Robert E. Wenk

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 Cushings 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 patients 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. Cancer 40:773–778, 1977.

Nephrogenic adenoma of the urinary bladder and urethra

The histologic and ultrastructural features of nephrogenic adenomas of the urinary bladder and urethra were studied in multiple specimens obtained from eight patients. Three of these were studied by indirect immunofluorescence for Tamm-Horsfall uromucoprotein. The lesions are uncommon benign metaplastic proliferations of urothelium, occurring most frequently in males as small cystic, papillary, or nodular masses and most often presenting with hematuria. Typically the metaplastic tubules resemble nephronic tubules. A florid atypical and pseudoinfiltrative proliferation of these tubules may led to an erroneous diagnosis of adenocarcinoma. Ultrastructural features of proximal convoluted tubules were identified in some of the tubules, but resemblance to specific segments of distal tubules was less certain. The ultrastructural features combined with the absence of Tamm-Horsfall protein in tubular lumina or cells suggest a mesonephric rather than metanephric homology. The lesions are appropriately treated by transurethral resection or fulguration, but persistent lesions were present in three patients up to 18 yeas after initial treatment.

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.

The specific power of parentage exclusion in a child's blood relatives

BACKGROUND: The impersonation of parent and child by two other blood relatives is an important problem in parentage analysis involving potential immigrants.

Population data on the forensic genetic markers: Phosphoglucomutase-1, esterase D, erythrocyte acid phosphatase and glyoxylase I

Blood specimens from white and black sample populations from Baltimore, Maryland, were analyzed for the four most forensically important, polymorphic red cell enzyme systems-phosphoglucomutase-1, esterase D, erythrocyte acid phosphatase and glyoxalase I. The distributions of the phenotypes for each marker in each racial group were in Hardy-Weinberg equilibrium. The population data were similar to previously reported data for Whites and Blacks from different geographical locations within the United States.

Laboratory evidence of unsuspected parental consanguinity among cases of disputed paternity

A search was conducted to find evidence of possible incestuous unions between the biologic parents of children involved in 2500 paternity cases. Suspicion was raised when either (1) a mother and her child possessed identical HLA phenotypes, or (2) the child appeared to be possibly homozygous for one maternal haplotype (i.e., one of the childs HLA haplotypes was a blank). These mother-child HLA-haplotype dualisms (MHDs) occurred in 5% of all cases. Frequency of exclusion of the accused men in cases demonstrating MHD, was compared with the remaining paternity cases. No significant difference was found in overall exclusion rates between MHD cases and controls when exclusion produced by HLA and red cell antigen systems were observed. However, there was a greater rate of exclusion in MHD cases when comparing exclusions produced by red cell antigen systems regardless of whether HLA tests excluded paternity (p less than 0.025). MHD cases involving teenaged mothers differed from control cases in frequency of exclusion of paternity only on the basis of red cell antigen phenotyping (p less than 0.005). The HLA systems usefulness in paternity testing is diminished when there is MHD; multiple, independently-inherited systems are relatively more useful in these circumstances. The search method detects only half of potential incest cases; proof of incest requires more extensive testing for homozygosity among other polymorphisms. Since calculations of likelihood of paternity are inappropriate in cases involving close consanguinity, detection and follow up studies are important. Data suggest that one-fifth of MHD cases may involve first degree consanguinity and that the incest rate among paternity cases may be as high as 2%.

Incest diagnosis by comparison of alleles of mother and offspring at highly heterozygous loci

Background: Methods that detect a childs homozygosity by examination of allelic products are insensitive for diagnosing incest because, at a given locus, a homozygous state is expected with a frequency of only 0.25 when parents are first‐degree relatives. Furthermore, these methods are not specific if the population contains many homozygous individuals or silent alleles that cause apparent homozygosity.

Utility of HLA and six erythrocyte antigen systems in excluding paternity among 500 disputed cases

Six erythrocyte antigen systems and the HLA system were evaluated to establish their practical value in 500 cases of disputed paternity. The actual results were very close to predicted values. HLA testing is expected to detect 92% and red cell testing is expected to detect 67% of men falsely accused in paternity suits. The findings of this study show that HLA detected 94% and red cell testing detected 69% of 107 men falsely accused in 500 paternity cases. In order of sensitivity, Rh, MNSs, and ABO were the most useful erythrocyte marker systems. There were six out of 107 cases in which exclusions would have been undetected if red cell typing had not been performed. Five of the six cases involved common HLA haplotypes.

Paternity probabilities of biologic fathers and unexcluded, falsely accused men using blood group markers

A frequent legal argument raised in defense of men accused of paternity, but not excluded by genetic tests, is that the probabilities of paternity of falsely accused men are similar to those of biologic fathers. This assertion was tested in a computer simulation experiment that used a database of 15,000 actual paternity cases to provide red cell and HLA phenotypes of mothers, children, and putative fathers. Tests had a combined probability of exclusion of 97.3 percent. Equal numbers of true and false fathers were generated from the data by computer to achieve a prior probability of paternity of 0.5. True fathers phenotypes were those of unexcluded men from actual cases (Group A) or of mothers from actual cases (Group B) in which paternity was not excluded. The false father group was created by assigning the phenotypes of racially identical men who were selected at random from among cases other than their own. Probabilities of paternity were calculated for the men in each group and were classified into descriptive intervals. The frequency of men in each group was compared in each interval. The frequency distributions of probabilities of paternity for true fathers and unexcluded, falsely accused men (false fathers) were markedly dissimilar.