DNA replication sequence in a dicentric (functionally monocentric) X chromosome formed by the joining of two X chromosomes at region p22.

In this study we used densitometry to evaluate DNA replication kinetics in a rearranged chromosome formed by the joining of two X chromosomes at region p22. No 45X mosaicism is present in peripheral blood or fibroblast cultures. The patient has primary amenorrhea, short stature, and gonadal dysgenesis. The sequence of replication in the majority of cells is p11, q11, q13, q22-24, q12, p22, q26, q28, q27, q25, and p21, q21. Thus p11 is the earliest region to replicate, and q21 is the last. In 66% of 127 cells analyzed, the replication pattern is asymmetric, and bands q12, q26, and q28 are most likely to be out of phase on the two sides of the breakpoint. We find that band p22 has a delay of replication compared to an abnormal X derived from two X chromosomes joined at the q23 region previously reported by us. Structural rearrangement may therefore delay replication in the region of the break.

Gonadoblastoma in a true hermaphrodite with a 46,XX karyotype.

Gonadoblastomas arise in dysgenetic gonads of individual possessing a Y chromosome in their karyotype. This is the first report of a gonadoblastoma in a 46,XX true hermaphrodite.

True hermaphroditism with peripheral blood and gonadal karyotyping.

Eight documented cases of true hermaphroditism have been seen in the reproductive endocrine unit at the Medical College of Georgia since 1969. There was histologic evidence of both ovarian and testicular tissue in all cases. Seven patients had peripheral blood karyotypes: 6 had normal 46,XX peripheral blood karyotypes, and 1 patient had a normal 46,XY blood karyotype. Four of the 7 patients studied had chromosomal analysis of 1 or both gonads. Five gonads were karyotyped as 46,XX and 1 revealed a mosaic gonadal pattern of 46,XX/46,XY. The clinical features, anatomic findings, and cytogenetic studies of these patients are reviewed. Discordant findings in peripheral blood and gonadal chromosomes are discussed.

Ovarian and peripheral venous steroids in XY gonadal dysgenesis and gonadoblastoma.

Determinations of multiple steroids were made on ovarian and peripheral blood in a 46,XY patient with bilateral gonadoblastoma. The right gonadoblastoma had undergone complete calcific ablation. The principal viable cellular elements in the left gonadoblastoma were Leydig cells. Except for a borderline increase over peripheral levels of estradiol, the degenerated right tumor mass showed no evidence of endocrine activity. Venous blood emanating from the left cellular gonadoblastoma exhibited significant elevations of testosterone, progesterone, and estradiol as compared to peripheral blood. Viable sex cord elements were present in the left tumor mass but did not exhibit sufficient steroid activity to have demonstrable clinical manifestations.

Etiologies and subsequent reproductive performance of 100 couples with recurrent abortion.

From 1958 through 1977, 100 couples with documented recurrent reproductive failure were evaluated in the reproductive endocrine unit of the Medical College of Georgia. All couples underwent cytogenetic studies, radiologic evaluation of the Müllerian system, and timed endometrial biopsy. Recurrent pregnancy wastage was found to be associated with genetic disorders in 25 couples. Müllerian anomalies in 15, endocrine anomalies in 23, and negative findings in 37. The subsequent reproductive performance of each group is reviewed.

Cytogenetic findings in fifty-five couples with recurrent fetal wastage.

Balanced chromosomal translocations in parents and Müllerian abnormalities constitute defined causes of reproductive wastage. Fifty-nine couples with histories of recurrent abortion with or without fetal malformations were evaluated with cytogenetic studies and gynecography. In 44 of the couples with pure abortion histories of two or more spontaneous abortions, three (6.8%) balanced carrier parents were identified. In 11 couples with a mixed history of abortion plus fetal malformation, 3 (27.3%) had balanced translocations in one of the parents. The over-all incidence of Müllerian abnormalities in the group of 59 patients was 11.9%.

Twins discordant for 46,XX gonadal dysgenesis.

This case report describes twin sisters, one with rudimentary streak gonads and the other with normal ovarian function. Both siblings had normal 46, XX karyotypes, and zygosity testing indicated that they were identical twins. Discordance of identical twins for 46, XX pure gonadal dysgenesis suggests that environmental factors may be a causative factor in some of the karyotypically normal 46,XX forms of gonadal dysgenesis.

A cytogenetic and endocrinologic study of a set of monozygotic isokaryotic 45,X/46,XY twins discordant for phenotypic sex: mosaicism versus chimerism.

Newborn monozygotic twins with phenotypic sexual discordance were diagnosed with 45,X/46,XY gonadal dysgenesis. Cytogenetic studies of peripheral blood (serial), skin, and gonad were performed. Serial comparative gonadotropin data and luteinizing hormone-releasing hormone stimulation tests were obtained. A phenotypically normal male twin was found to have a significant number of 45,X cells only in lymphocytes and was considered endocrinologically intact. The sexually ambiguous twin sister demonstrated a significant number of 45,X cell lines in all tissues and was considered endocrinologically agonadal. These data demonstrate the role of the 45,X karyotype on abnormal gonadal formation and function and make possible different etiologies for the 45,X cell line in both twins. While mosaicism is likely for both, chimerism is possible for the normal male.

Phenotypic and cytogenetic findings in eighty-two patients with ovarian failure--changing trends.

Eighty-two patients with primary ovarian failure were evaluated clinically and cytogenetically. Sex chromosome privations were present in 52 individuals (chromosomally incompetent ovarian failure [CIOF]). A normal chromosomal constitution was present in 30 individuals (chromosomally competent ovarian failure [CCOF]). Limited estrogenic function (menses) occurred in 11.5% of the CIOF group and 40% of the CCOF group. The phenotypic features of each group are detailed in relation to chromosomal constitution, stature, estrogenic ridge function, incidence of dysgenetic tumors, and cardiovascular renal malformations. The increasing percentage of patients with CCOF due to possible diverse etiologies is noted and discussed.

A clinical and cytogenetic study of fifteen patients with 45,X/46XY gonadal dysgenesis.

The cytogenetic and phenotypic findings in 15 patients with 45,X/46,XY mosaicism are described. Six patients presented with delayed sexual development without masculinization. The remaining nine patients had varying degrees of masculinization, ranging from clitoromegaly to hypospadic male phenotypes. Cardiovascular/renal anomalies were detected in 2 of the 15 patients. Gonadoblastomas were present in two patients and did not appear to correlate with the degree of masculinization or percentage of 46,XY cells present. Structural Y chromosome abnormalities were seen in three of the 45,X/46,XY probands. MZ twinning occurred in one of the 45,X/46,XY sibships.

Use of deoxyribonucleic acid probes to test for Yq11 deletions in males with spermatogenic arrest.

A cytogenetically detectable deletion in the area of Yq11 has been demonstrated in some men with spermatogenic arrest, leading to the suggestion that a spermatogenic factor(s) lies within this region. The probe pAS1 detects an argininosuccinate synthetase pseudogene 6 (ASSP6), which has been mapped to Ycen-q11. The 4B-2 (DYS 15) probe detects a single-copy 3.3 kb EcoRI fragment that maps to the proximal portion of the Y long arm located distal to the sequence detected by the pAS1 probe. Deoxyribonucleic acid (DNA) samples from normal males and females and ten males with spermatogenic arrest were digested with the restriction endonuclease EcoRI, electrophoresed on agarose gels, Southern blotted, and hybridized with the pAS1 and 4B-2 probes. All males tested, including the ten azoospermic males with spermatogenic arrest, exhibited 4.3 kb and 3.3 kb male specific fragments with the pAS1 and 4B-2 probes, respectively. From preliminary analyses, the authors conclude that the regions detected by these two probes are not absent in these azoospermic males and that the cause of their spermatogenic arrest may not involve deletion within this region. Molecular defects affecting spermatogenesis may involve loss of sequences at Yq11, which were not tested in the study, or they may derive from heterogenous causes.

How to increase efficiency in the operating room.

The key to increasing operating room efficiency is increasing productivity. Standardizing and streamlining of internal procedures reduce bottlenecks, and computers speed the flow of information so that continuous improvement of the system becomes possible. Patterns and themes can be discovered only when one sits back and listens and watches, shifting the focus from fixing problems to discovering patterns and the structures underlying them. Rethinking the system and evaluating all aspects of the care delivery cycle, abandoning the "sacred cows" of operating room practice, and creating a vision for health care in the future are essential to survival in the managed care environment.

Immunopotentiating effect of vinca alkaloids on the antibody response to sheep red blood cells in the mouse.

Evidence is presented that the vinca alkaloids (vinblastine, vincristine, and vindesine) exert an immunopotentiating effect on the antibody response to sheep red blood cells (SRBC). The primary antibody response, measured by the rosette-forming cell (RFC) and hemagglutination (HA) assays, was enhanced by vincristine and vindesine treatments. Neither drug had any effect on the secondary antibody response. Vinblastine, while having no effect on the primary response, augmented the secondary antibody response to SRBC.

Endobronchial tuberculosis in an adult.

Although endobronchial tuberculosis has been thought to be a common childhood illness, this report is of endobronchial tuberculosis in an adult, who presented with chronic cough, a normal chest radiograph, and tuberculin conversion. The lesions were discovered at bronchoscopy, which showed complete resolution when repeated after six months of antituberculous therapy.