Alloimmunization to the D antigen by a patient with weak D type 21.

Antibodies of apparent D specificity may be found in D+ patients. We report a D+, multi-transfused Caucasian woman with myelodysplasia who exhibited several alloantibodies. One antibody was a moderately strong (2+) anti-D that persisted for 9 months, until the woman died. Molecular analysis of the patient's RHD gene identified the rare weak D type 21 (938C > T) allele. D alloantibodies do not occur in patients with most weak D types, but some patients with a weak D phenotype, including those with type 21, can produce antibodies to nonself epitopes of the wild-type D antigen.

Chyloperitoneum in a peritoneal dialysis patient.

A woman with end-stage renal disease underwent peritoneal dialysis. On initiation of treatment, there was turbid peritoneal dialysis fluid, which proved to be of chylous rather than inflammatory origin. A low-fat and medium-chain triglycerides diet induced visible clearing of the fluid and a decrease in its triglyceride concentration. Challenge with a high-fat diet produced two early recurrences. After 8 months, dietary fat no longer induced chyloperitoneum. The patient was able to continue peritoneal dialysis at home without a recurrence.

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.

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.

Disposables as sources of preanalytical contamination and misdiagnosis.

Laboratory samples from two different patients produced false-positive results. Investigations indicated that the errors were produced by a combination of miniscule preanalytical contamination of disposables, suboptimal systems design, and very sensitive analytical systems. The errors may be avoidable by changing the configuration of workstations.

Group-specific component (Gc) alleles among Haitian immigrants.

Gc allele frequencies were determined in Haitian immigrants, a group at high risk for AIDS. Gc2, an allele associated with disease resistance, is infrequent in this group; Gc1f is frequent.

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.

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.

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.

Kell alloimmunization, hemolytic disease of the newborn, and perinatal management.

The relative frequency of Kell (K:1) antibodies in pregnant women and a series of cases of Kell hemolytic disease of newborns were evaluated to review the strategy of managing potential disease. Among reproductive-aged women, Kell antibodies are about 60% as frequent as Rho (D) antibodies, but Kell disease is only 3% as common as Rho hemolytic disease. The reason is related to frequent transfusion-alloimmunization by Kell antigen and the low frequency of the K:1 gene among fathers. Kell hemolysis is severe in about half of cases. Amniocentesis is indicated in only a few circumstances: previous child with erythroblastosis fetalis, significant increase in maternal Coombs titer, presence of Kell antigen in the father, and after comparison of the relative risks of hemolytic disease and amniocentesis in each patient. Screening for Kell antigen before transfusing premenopausal women would be a means of avoiding erythroblastosis, but the rarity of severe disease does not justify this approach.

Alloimmunization by hr'(c), hemolytic disease of newborns, and perinatal management.

A study was made of hr'(c) hemolytic disease to determine its natural history and to develop criteria for its management. Anti-c is 0.52 as frequent as anti-D(Rho) in gravid women. Seventy-four percent of infants born of c-alloimmunized women mated to c-positive men show serologic evidence of hemolytic disease of newborns. Up to 40% of affected infants require transfusion. There is evidence that ABO incompatibility between mother and fetus protects against alloimmunization. Although alloimmunization is frequently related to fetomaternal bleeding, severe hemolytic disease appears to be associated with previous maternal transfusion. Maternal antiglobulin titers of less than 1:16 are usually associated with mild disease or none at all. Women with higher titers, whose mates are hr'(c)-antigen positive, are candidates for amniotic fluid pigment analysis.

The manipulation of potassium efflux during fluoride intoxication: implications for therapy.

Based on findings in 2 fluoride-toxic patients, it was suspected that hyperkalemia played a clinically important role in the etiology of sudden death from fluoride poisoning. Using fluoridated human erythrocytes as an in vitro model, it was confirmed that fluoride produced a marked potassium efflux from intact cells. Further, neither glucose and insulin in pharmacologic doses, nor various buffers could halt the efflux by shifting the potassium intracellularly. If these results can be extrapolated to the clinical situation, removal of potassium and fluoride via exchange resins or dialysis remains the only reasonable approach to this life threatening problem. Aside from sudden hyperkalemia and hypocalcemia, no serologic marker for fluoride toxicity has been identified. A high degree of clinical suspicion is therefore essential to the diagnosis.

Hospital laboratory inventory management.

Standard business inventory procedures can be cost effective when they are adapted to hospital laboratory inventory management in a 500-bed hospital. The investment in a central laboratory store-room and one additional employee yields financial benefits and indirect service benefits. The system requires consistent use of simple procedures throughout the laboratory, and can be coupled with improved strategies for purchasing supplies.

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 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.

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.

Erythrocyte Fy antigen phenotyping helps differentiate so-called benign tertian malarias.

Isolated cases of malaria are increasing in frequency in nonendemic countries. Blood film examination remains a mainstay of diagnosis of these sporadic cases because immunologic and molecular methods are unavailable, expensive, and problematic. Two tertian malarial species, Plasmodium vivax and Plasmodium ovale, may appear to be similar morphologically. Plasmodium ovale infection is infrequent, and misdiagnosis of this species is common. Plasmodium vivax infection can be ruled out, however, if a patient's erythrocytes phenotype as Fy(a-b-), because these cells completely resist entry by the latter species.

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.