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.

Absence of the testicular determining factor gene SRY in XX true hermaphrodites and presence of this locus in most subjects with gonadal dysgenesis caused by Y aneuploidy.

OBJECTIVES: The purpose of our study was to discover whether the testicular determining factor gene SRY (sex-determining region on Y) is present or absent in XX true hermaphrodites and in subjects with gonadal dysgenesis caused by Y aneuploidy. STUDY DESIGN: We screened five XX true hermaphrodites and 24 subjects with gonadal dysgenesis caused by Y aneuploidy for the presence or absence of SRY. With the polymerase chain reaction technique, the sequence coding the 80 amino acid-conserved motif was amplified. The 0.9 kb Hincll pY53.3 subclone, which covers the open reading frame of SRY, serves as a probe for Southern blot analysis. RESULTS: Test results for all five XX true hermaphrodites were negative for SRY. Conversely, 22 of the 24 individuals with 45,X/46,XY gonadal dysgenesis were positive for SRY, including the 10 subjects with only bilateral streak gonads. CONCLUSIONS: The absence of SRY in XX true hemaphrodites and the presence of SRY in 10 subjects with 45,X/46,XY constitution who harbored only bilateral streak gonads seem to indicate that multiple genes are involved in gonadal differentiation.

Correlation of the testicular determinant factor sequence zinc finger Y with varying gonadal phenotypes in a series of 13 subjects with gonadal dysgenesis due to Y aneuploidy.

Deoxyribonucleic acid samples from a series of 13 subjects with 45,X/46,X,altered Y, and varying gonadal phenotypes (streak-streak, n = 9; streak-testis, n = 2; testis-testis, n = 2) were analyzed for the presence of the candidate testicular determinant factor sequence zinc finger Y. The Y-specific probes Y97 mapped to Y centromere, pDP105 A,B mapped to Yp and distal Yq11, respectively, hybridized with the deoxyribonucleic acid from all the 13 study subjects. The same deoxyribonucleic acid samples were analyzed for the presence of the zinc finger Y sequence. Eleven of the 13 subjects were positive for the zinc finger Y sequence. Four zinc finger Y-positive subjects had unilateral (n = 2) or bilateral (n = 2) testicular differentiation. Among the nine subjects with bilateral streak gonads, seven showed the presence of this sequence. The lack of testicular differentiation in the presence of quantitatively normal or almost normal zinc finger Y bands could not be explained by mosaicism alone. Mutations not detectable by analysis with the method of Southern with pDP1007, may occur in the testicular determinant factor gene vitiating testicular development.

Use of human alpha-satellite deoxyribonucleic acid to detect Y-specific centromeric sequences.

The Y alphoid deoxyribonucleic acid probe Y97 has proved to be specific for the human Y centromere and to define a Y-specific 5.5 kb Eco RI fragment. Three experiments were designed to evaluate the sensitivity and the specificity of this Y alphoid probe Y97. In the first experiment the centromeric Y-specific 5.5 kb Eco RI fragment was clearly seen in the mixture of 0.050 microgram of male DNA with 4.950 micrograms of female DNA (1%). In the second experiment the same dilutional study was applied to the Yq11-related probe 4B-2 for comparison purpose. In the third experiment, hybridization with the Y97 probe was performed on 20 subjects with mosaic cell lines containing a cytogenetically identifiable Y (n = 10) and a cytogenetically unidentifiable minute (n = 10) fragment. Nineteen of the 20 subjects demonstrated the Y-specific 5.5 kb Eco RI hybridization band with the centromeric Y97 probe. These experiments demonstrated the utility of the Y97 probe to consistently identify cytogenetically altered Y chromosome fragments and confirm the mapping of the alphoid repeat sequences to the centromeric region of the Y chromosome.

Ring chromosome 5.

A case of an infant with ring chromosome 5 is presented. The phenotype of this patient and other reported cases is analyzed with respect to the deletion of the long arm of chromosome 5.

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.

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.

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.

Use of two different deoxyribonucleic acid probes to detect Y chromosome deoxyribonucleic acid in subjects with normal and altered Y chromosomes.

Four experiments evaluated the sensitivity and specificity of molecular techniques to detect human Y chromosome deoxyribonucleic acid. In experiment I, electrophoretic separation of normal male deoxyribonucleic acid fragments after digestion with endonuclease Hae III revealed two male-specific bands of 3.4 and 2.1 kilobase (kb). These bands were not visible if the fraction of male deoxyribonucleic acid in mixed samples was less than 0.3. In experiment II, by means of a repetitive copy Y deoxyribonucleic acid probe (pS4) mapped to Yq12, a male-specific 2.3 kb band was detectable in mixtures of 2.5 ng of male deoxyribonucleic acid and 997.5 ng of 45,X female deoxyribonucleic acid. In experiment III, hybridization with the pS4 probe was performed on the deoxyribonucleic acid of 20 subjects with a normal or a variant Y chromosome. In experiment IV, deoxyribonucleic acid from the same subjects was hybridized to a single copy probe (4B-2) mapped to the Yq11 region. Deoxyribonucleic acid from category A subjects (n = 8) with cytologically normal Y chromosomes hybridized to both deoxyribonucleic acid probes. Deoxyribonucleic acid from category B subjects (n = 2), including a variant Y chromosome that was negative for Q-banding but positive for C-bands, hybridized with the distal pS4 and proximal 4B-2 probes. Deoxyribonucleic acid from category C subjects (n = 10) with variant Y chromosomes uniformly negative for Q- and C-bands, did not hybridize with the pS4 probe. Deoxyribonucleic acid from three of the 10 category C subjects did hybridize to the more proximal sequence-detecting 4B-2 probe. Deoxyribonucleic acid from the remaining seven subjects in category C did not hybridize with either of the deoxyribonucleic acid probes.

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.

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.

Delayed sexual development: a study of 252 patients.

A series of 252 patients with abnormalities of pubertal development are reported. Ovarian failure, followed by Rokitansky syndrome and then physiologic delay, are the most frequently encountered etiologies. Other etiologies are diverse and numerically less frequent. The average age of presentation, patient's height, somatic anomalies, diagnostic errors, and subsequent reproductive potential of each diagnostic group are reported. Only 35 (14%) of all patients presenting with abnormalities of pubertal development had subsequent normal reproductive potential. All of these patients were in the physiologic delay category.

Prenatal chromosomal diagnosis. Racial and geographic variation for older women in Georgia.

In a study of Georgia women aged 40 years and older, 15% made use of prenatal chromosomal diagnosis. There was, however, substantial racial and geographic variation, ranging from a use ratio of 60% among whites in two large urban counties to 0.5% among blacks outside Augusta and Atlanta health districts. This simple population-based epidemiologic analysis suggests that future program planning for genetic services in Georgia should address ways to increase access by rural women, especially blacks. Similar analyses in other states could be used for planning genetic services.

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.

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.

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.

Gonadal dysgenesis.

The spectrum of patients with gonadal dysgenesis has expanded over the last decade to include cytogenetically normal individuals. Comprehension of the etiology of gonadal maldevelopment in these patients remains tenuous. More careful study of pedigrees involving 46, XX and 46, XY gonadal dysgenesis may provide better understanding of the mechanism of ovarian failure in these individuals. An important approach will be to identify other disorders occurring in conjunction with primary ovarian failure that can serve as genetic markers for linkage studies. The next decade must provide information that transcends gross structural alterations in sex chromosomes.