Managing depression in outpatients.
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Biomedical subjects
Publications and source records attributed to G E Sarto.
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Between 1996 and 1999, 18 academic health centers were awarded the designation of National Center of Excellence (CoE) in Women's Health by the Office on Women's Health within the Department of Health and Human Services and were provided with seed monies to develop model clinical services for women. Although the model has evolved in various forms, core characteristics that each nationally designated CoE has adopted include comprehensive, women-friendly, women-focused, women-relevant, integrated, multidisciplinary care. The permanent success of these comprehensive clinical programs resides in the ability to garner support of leaders of the academic health centers who understand both the importance of multidisciplinary programs to the clinical care they provide women and the education they offer to the future providers of women's healthcare.
The American Academy of Neurology and the American College of Obstetricians and Gynecologists recently issued practice parameters for women with epilepsy. These parameters suggest optimal care practices. To assess knowledge of the issues covered in the parameters and to facilitate educational efforts to promote best care, the Epilepsy Foundation conducted a survey of healthcare professionals likely to provide care to women with epilepsy. The survey sampled 3535 healthcare professionals across a wide range of specialties. Most respondents did not know the specific effects of estrogen and progesterone on the seizure threshold, were not aware of menstrual-associated seizure patterns, and could not identify which antiepileptic drugs interfere with oral contraceptives. The majority of respondents did not know that women with epilepsy have higher rates of infertility, reproductive endocrine disorders, and sexual dysfunction. Most respondents did not know the frequency of birth defects in children born to women with epilepsy. Providers seeing the largest number of persons with epilepsy were more likely to have correct answers. By specialty, neurologists provided the highest number of correct responses, followed (in descending order) by endocrinologists, obstetricians/gynecologists, internal medicine physicians, family practice physicians, and pediatricians. These results suggest that women with epilepsy are not receiving adequate counseling and that care practices may not conform to those recommended.
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OBJECTIVE: To assess clinical competency of third-year medical students completing a problem-oriented, primary care emphasis clerkship in obstetrics and gynecology using an objective structured clinical examination, and to determine the feasibility of implementing the objective structured clinical examination in the curriculum. METHODS: Sixteen groups of third-year medical students were evaluated prospectively on their exit performances with a six-station objective structured clinical examination designed to test clinical competency in basic primary care obstetrics-gynecology. Consistency of scores across stations, differences in performance for separate groups, and relationship of objective structured clinical examination scores compared with other indicators of medical proficiency, such as written examinations and faculty evaluations, were assessed. RESULTS: One hundred ninety-eight students were evaluated over 25 months. Test reliability across stations revealed alpha values ranging between .50 and .56. Correlations between performance on the objective structured clinical examination and the written test (r = .10) were low, demonstrating that the objective structured clinical examination clearly tests a separate domain of student capability. Cost of the objective structured clinical examination was $81.66 per student. CONCLUSION: The objective structured clinical examination is a reliable and valid test of the clinical competence of medical students in the primary health care of women. It provides information that is not obtained by more traditional assessment modalities at a reasonable cost.
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Recombinant 8 syndrome is a well-established syndrome with mental and developmental retardation and usually severe cardiac anomalies. A carrier parent will produce affected offspring in 6% of pregnancies and carrier offspring in 53% of such pregnancies. Four New Mexican kindres ascertained by the discovery of four apparently unrelated probands with cytogenetically confirmed recombinant 8 syndrome were studied. We found that (1) recombinant 8 syndrome will soon no longer be confined to New Mexico and southern Colorado, (2) the number of persons at risk may be higher than previously considered, and (3) through proper pedigree techniques and increased professional education, most carriers can be identified.
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The chromosome replication pattern of a man with 49,XXXXY was analyzed using 3H-thymidine and autoradiography as well as BrdU and acridine orange. The former technique showed a highly irregular replication pattern; the latter revealed one early replicating X chromosome, and the other three more or less asynchronously replicating. Two hypotheses seem to explain best the abnormal phenotype of males with an XXXXY sex chromosome constitution: The number of the always active regions (tip of Xp) and of the possibly always active regions (the Q-dark regions on both sides of the centromere) is increased from one to four. The replication pattern of the late-replicating X chromosomes is highly asynchronous, which might affect the phenotype. The possibility that more than one X chromosome might remain active in some cells, an even more abnormal and obviously deleterious situation, is still open.
Cases of autosomal trisomy and trisomy mosaicism among liveborn infants are reviewed, and a second case of chromosome 3 trisomy mosaicism is described. The occurrence of autosomal trisomy for a particular chromosome is in general negatively correlated with the number of genes which have been localized to that chromosome. It is also positively related to the Q-brightness of the chromosome, which reflects its content of intercalary heterochromatin. Furthermore there are significantly fewer autosomal trisomics for chromosomes which contain hot spots for mitotic chiasmata in Bloom syndrome (chromosomes 1, 3, 6, 11, 12, 17, 19, and 22), compared with similar-sized control chromosomes 2, 4, 7, 9, 10, 18, 20, and 21. This is interpreted as further evidence for the gene richness of the hot spots which, being active, are extended in interphase and are therefore available for mitotic crossing over. The gene richness of these short Q-dark regions is also borne out by the scarcity of trisomic abortions for the chromosomes involved (the embryo dies before the abortion is recognized) and by the higher number of genes localized to these chromosomes compared with the control chromosomes.
Segregation after mitotic crossing-over in an isodicentric (idic) X chromosome with one active and one inactive centromere has given rise to two new cell lines, one in which the idic(Xpter) chromosome has two active centromeres (most of these chromosomes also have an inversion) and another in which neither centromere is active. The two X chromosomes are attached at the telomeres of their short arms. Similar segregation has given rise to two other cell lines with idic(Xq-) chromosomes. Other observations on segregation after mitotic crossing-over are reviewed. Unequal crossing-over has apparently played a major role in the evolution of various genes and heterochromatin. Retinoblastoma and Wilms tumor are in some cases associated with homozygosity of a chromosome segment resulting from mitotic crossing-over. Similarly, the high incidence of cancer in Bloom syndrome may be caused by mitotic crossing-over leading to homozygosity or amplification of oncogenes.
The course of endomitosis in human hydatidiform moles has been analyzed. It differs from the classical description of endomitosis in that endoprophase is completely missing and, very probably, so is a typical interphase. The chromosomes are even less synchronized in their replication and condensation cycle than in normal mitosis. At no point do all chromosomes decondense, but a part remains condensed while others are extended and in the process of synthesizing DNA. Even two paired sister chromosomes may replicate nonsynchronously. The latest replicating chromosome is usually a large darkly staining chromosome, which we tentatively identify as the inactive X. No DNA synthesis takes place during "endometaphase" or "endoanaphase" stages, when the chromosomes are most condensed. Some polyploid "endoanaphases" or "endotelophases" with stretched out chromosomes obviously represent end-stages of the endomitotic pathway, and the nuclei are in the process of reverting into evenly stained nuclei. In some "endometaphases," a near-haploid number of chromosomes can be counted. In others, the endochromosomes seem to be compound structures consisting of several chromosomes that have not separated during the previous endomitoses. This is seen also in normal trophoblast and cervical cancer. In large cancer cells, such bundles can be seen in the process of falling into individual chromosomes.
The origin and behavior of human dicentric chromosomes are reviewed. Most dicentrics between two nonhomologous or two homologous chromosomes (isodicentrics), which are permanent members of a chromosome complement, probably originate from segregation of an adjacent quadriradial; such configurations are the result of a chromatid translocation between two nonhomologous chromosomes, or they represent an adjacent counterpart of a mitotic chiasma. The segregation of such a quadriradial may also give rise to a cell line monosomic for the chromosome concerned (e.g., a 45, X line). Contrary to the generally held opinion, isodicentrics rarely result from an isolocal break in two chromatids followed by rejoining of sister chromatids. In this case the daughter centromeres go to opposite poles in the next anaphase, and the resulting bridge breaks at a random point. This mechanism, therefore, leads to the formation of an isodicentric chromosome only if the two centromeres are close together, or if one centromere is immediately inactivated. Observations on the origin of dicentrics in Bloom syndrome support these conclusions. One centromere is permanently inactivated in most dicentric chromosomes, and even when the dicentric breaks into two chromosomes, the centromere is not reactivated. The appearance and behavior of the "acentric" X chromosomes show that their centromeres are similarly inactivated and not prematurely divided. Two Bloom syndrome lymphocytes, one with an extra chromosome 2 and the other with an extra chromosome 7, each having an inactivated centromere, show that this can also happen in monocentric autosomes.
Nuclear morphology and DNA synthesis were analyzed to determine the mechanism through which hydatidiform moles proliferate. Hydatidiform moles are characterized by a great variation in nuclear morphology and size. There are cells with small nuclei of variable size that have chromocenters and Barr bodies which do not undergo DNA synthesis or mitosis, as well as cells in the diploid range that have evenly stained nuclei that display numerous mitoses and a high proportion of interphase nuclei in the process of DNA synthesis. Nuclei in the medium range show classical endomitotic stages. Endomitotic nuclei in endometaphase do not label with tritiated thymidine; endoanaphase nuclei may have one or a few chromosomes labeled, and endotelophase nuclei are heavily labeled. Nuclei that are evenly stained and are in the medium- to giant-size range label differently, depending upon their size. Many of the medium-sized nuclei are labeled, indicating DNA synthesis; the large nuclei are rarely labeled, and the giant nuclei are never labeled. The growth of a hydatidiform mole appears to be the result of normal mitosis and cytokinesis, as well as polyploidization and accompanying cell enlargement achieved through endomitosis and endoreduplication.
The concept and role of endomitosis is reevaluated in the light of observations on three organisms. Endomitosis which morphologically agrees with Geitler's (1939) classical definition is compared in tapetal cells of the liliaceous plant Eremurus, in the septal cells of the testicular follicles of the grasshopper Melanoplus, and in human cells from normal and molar trophoblasts and cervical cancer. These observations, together with those of Kidnadze and Istomina (1980), show that functionally at least two fundamentally different types of endomitosis exist, although morphologically the stages resemble each other in the three organisms. In the first type, exemplified by Eremurus, each endomitosis leads to a chromosome constitution which represents one level higher ploidy, a course that has been assumed to be characteristic of endomitosis in general. The second type, observed in its most characteristic form in the grasshopper, seems to be stationary: no DNA synthesis occurs, but an intensive RNA synthesis takes place. Presumably such cells have reached a final state in their development and are specialized in manufacturing one or more gene products. Endomitosis in normal placenta comes near this type, although DNA synthesis takes place in occasional cells. However, similar endomitotic nuclei in the hydatiform moles are in the process of DNA synthesis. When endomitosis is analyzed in different organisms and tissues, the observation that this process is not one entity should be kept in mind.
The structure and origin of giant nuclei in human cancer cells were studied in two cases of squamous cell carcinoma of the cervix. Feulgen-squash preparations of untreated biopsies showed the following types of nuclei: fairly evenly stained nuclei, nuclei with distinct chromocenters from which individual chromosomes sometimes seemed to radiate, and nuclei with banded structures which we tentatively interpret as some type of "polytene" chromosomes possibly showing prophase chromomeres. In neither tumor did either the small or large nuclei display any X chromatin bodies. The main processes giving rise to the different types of nuclei are endoreduplication, true endomitosis, and a kind of polytenization. The multichromosome chromocenters that fell apart possibly represent polytene chromosomes separating into individual chromosomes.
Familial aggregates of incomplete Müllerian fusion have been reported, but the role of genetic factors has not been elucidated. In the last several years, we have fortuitously encountered three families in which several members were affected with Müllerian fusion anomalies. In two families, several members had incomplete Müllerian fusion as traditionally described. In the third family, several members had the hand-foot-genital syndrome, a rare autosomal dominant disorder characterized not only by Müllerian fusion defects but also by skeletal (hand and foot) malformations. The etiologic heterogeneity of Müllerian fusion defects is considered.