 and Smad7 regulate TGF-beta signaling during tooth development. Attenuation of Smad2 gene expression resulted in significant advancement of embryonic tooth development with increased proliferation of enamel organ epithelial cells, while attenuation of Smad7 resulted in significant inhibition of embryonic tooth development with increased apoptotic activity within enamel organ epithelium. These findings suggest that different Smads may have differential activities in regulating TGF-beta-mediated cell proliferation and death. Furthermore, functional haploinsufficiency of Smad2, but not Smad3, altered TGF-beta-mediated tooth development. The results indicate that Smads are critical factors in orchestrating TGF-beta-mediated gene regulation during embryonic tooth development. The effectiveness of TGF-beta signaling is highly sensitive to the level of Smad gene expression.

Animals↗

Functional characterization of transforming growth factor beta signaling in Smad2- and Smad3-deficient fibroblasts.

A prominent pathway of transforming growth factor (TGF)-beta signaling involves receptor-dependent phosphorylation of Smad2 and Smad3, which then translocate to the nucleus to activate transcription of target genes. To investigate the relative importance of these two Smad proteins in TGF-beta1 signal transduction, we have utilized a loss of function approach, based on analysis of the effects of TGF-beta1 on fibroblasts derived from mouse embryos deficient in Smad2 (S2KO) or Smad3 (S3KO). TGF-beta1 caused 50% inhibition of cellular proliferation in wild-type fibroblasts as assessed by [(3)H]thymidine incorporation, whereas the growth of S2KO or S3KO cells was only weakly inhibited by TGF-beta1. Lack of Smad2 or Smad3 expression did not affect TGF-beta1-induced fibronectin synthesis but resulted in markedly suppressed induction of plasminogen activator inhibitor-1 by TGF-beta1. Moreover, TGF-beta1-mediated induction of matrix metalloproteinase-2 was selectively dependent on Smad2, whereas induction of c-fos, Smad7, and TGF-beta1 autoinduction relied on expression of Smad3. Investigation of transcriptional activation of TGF-beta-sensitive reporter genes in the different fibroblasts showed that activation of the (Smad binding element)(4)-Lux reporter by TGF-beta1 was dependent on expression of Smad3, but not Smad2, whereas activation of the activin response element-Lux reporter was strongly suppressed in S2KO fibroblasts but, on the contrary, enhanced in S3KO cells. Our findings indicate specific roles for Smad2 and Smad3 in TGF-beta1 signaling.

Animals↗