Use of beta-human chorionic gonadotropin in gestational aging.

Quantitative radioimmunoassay (RIA) of the beta chain of human chorionic gonadotropin (B-hCG) in serum has been used to evaluate the gestational status of 99 normal early pregnancies in contrast to 29 ectopic, threatened, aborted and/or terminated cases. Quantitative measurement of serum B-hCG-RIA standardized against the second international standard (2dIS) accurately established age of normal pregnancies in utero up to but not after three weeks postconception and with an accuracy of plus or minus four days between the third and eighth week of gestation. Quantitative urinary hCG-RIA standardized against the 2dIS were not useful for gestational aging. Useful serum hCG-RIA were identically linear and parallel with the 2dIS, had negligible crossreactivity with LH, FSH and/or TSH, and had low nonspecific binding. Of 13 hCG-RIA evaluated, only assays having these latter characteristics were able to detect ectopic pregnancies, spontaneous abortions, and/or threatened pregnancies with up to 90 percent accuracy. However, some assays not standardized to the 2dIS gave over 200 percent error in hCG serum values. Thus, correct choice of quantitative B-hCG reagents is necessary for early pregnancy assessment.

Complete duplication of the uterus and cervix with a unilaterally imperforate vagina.

Complete duplication of the uterus and cervix with a unilaterally imperforate vagina must be suspected when a unilateral pelvic mass terminates in a purpuric bulge of the lateral vaginal wall in a young woman with severely progressive dysmenorrhea. Intravenous pyelography will reveal renal agenesis ipsilateral to the imperforate vagina. The prompt and accurate diagnosis of this unusual anomaly should lead to transvaginal drainage of the retained menstrual fluids prior to irreversible damage of the pelvic viscera from chronic cryptomenorrhea.

Partial vaginal agenesis with a urinary-vaginal fistula.

A patient with partial vaginal agenesis and a urinary-vaginal fistula is presented together with a review of the 12 cases reported previously. This unusual anomaly presents with cyclically recurrent hematuria; hypothetically, it results from failure of formation or canalization of the primitive vaginal plate together with partial persistence of the urogenital sinus. Surgical correction, ideally performed after puberty, requires resection of the fistula and mobilization of the apical vaginal segment for its anastomosis to the inferior vaginal pouch.

Asymmetric hyperthecosis ovarii.

Testosterone and delta4-androstenedione concentrations, in venous blood obtained by percutaneous retrograde femoral catheterization of the ovarian and adrenal veins bilaterally, demonstrated the left ovary to be the predominant secretory source of androgens in an 18-year-old virilized female. Histologic examination of the excised ovarian tissue revealed asymmetric hyperthecosis ovarii and confirmed the biochemical data. This study demonstrates the accuracy of the venous catheterization method in locating preoperatively the hypersecretory source of androgens in virilized women. The favorable postoperative clinical result emphasizes the importance of an accurate preoperative diagnosis in virilized women even in the absence of ovarian neoplasia.

Relation of glucose to alpha-fetoprotein in amniotic fluid.

A direct relationship between amniotic fluid glucose and alpha-fetoprotein (AFP) has been found between the 16th and 22nd weeks of pregnancy. This relationship is statistically significant (P less than .001) in each of the 6 gestational weeks tested, the coefficients of correlation vary from .74 to .91. The relationship between amniotic fluid AFP and another metabolite, urea nitrogen, was not significant (r = -.34), suggesting that the AFP-glucose relationship was not spurious. Absence of pregnancy-associated macroglobulins in the samples indicates that they were not contaminated by maternal serum. These data reflect an aspect of fetal metabolism or transport that should be investigated more thoroughly.

Complement fixation for study of placental-type alkaline phosphatase.

Preparations of human placental alkaline phosphatase differing in specific enzyme activities were compared by microcomplement fixation assays using monospecific antisera. While both specific enzyme activity and complement fixation units increased 15,000-fold upon purification, the ratio between these units remained constant. Separation of an alkaline phosphatase preparation into 'A' and 'B' forms by ampholine isoelectric focusing indicated that these forms also possessed the same ratio of immunoreactive enzyme protein to enzyme activity. The correspondence of complement fixation units with specific enzyme activity indicates that complement fixation with monospecific antisera can be used to analyze structural differences among alkaline phosphatase isoenzymes.

Partial purification of pemphigus-related epidermal antigens.

Epidermal antigens partially purified by either isoelectric focusing (the pH 5.2 peak) or concanavalin A (Con A) affinity chromatography react with Con A in tube precipitation reactions. Bands of identity between crude skin antigens, the Con A affinity antigens eluted with alpha-methyl glucoside and the pH 5.2 peak are formed in Ouchterlony gel with rabbit antisera (Rab) to the pH 5.2 antigen. Absorption of Rab or pemphigus antibodies (Pab) with A+ erythrocytes does not affect complement fixation reactions of Rab with the skin antigen nor abolish the ability of Pab to interact with the intercellular cement. The pH 5.2 epidermal antigens react weakly with Pab in tube precipitation reactions and only weakly, if at all, to inhibit Pab reactions in the region of the intercellular cement. High concentrations of Con A inhibit the Pab, peroxidase-anti-IgG tissue reaction whereas the converse inhibition does not occur. Simultaneous use of both Pab and Con A-perodixase reactions at Con A concentrations which do not inhibit Pab, causes enhanced tissue peroxidase reactions in the region of the intercellular cement. These preliminary data indicate that the Pab and Con A-reacting sites are localized on different molecules or antigenic determinants in the intercellular cement. They exclude the possibility that A-blood substances are involved in either site.

The emerging role of carcinodevelopmental antigens in the clinical laboratory.

Patterns of carcinoembryonic antigens (CEA) in fetal gut, seminal plasma, and amniotic fluids were investigated. In fetal gut the broadest range of CEA-expression occurred during the period of maximal mucosal differentiation. While normal adult colon or other fetal stages expressed lower quantitative and qualitative amounts of CEA, maximal CEA expression could be found in a pool of 20 primary adenocarcinomas of the colon. Low levels of CEA in seminal plasma were associated with subfertile, poorly differentiated sperm as opposed to CEA levels found in either normal ejaculates or those obtained from vasectomized, previously fertile males. In amniotic fluid CEA remained at a constant level between the 16th and 22nd week in utero as did fructose and urea levels. Glucose and histaminase levels showed great variance. The relationship of these latter findings to genetic defects is currently being investigated. These data suggest that an ever increasing number of biologic samples will be tested in the clinical laboratories for carcinodevelopmental antigen levels. These will be used for the prognosis and/or diagnosis of abnormal differentiation patterns in patients with cancer or in the developing fetus.

Gene activation of molecules with carcinoembryonic antigen determinants in fetal development and in adenocarcinoma of the colon.

"Fingerprints" of 0.9% NaCl solution extracts obtained from fetal guts and individual adenocarcinoma of the colon show a randomized pattern of expression of carcinoembryonic antigen (CEA) determinants by CEA radioimmunoassay and isoelectric focusing. All CEA-containing antigens found in a pool of 20 primary adenomas were found at some stage in fetal development. No single CEA-reacting peak was typical of any one period of fetal development. When fetal gut profiles were grouped according to trimester in utero, however, an expanded gene pool was found in the second trimester which correlates well with maximum gastrointestinal growth and differentiation. Isoelectric focusing-CEA radioimmunoassay profiles of individual primary adenomas were similar to but never identical with individual fetal gut profiles. "Fingerprints" of metastatic adenomas of entodermal origin showed quantitative and qualitative increases in molecules with CEA determinants unlike these latter categories. Such data suggest that both integrator and controller gene activities may be lost in metastatic disease. Rather than "phase-specific gene sets" on different chromosomes being activated by various oncogenic modalities, it is more probable that individual chromosomes are involved in oncogenesis. While more data are needed to confirm this idea, it is safe to say that the expression of molecules with CEA determinants need not be caused by either derepressive or reexpressive gene activation. These data point to the individuality of gene expression of molecules with CEA determinants both in fetal development and in early neoplasia. Since CEA-reacting molecules were not found in tumors of ectodermal or mesodermal origin by these methods, such products should be termed carcino-developmental antigens of entodermal or colonic origin.

Circulating carcinoembryonic antigen (CEA): relationship to clinical status of patients with inflammatory bowel disease.

Plasma levels of circulating carcinoembryonic antigen (CEA) were measured by zirconyl phosphate gel radioimmunoassay in 112 patients with chronic inflammatory bowel disease. The levels were then related to category, extent, duration, and severity of disease, as well as to the ages and surgical status of the patients. The distribution of CEA levels and their mean values were significantly raised over the levels in 33 normal control subjects, and were similar among patients with ulcerative colitis compared with those with granulomatous bowel disease. Positive values were defined as those in excess of 2.5 ng/ml. Positive assays occurred in 42% of ulcerative colitis patients, in 38% of Crohn's disease patients, and in 40% of the total group with inflammatory bowel disease. Among normal control subjects, only 3% were positive. Among inflammatory bowel disease patients, positive CEA assays occurred more frequently with more severe disease, more extensive anatomical involvement, younger ages, and shorter duration of disease. Those patients who had undergone total colectomy showed levels of circulating CEA and frequency of CEA positivity similar to those of an age-matched normal control group. Levels of CEA did not correspond with known cancer risk factors in patients with inflammatory bowel disease. Although rising or persisting plasma CEA values unrelated to severity and extent of disease may indicate an unfavourable prognosis in cancer, this study shows that a single CEA value in patients with chronic inflammatory bowel disease is not a reliable indicator of cancer risk.

Immunotherapy of the Dunning leukaemia with thymic extracts.

Injections of thymic extract (TE), TE primed lymphocytes or normal lymph node cells were effective in bringing about total remission of the Dunning leukaemia in inbred Fisher CD rats. Survival greater than 365 days occurred in 10-80% of the various treated groups whereas untreated leukaemic rats, or leukaemic rats treated with spleen "mock thymus extract" or bovine serum albumin, died within an average of 10-17 days. Administration of antilymphocyte serum into leukaemic rats enhanced their death rate. Stimulation of cell mediated immunity via the production of functional thymus stimulated lymphocytes is postulated as the mechanism by which tumour rejection occurred.