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Biomedical subjects

R E Wenk

Publications and source records attributed to R E Wenk.

18 recordsLinked to original sources

How frequent is heteropaternal superfecundation?

A newly discovered case of heteropaternal superfecundation (HS) is reported. Three HS cases were found in a parentage test database of 39,000 records. The frequency of HS among dizygotic twins whose parents were involved in paternity suits is 2.4%. Although the study population appears similar to the general population with respect to twinning data, inferences about the frequency of HS in other populations should be drawn with caution.

Adolescent

Two-man and two-sibling paternity cases.

Traditional genetic marker systems rarely fail to resolve paternity disputes when two or more men are accused, except when men are brothers. A sibling of the biologic father may not be excluded by these laboratory tests and sometimes yields calculated odds of paternity that are equal to or higher than the true male parent. Resolved two-brother cases were compared with resolved cases involving two unrelated men. In each case, the residual odds of paternity were determined for each man and the greater was divided by the lesser to produce a paternity fraction. The paternity fraction is a useful indicator of biologic parentage when it exceeds a value of 10 (log10 of-the-odds score greater than or equal to 1). Tests for alleles at highly heterozygous loci are indicated in initial laboratory evaluations of cases involving brothers. Human leukocyte antigen and variable number of tandem repeat polymorphisms appear suitable.

Alleles

Technical progress in parentage analysis.

At the turn of the 20th century, Mendel's laws were found to be applicable to human blood groups. Within two decades, blood group genetics were applied to problems of parentage. Expansion of immunohematology into leukocyte antigen identification produced the single most informative, expressed polymorphism. About the same time, analysis of a great number of soluble protein polymorphisms followed advances in electric separation methods, enzymology, and immunochemistry. As new, independent loci were discovered, the power to exclude the falsely accused increased, and it became possible to apply Bayesian principles to determined probabilities of biologic relationships. The revolution in nucleic acid technology has dramatically improved analysis and statistical inferences. By the turn of the 21st century, laboratories should be able to determine biologic parentage with virtual certainty.

Blood Group Antigens

alpha-fetoprotein and screening markers of congenital disease.

Alpha-fetoprotein (AFP) is produced in the gut and liver during fetal life and appears to act like albumin in the adult. Because AFP appears in the maternal circulation during pregnancy, interest has been focused on its measurement in maternal serum to predict fetal abnormality. In addition, AFP, as an embryonic product, is elevated in certain malignant states. This article provides a summary of current clinical knowledge of AFP and its applications.

Amniotic Fluid

Parentage analysis by endonuclease shattering of hypervariable DNA.

Single-locus DNA probes for tandem repeat sequences are now used in conjunction with particular endonucleases to characterize heritable restriction fragment lengths in parentage tests. Southern blots of this type, however, demonstrate only two attributes of an allele: its length and the presence of nucleotide sequences that are complementary to the probe. Not all restriction fragments of the same apparent length that react with the same probe are identical. Differences between comigrating fragments can be detected by the selection of a restriction enzyme that recognizes sites in a subset of the repeat sequences, and the information content of these loci is therefore increased. This report describes a paternity case in which two brothers appeared, after DNA phenotyping using Hinf I, to be the father. A second phenotyping using Hae III excluded one of the brothers.

Alleles

Naturally occurring human antibodies against two distinct functional domains in the heavy chain of FXI/FXIa.

We have isolated and probed the mechanism of action of two naturally occurring antibodies (Baltimore and Winston-Salem) against factor XI (FXI), that developed in patients congenitally deficient in FXI after replacement therapy. Purification on immobilized protein A and neutralization with monospecific antibodies against IgG heavy and light chain subtypes indicated that both antibodies were of restricted heterogeneity. Both Winston-Salem (IgG3 kappa) and Baltimore (IgG1 kappa) completely inhibited FXI coagulant activity at titers of 200 and 8 Bethesda units, respectively. Immunoaffinity columns prepared from each antibody were able to bind the heavy but not the light chain of reduced and alkylated activated FXI (FXIa). The activation of purified FXI by activated bovine factor XII (FXIIa), a reaction independent of high molecular weight kininogen (HK), was not inhibited by either antibody. The active site on the FXIa light chain was unaffected by either patient's IgG, as measured by its amidolytic activity. In contrast, one antibody (Baltimore) or its Fab' blocked the surface-mediated proteolytic activation of FXI by human FXIIa in a concentration-dependent fashion by preventing its binding to HK, but had no effect on the rate of activation of FIX by FXIa. In contrast, the other antibody (Winston-Salem) or its Fab' inhibited the activation of FIX by FXIa in a concentration-dependent fashion but did not inhibit binding of FXI to HK. We conclude that each of these two naturally occurring antibodies is directed against a specific, separate, and distinct epitope located in the heavy chain of FXIa, one near or at the domain essential for the activation of FIX by FXIa and the other close to the domain required for binding to HK.

Amides

Amniotic fluid and advances in prenatal diagnosis.

Maternal blood, amniotic fluid, and chorionic villus samples may be evaluated in the prenatal detection of neural tube defects, cytogenetic disorders, and inborn errors of metabolism. Laboratory tests for these abnormalities usually involve very specialized methods. They should be accompanied by equally rigorous clinical follow-up methods and expert counseling.

Adult

Pathways of urinary backflow in obstructive uropathy. Demonstration by pigmented gelatin injection and Tamm-Horsfall uromucoprotein markers.

The exact pathways of urinary reflux into the renal veins were studied in four cases of clinical obstructive uropathy and in 50 normal human cadaver kidneys. In the four clinical cases Tamm-Horsfall uromucoprotein was used as a marker for location of urine. Routine light microscopy and indirect immunofluorescence for Tamm-Horsfall uromucoprotein using rabbit antiserum showed tubular backflow up to the glomerulus. Dilated tubules filled with Tamm-Horsfall uromucoprotein ruptured into thin walled veins, forming tubulovenous anastomoses with extrusion of their contents into veins. The uromucoprotein was present in interlobar and arcuate veins with superimposed thrombosis and thrombophlebitis. Injection studies using pigmented gelatin in 45 normal cadaver kidneys and pigmented vinylite with corrosion casts in five additional kidneys complemented the clinical studies. Two types of urovascular communication were produced: the less frequent direct pyelovenous communication between a rupturing fornix and an adjacent small vein, and the more common indirect pyelovenous communication in which a ruptured fornix produced a sinus extravasate, which extended along the perivenous spaces of interlobar and arcuate veins. This extravasate gained access into the veins at points of rupture where venous tributaries joined the major veins in the renal medulla. The clinical implications of these tubulovenous and pyelovenous pathways of urinary reflux include backflow of whole urine and continued nephronic function in obstructive uropathy, "reverse backflow" of blood and hematuria, and a direct access for infectious agents into the circulation. These channels provide anatomic correlates for radiologic findings of extravasates and some backflow patterns of contrast material in pyelograms of clinical obstructive uropathy. The possible immunologic consequences of refluxing Tamm-Horsfall uromucoprotein gaining access to tissues and circulation are speculative.

Adult

A prospective evaluation of placental lactogen as a test for neonatal risk.

This study evaluates the usefulness of maternal serum concentrations of human placental lactogen in the management of high-risk pregnancies. The study was performed in a community hospital over a year's time and involved 250 gestations. The test detected only 11.4% of the pregnancies defined as high-risk by clinical criteria and none of the pregnancies in which the newborn was compromised. Serum human placental lactogen is an insensitive test in predicting the outcome of pregnancies in an obstetric population unless historical information regarding maternal disease is unavailable.

Female

Ectopic ACTH, prostatic oat cell carcinoma, and marked hypernatremia.

Locally recurrent, poorly differentiated carcinoma of the prostate was associated with hypokalemic alkalosis, marked hypernatremia, diabetes mellitus of recent onset, and hyperosmolar syndrome. These findings, with mild hypertension, in the absence of clinical features of Cushing's syndrome, suggested an ectopic ACTH syndrome. Plasma ACTH and cortisol levels were markedly elevated, and failed to suppress in response to either low or high-dose dexamethazone administration. The patient's condition deteriorated rapidly. Autopsy findings included carcinoma extensively infiltrating the prostate with extension to the urinary bladder, and metastases confined to the pelvic nodes and soft tissues. The adrenal glands weighed 23 g and showed diffuse hyperplasia. Extract of the prostatic tumor was analyzed for ACTH and showed approximately 40 times normal plasma levels (or about 4,010 pg/g of tissue); ultrastructural features showed secretory granules consistent with ACTH content of the tumor cells. Such cells were positive when stained for ACTH by peroxidase-tagged immunochemical methods. The case fulfills all established criteria for relating excess corticosteroid production and nonpituitary tumors.

Adrenocorticotropic Hormone

Serum chloride analysis, bromide detection, and the diagnosis of bromism.

Current methods for determining serum chloride concentration vary in specificity. Laboratory detection of bromide in serum is usually dependent on spuriously high chloride values. In the absence of historical information, the chemical identification of bromide in serum may be the only diagnostic sign of bromism. Bromide may be found in as many as 1% of sera obtained from inpatients of a general hospital. Ion-selective electrodes and some thiocyanate methods for chloride analysis can be highly sensitive to bromide (interference). Chloride electrodes are also sensitive to iodide.

Aged

Evaluation of contemporary methods for serum CO2.

We evaluated and inter-compared several newer methods for CO2 analysis--titrimetric (Van Slyke), automatic titrator, continuous-flow/indicator, and coupled-enzyme procedures--with respect to accuracy, precision, specificity interferences, and management criteria. All methods studied appeared to be clinically acceptable; but precision decreased (standard deviations increased) for the last two methods in above-normal ranges.

Autoanalysis

Comparison of five methods for preparing blood smears.

An extensive study was undertaken to compare five methods of blood smear preparation. Three mechanical devices for preparing blood smears were compared to the traditional coverslip and manual wedge methods. A series of five slides was prepared from each sample of blood. One hundred-cell leukocyte differential counts, red cell morphology, and platelet distribution were compared. Differential counts along the axis and margins of each slide failed to reveal any significant distribution difference by method. On the other hand, there were a significantly fewer neutrophils as well as higher lymphocyte counts on the two spinner preparations. Subsequent analysis suggested that spinner preparations create more smudge cells in smears of normal and granulocytic leukemia patients, and significantly fewer smudge cells in smears of lymphocytic leukemia patients. Both spinner methods produced significant increases in erythrocytic target cells, spherocytes, and cells with shifted pallor; and significantly fewer burr cells and ovalocytes, as compared to the reference methods. The mechanical wedge device was most similar to both reference methods. Of the two reference methods, the cumbersome coverslip preparation apparently offers no practical advantage over wedge methods.

Analysis of Variance

A rapid, manual test for amylase at 52C.

A simple modification of an alpha-amylase (E.C. 3.2.1.1.) procedure, using blue starch substrate, permits quantitative results after three minutes of incubation. The procedure, performed on blank, control, and unknown speciemns, takes advantage of the heat stability of the enzyme and provides immediate and reliable data for acutely ill patients. The performance characteristics of the test on serum and urine are described. The method is distinctly advantageous in prividing rapid results for serum amylase, urine amylase, and amylase clearance in patients with suspected pancreatitis.

Amylases

Hyposplenic, coagulopathic, cryptogenetic pneumococcemia.

An unusual case of sudden, fulminant pneumococcemia and disseminated intravascular coagulation occurred in a woman who had had incidental splenectomy 8 months previously, at the time of gastrectomy for duodenal ulcer. Similar cases in which there is constant relationship of splenectomy, pneumococcal sepsis, and Waterhouse-Friderichsen syndrome have been documented. Other similarities which are notable are a tendency for the disease to occur in women, lack of a nidus of infection, and proliferation of diplococci to numbers great enough to be seen easily on the peripheral blood smear.

Adrenal Gland Diseases