Anti-Emm in a pregnant patient--case report.

A 23-year-old primigravida of North African origin presented with a positive antibody screen at booking at 15 weeks of gestation. An antibody to a high-frequency antigen (HFA) of unknown identity was detected, which was reactive with the red blood cells of the father. This led to several challenges including antibody identification, clinical monitoring to detect signs of haemolytic disease of the foetus and newborn (HDFN) and compatible blood in case perinatal transfusion was needed. Anti-Emm was identified 2 months post-partum. This is the first published case which describes a pregnant patient with anti-Emm.

Oral sex is associated with reduced incidence of recurrent miscarriage.

A possible way of immunomodulation of the maternal immune system before pregnancy would be exposure to paternal antigens via seminal fluid to oral mucosa. We hypothesized that women with recurrent miscarriage have had less oral sex compared to women with uneventful pregnancy. In a matched case control study, 97 women with at least three unexplained consecutive miscarriages prior to the 20th week of gestation with the same partner were included. Cases were younger than 36 years at time of the third miscarriage. The control group included 137 matched women with an uneventful pregnancy. The association between oral sex and recurrent miscarriage was assessed with conditional logistic regression, odds ratios (ORs) were estimated. Missing data were imputed using Imputation by Chained Equations. In the matched analysis, 41 out of 72 women with recurrent miscarriage had have oral sex, whereas 70 out of 96 matched controls answered positive to this question (56.9% vs. 72.9%, OR 0.50 95%CI 0.25-0.97, p = 0.04). After imputation of missing exposure data (51.7%), the association became weaker (OR 0.67, 95%CI 0.36-1.24, p = 0.21). In conclusion, this study suggests a possible protective role of oral sex in the occurrence of recurrent miscarriage in a proportion of the cases. Future studies in women with recurrent miscarriage explained by immune abnormalities should reveal whether oral exposure to seminal plasma indeed modifies the maternal immune system, resulting in more live births.

Assessment of novel cardiovascular biomarkers in women with a history of recurrent miscarriage.

OBJECTIVES: A history of recurrent miscarriage is associated with future cardiovascular disease. The aim of this study was to determine novel cardiovascular biomarkers in women with a history of recurrent miscarriage as this might lead to a better understanding of the association. STUDY DESIGN: Women who visited the recurrent miscarriage clinic at Leiden University Medical Centre (between 2000 and 2010), and had three consecutive miscarriages ≤30 years were invited to participate in this follow-up study (between 2012 and 2014). The reference group consisted of women with at least one uncomplicated pregnancy and a history of no miscarriage, matched on zip code, age, and date of pregnancy. MAIN OUTCOME MEASURES: Cardiovascular biomarkers were determined, classified into; inflammation (HsCRP, lipoprotein-associated phospholipase A2), thrombosis (homocysteine, folate, anti-cardiolipin antibodies and anti-ß-2-glycoprotein antibodies), lipid metabolism (lipoprotein(a)), renal function (creatinine, microalbuminuria), myocardial damage (N-terminal pro-brain natriuretic peptide, high sensitive TroponineT) and multiple mechanisms (albumin, vitamin D). RESULTS: In both groups, 36 women were included. Women with recurrent miscarriage had a significantly higher median HsCRP (1.49 mg/L) compared to women with no miscarriage (1.01 mg/L, p = 0.03) and a significantly lower mean albumin (46.0 vs 47.6g/L, p = 0.004) and vitamin D (55.6 vs 75.4nmol/L, p = 0.007), respectively. Differences remained after adjustments for classic cardiovascular risk factors (BMI, smoking, diabetes mellitus, and hypertension). CONCLUSIONS: Our findings suggest a proinflammatory state in women with a history of recurrent miscarriage, which suggests a less optimal health, compared to women with no miscarriage. More research (observational and intervention) is warranted to investigate the association with vitamin D.

Pathogenesis of malignant histiocytic lymphoma induced by silica in a colony of specificpathogen-free Wistar rats.

The occurrence of malignant histiocytic lymphomas (MHLT) after an intrapleural inoculation of silica and the presence of a hyperplastic or granulomatous reaction to the silica were confirmed in cesarean-derived barrier-maintained inbred W rats. A specific hyperplastic reaction in the silica granulomas preceded the appearance of MHLT. Hyperplastic changes were observed when the absolute monocyte count at weeks 25-30 was slightly higher than that seen in the controls. Silica injected intrapleurally penetrated the thymus tissue but the carbon and coal dusts and the silica, which was administered by other routes, did not involve the thymus. Also, silica was the sole dust, when introduced into the coelomic cavities that produced MHLT, which grew rapidly on entering the thymus. Rats that died with MHLT had widespread dissemination with malignant foci situated most consistently above the diaphragm.

Changes with age in the hematopoietic system in a cesarean-derived, barrier-maintained colony of Wistar rats.

In a colony of cesarean-derived barrier-maintained inbred W rats given saline injections into the right pleural cavities, histologic and cytologic changes due to age were examined in the bone marrow, lymphatic tissue, and lungs; hematologic trends were also evaluated. The thymus showed two changes with age: 1) atrophy, which was evidenced by plasma cells near the blood vessels and among the cords of epithelial cells; and 2) disruption of the normal architecture of the gland. In all available thymuses, changes showed a transition toward malignancy. As the bone marrow showed increasing cellularity with time, polymorphonuclear cells and precursors appeared to increase. In lymph nodes, lymphocytes in the paracortical area were excessive and resembled the lymphocytes of the "lymphoid bursts" found in the thymus. In the lungs, small parabronchial and paravascular collections of mononuclear cells, occurring with slightly increasing frequency with age, were consistently found; however, any lung disease associated with these cells was not evident. In the blood, absolute numbers of mononuclear and polymorphonuclear cells were altered.

Antiandrogens do not reverse androgen-induced inhibition of sex hormone-binding globulin levels in adult female rhesus monkeys.

Studies were done to determine if changes in plasma sex hormone-binding globulin (SHBG) levels could serve as a specific marker of androgenic and antiandrogenic activities in rhesus monkeys. Treatment of adult female monkeys for 11 days with 17 alpha-methyltestosterone (MeT) produced dose and time-dependent reductions in SHBG levels. However, the non-steroidal antiandrogen flutamide (80 mg/monkey.day) did not inhibit the reduction in SHBG levels when coadministered with MeT, nor did it have an effect on SHBG levels when given alone. In contrast, the steroidal antiandrogens Win 49596 (100 mg/monkey.day) and cyproterone acetate (80 mg/monkey.day) significantly (P less than 0.01) reduced SHBG plasma concentration to about 50% of pretreatment control values whether given alone or in combination with MeT. Furthermore, Win 49596 reduced SHBG levels at doses as low as 4 mg/monkey, whereas cortico-steroid-binding globulin levels were not affected. In ovariectomized monkeys, MeT treatment (4 mg/monkey.day for 15 days) reduced plasma SHBG levels to 42% of pretreatment values and delayed the onset of withdrawal menstrual bleeding compared to that in controls. When administered concurrently with MeT, flutamide (100 mg/monkey.day) antagonized the effect on withdrawal bleeding, but was without effect on SHBG levels. Therefore, plasma SHBG levels cannot be used as a specific indicator of androgenic or antiandrogenic activity and may not be regulated through the classical androgen receptor.

A novel, nonsteroidal inhibitor of androgen binding to the rat androgen binding protein: diethyl [[[3-(2,6-dimethyl-4-pyridinyl)-4-fluorophenyl]amino]methylene] propanedioate.

In vitro binding studies demonstrate the binding specificity of a series of 4-aryl-2,6-dimethylpyridines for the rat epididymal androgen binding protein (rABP). The compounds bound competitively to rABP but have very weak or no demonstrable affinity for rat ventral prostate androgen receptor and human sex hormone binding globulin. In particular, compound 11, diethyl [[[3-(2,6-dimethyl-4-pyridinyl)-4-fluorphenyl]amino]methylene] propanedioate, bound with high affinity to rABP (binding affinity about 1/3 that of the endogenous ligand 5 alpha-dihydrotestosterone). However, additional in vitro binding studies indicated that 11 did not bind to testicular or epididymal ABP from rabbit, rhesus monkey, and human. Nevertheless, the specificity and relatively high affinity of these nonsteroidal compounds make them unique and potentially ideal agents for the study of the role of ABP in spermatogenesis and sperm maturation in the rat.

Accuracy of data in computer-based patient records.

Data in computer-based patient records (CPRs) have many uses beyond their primary role in patient care, including research and health-system management. Although the accuracy of CPR data directly affects these applications, there has been only sporadic interest in, and no previous review of, data accuracy in CPRs. This paper reviews the published studies of data accuracy in CPRs. These studies report highly variable levels of accuracy. This variability stems from differences in study design, in types of data studied, and in the CPRs themselves. These differences confound interpretation of this literature. We conclude that our knowledge of data accuracy in CPRs is not commensurate with its importance and further studies are needed. We propose methodological guidelines for studying accuracy that address shortcomings of the current literature. As CPR data are used increasingly for research, methods used in research databases to continuously monitor and improve accuracy should be applied to CPRs.

The accuracy of medication data in an outpatient electronic medical record.

OBJECTIVE: To measure the accuracy of medication records stored in the electronic medical record (EMR) of an outpatient geriatric center. The authors analyzed accuracy from the perspective of a clinician using the data and the perspective of a computer-based medical decision-support system (MDSS). DESIGN: Prospective cohort study. METHODS: The EMR at the geriatric center captures medication data both directly from clinicians and indirectly using encounter forms and data-entry clerks. During a scheduled office visit for medical care, the treating clinician determined whether the medication records for the patient were an accurate representation of the medications that the patient was actually taking. Using the available sources of information (the patient, the patient's vials, any caregivers, and the medical chart), the clinician determined whether the recorded data were correct, whether any data were missing, and the type and cause for each discrepancy found. RESULTS: At the geriatric center, 83% of medication records represented correctly the compound. dose, and schedule of a current medication; 91% represented correctly the compound. 0.37 current medications were missing per patient. The principal cause of errors was the patient (36.1% of errors), who misreported a medication at a previous visit or changed (stopped, started, or dose-adjusted) a medication between visits. The second most frequent cause of errors was failure to capture changes to medications made by outside clinicians, accounting for 25.9% of errors. Transcription errors were a relatively ucommon cause (8.2% of errors). When the accuracy of records from the center was analyzed from the perspective of a MDSS, 90% were correct for compound identity and 1.38 medications were missing or uncoded per patient. The cause of the additional errors of omission was a free-text "comments" field-which it is assumed would be unreadable by current MDSS applications-that was used by clinicians in 18% of records to record the identity of the medication. CONCLUSIONS: Medication records in an outpatient EMR may have significant levels of data error. Based on an analysis of correctable causes of error, the authors conclude that the most effective extension to the EMR studied would be to expand its scope to include all clinicians who can potentially change medications. Even with EMR extensions, however, ineradicable error due to patients and data entry will remain. Several implications of ineradicable error for MDSSs are discussed. The provision of a free-text "comments" field increased the accuracy of medication lists for clinician users at the expense of accuracy for a MDSS.

In vitro pharmacology of cryptophycin 52 (LY355703) in human tumor cell lines.

PURPOSE: Cryptophycin 52 (LY355703) is a new member of the cryptophycin family of antitumor agents that is currently undergoing clinical evaluation for cancer chemotherapy. The mechanism of action of the cryptophycin class of compounds is associated with an action on microtubules. This report details the pharmacological profile of this new clinical compound in a panel of human tumor cell lines. METHODS: Antiproliferative effects of cryptophycin 52 were measured indirectly by detection of the metabolic reduction of alamarBlue. Cytoxicity was assessed by enzymatic dye activation (calcein AM) combined with dye exclusion (ethidium homodimer) and by clonogenicity assay. Cell cycle effects were evaluated using flow cytometry and fluorescence microscopy. RESULTS: Both antiproliferative and cytotoxic effects of cryptophycin 52 were concentration- and time-dependent. IC50 values for antiproliferative activity in both solid and hematologic tumor cell lines were in the low picomolar range, and without exception, were significantly below values for the antimitotic agents paclitaxel and vinblastine. Flow cytometry and microscopic examination of tumor cells treated with cryptophycin 52 indicated that they accumulated in the mitotic phase of the cell cycle. Cryptophycin 52 was tested for its sensitivity to multidrug-resistance in several paired cell lines in which a sensitive parental line was matched with a multidrug-resistant derivative line. The resistant lines have been shown to over express Pgp and/or MRP multidrug-resistance transport factors. Compared to other antimitotic agents (paclitaxel, vinblastine, vincristine), the potency of cryptophycin 52 was shown to be minimally affected in multidrug-resistant cells compared to their sensitive parental lines. CONCLUSION: Cryptophycin 52 has potent antimitotic, antiproliferative and cytotoxic activity in in vitro human tumor cell models. It is significantly more potent and less sensitive to multidrug resistance mechanisms than other antimitotic antitumor agents currently used in cancer therapy. These characteristics may translate into therapeutic advantages for the clinical use of cryptophycin 52 in cancer chemotherapy.

Representing and developing temporally abstracted knowledge as a means towards facilitating time modeling in medical decision-support systems.

The utilization of the appropriate level of temporal abstraction is an important aspect of time modeling. We discuss some aspects of the relation of temporal abstraction to important knowledge engineering parameters such as model correctness, ease of model specification, knowledge availability, query completeness, inference tractability, and semantic clarity. We propose that versatile and efficient time-modeling formalisms should encompass ways to represent and reason at more than one level of abstraction, and we discuss such a hybrid formalism. Although many research efforts have concentrated on the automation of specific temporal abstractions, much research needs to be done in understanding and developing provably optimal abstractions. We provide an initial framework for studying this problem in a manner that is independent of the particular problem domain and knowledge representation, and suggest several research challenges that appear worth pursuing.

Pathophysiology related to peripheral vascular disease.

The problems of peripheral vascular diseases are varied and sometimes complex. The major and most common disease is arteriosclerosis obliterans. This problem will continue as the life expectancy increases. The severity of the disease compromises the quality of life. An understanding of the pathophysiologic process is necessary to enhance the quality of life and prevent the terrible and disfiguring complications which can arise as a result of insufficient knowledge.

The patient with abdominal injuries.

Pathology of blunt and penetrating abdominal trauma is presented in specific sections. Samples of a focused cue search, nursing diagnostic statements, and defining characteristics are included. Utilization of the aforementioned items are discussed within the context of a case involving victims of an accident resulting from a high-speed chase.

An automatic indexing method for medical documents.

This paper describes MetaIndex, an automatic indexing program that creates symbolic representations of documents for the purpose of document retrieval. MetaIndex uses a simple transition network parser to recognize a language that is derived from the set of main concepts in the Unified Medical Language System Metathesaurus (Meta-1). MetaIndex uses a hierarchy of medical concepts, also derived from Meta-1, to represent the content of documents. The goal of this approach is to improve document retrieval performance by better representation of documents. An evaluation method is described, and the performance of MetaIndex on the task of indexing the Slice of Life medical image collection is reported.

Immunology and asbestos.

A population exposed to asbestos while working in a dockyard has been studied longitudinally. Immunological tests using markers for subsets of lymphocytes and monocytes were employed. Evidence is presented that suggests that those with progressing pulmonary fibrosis may be pinpointed. From animal experimental work in relation to mesothelioma, it is suggested that macrophages may play a role in the control of this tumour.