Diagnosis of infective endocarditis on a Starr-Edwards prosthesis by transesophageal echocardiography.
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Biomedical subjects
Publications and source records attributed to J R Shapiro.
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Assessed the concept of the "expendable child" syndrome proposed by Sabbath (1969) as a contributing factor in adolescent suicide attempts. It was hypothesized that suicidal adolescents would be rated higher on a measure of "expendability" than would a psychiatric control group of adolescents with no known history of suicide attempts or ideation. Forty adolescents, ages 13-24, who had been seen in psychotherapy at a teen-age health clinic, were rated by their psychotherapists on suicidality and a 12-item scale of expendability (a sense of being unwanted and/or a burden on the family). As predicted, suicidal adolescents received significantly higher ratings on the expendability measure than nonsuicidal adolescents. Results support the concept that feeling expendable is a characteristic of suicidal adolescents. Implications for prevention and treatment of adolescent suicidality are discussed.
A low pressure gradient across the residual lesion and a minimal percent residual stenosis are markers of a successful coronary angioplasty. A more physiologic method of assessing the results of coronary angioplasty would involve assessment of myocardial perfusion in the affected coronary bed. Contrast two-dimensional echocardiography provides information about regional myocardial perfusion. To assess the correlation between pre- to postcoronary angioplasty changes in gradient or percent stenosis and the increase in peak contrast intensity, 23 consecutive patients were studied during coronary angioplasty. In 19 of the 23 patients, the coronary angioplasty was successful and in 15 (79%) of the 19, an adequate echocardiographic study was obtained. Mild and transient side effects of echo contrast were observed in 3 of the 15 patients. The gradient across the residual lesions decreased from 52 +/- 12 to 11 +/- 4 mm Hg (mean +/- SD), the diameter of the stenotic lesion decreased from 89 +/- 10 to 25 +/- 16% and corrected peak contrast intensity (peak contrast - baseline contrast in gray level U/pixel) increased from 15 +/- 16 to 50 +/- 26. All these differences were significant at the p less than 0.001 level. Corrected peak contrast intensity correlated exponentially with the decrease in pressure gradient (r = 0.82, p less than 0.001). The correlation curve had a greater increase in peak contrast intensity at gradient decreases greater than 45 mm Hg. Corrected peak contrast intensity did not correlate with decrease in diameter of the stenotic lesion (r = 0.19).
Normal human kidney proximal tubule cells into which a ras oncogene was inserted undergo a series of transformation-related alterations that are characteristic of renal carcinomas. These include changes in morphology, growth potential, anchorage dependence, antigen expression, growth factor production, and chromosomal stability. Further, there are spontaneous progressive alterations in vitro in the karyotype and antigenic profile of the transformed cells. Cytogenetic analyses suggest that alterations of chromosome 21 may play an early and pivotal role in the development of transformed proximal tubule cells.
Submaximal supine exercise was done by 17 patients with mitral prostheses. Eleven had Björk-Shiley (BS) and six had Starr-Edwards (SE) valves. In 15 patients with normally functioning prostheses, valve area at rest was 2.4 +/- 0.25 cm2 in the BS patients and 1.8 +/- 0.35 cm2 in the SE group (p less than 0.01). In the SE group, peak and mean gradients increased from 8 +/- 1 and 5 +/- 1 mm Hg, respectively, at rest to 22 +/- 5 and 13 +/- 4 mm Hg at peak exercise (mean +/- 1 SD). In the BS group, peak and mean gradients increased from 10 +/- 3 and 5 +/- 2 mm Hg, respectively, at rest to 16 +/- 3 and 10 +/- 3 mm Hg at peak exercise. Peak pressure gradient at peak exercise and the increase in peak gradient with exercise (exercise-resting gradient) were significantly higher in the SE group (p less than 0.05). By plotting the heart rate versus the transmitral gradient during the recovery period, a heart rate-gradient curve was obtained for each type of prosthesis. Doppler echocardiography with moderate supine exercise can be performed in most patients with mechanical prosthesis. Hemodynamic properties (the occlusive character of the SE prosthesis) were brought out by exercise. Doppler echocardiographic measurements during exercise can provide important information, particularly in patients with borderline measurements at rest.
The karyotypic and antigenic phenotypes of early passage normal and malignant glial cultures were correlated in vitro. Astrocytomas (4) were distinguished from the normal glia (8) by a mixed near-diploid karyotype and anchorage-independent growth. Malignant gliomas (41) demonstrated cytogenetic abnormalities ranging from mixed normal G- and Q-banded and near-diploid cultures, through mixed near-diploid/hyperdiploid to predominantly hyperdiploid stem-lines. This correlated with the differential expression of certain antigens and established qualitative antigenic differences from normal glia. Associations were found between histopathologic grade of glial neoplasm and the expression of antigens 5.1H11 (p = 0.0002), CNT/11 (p = 0.001), CNT/10 (p = 0.004), CAT301 (p = 0.014), M111 (p = 0.024), and L101 (p = 0.044). An ominous association was demonstrated between the duration of clinical survival and the expression of antigens 5.1H11 (p = 0.0007), CNT/10 (p = 0.027) and B2.6 (p = 0.038). Correcting for diagnosis and age, multivariate analysis demonstrated that HLA-DR (p = 0.050) and 5.1H11 (p = 0.069) were unfavorably correlated with patient survival. This suggests the application of the in vitro immunophenotype for its predictive utility, as well as a novel method of selection of tumor-associated antigens for monoclonal antibody-mediated immunotherapy.
Sonicated albumin has been proposed as a near ideal echocardiographic contrast agent with little myocardial toxicity or hemodynamic effect. Its use has not yet been reported in humans, partly because of difficulties in preparation. With use of the newly modified sonication method, 10 ml of 5% albumin was sonicated for 75 s with a 5.0 ml slow infusion of air. This resulted in microbubbles with a mean diameter (+/- SD) of 5 +/- microns). Fourteen patients undergoing routine coronary angiography were studied. One patient had normal coronary arteries; the other 13 had significant coronary artery disease. In a subgroup of nine patients, sonicated albumin and sonicated diatrizoate meglumine sodium (microbubble diameter 9 +/- 3 microns) were injected several minutes apart, using the same technique. Videodensity-time curves were obtained from a region of interest in the myocardium. Corrected peak contrast intensity (baseline contrast intensity subtracted from peak contrast intensity, gray scale U/pixel) for sonicated albumin and for sonicated diatrizoate meglumine sodium was 51 +/- 26 and 52 +/- 19, respectively (p = 0.89). Washout half-time (T1/2) for the two agents was 5.5 +/- 4.5 and 16.0 +/- 12.2 s, respectively (p = 0.01). One patient with unstable angina experienced transient chest pain after repeated albumin injections. No electrocardiographic changes, blood pressure changes or wall motion abnormalities were observed. Administered by intracoronary injection, sonicated 5% albumin is a safe and effective echocardiographic contrast agent for myocardial perfusion imaging, yielding excellent myocardial contrast with physiologic washout time.
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Perinatal lethal osteogenesis imperfecta (OI type II), a heritable disorder of connective tissue occurs approximately once in 60,000 live births. Phenotypic characteristics include defective cranial ossification and severe skeletal deformity due to intrauterine rib and long bone fractures. Lethal OI may be associated with intracranial hemorrhage or severe respiratory insufficiency. Pulmonary hypoplasia has been previously observed in OI type II, but has not been defined clinically. The infant described herein was born with OI type II and pulmonary hypoplasia. Pathological examination of airway branching patterns indicated that lung development had progressed to only the 10 week stage with immature acinar development. Investigation type I collagen synthesis by cultured dermal fibroblasts revealed the presence of electrophoretically abnormal alpha 1(I) polypeptides. These findings suggest that biochemically regulated processes, as well as mechanical factors, may impeded pulmonary development in similar cases of OI type II.
A positive family history is considered a risk factor for osteoporosis (OP) although the genetic or biochemical basis for this relationship remains undefined. Various mutations affecting normal synthesis of type I collagen have been reported in osteogenesis imperfecta (OI), a heritable disorder of connective tissue. Family A, in which the proband and a daughter are afflicted with OP and idiopathic scoliosis was examined for defects in collagen metabolism. Dermal fibroblast cultures were established to investigate de novo collagen synthesis. SDS-PAGE revealed an abnormally migrating alpha 2(I) chain and procollagen in two generations. Examination of the kinetics of type I collagen pC & N-propeptide processing demonstrated a rate 2x control in the proband. The phenotype family A is not OI. It shares features with families B & C, having familial clustering of OP. However, collagen synthesis was not abnormal in family B & C. These data suggest that in family A the alpha 2(I) structural defect may be related to defective skeletal matrix formation.
It is controversial whether echocardiographic contrast agents prepared by sonication cause transient myocardial depression beyond that known to occur with contrast agents alone. In nine open chest dogs, contrast injections were made into the left anterior descending coronary artery during two-dimensional echocardiography. One hundred forty-four recordings were analyzed subsequently, by an observer who was unaware of other data, for percent depression of systolic wall thickening, duration of regional wall motion abnormalities, peak contrast enhancement and contrast washout. Two microbubble sizes were obtained by sonicating Renografin-76 (meglumine sodium diatrizoate): mean diameter 12 +/- 3 (SEE) and 20 +/- 6 micron. Four doses (range 0.5 to 3 ml) of each of four agents (12 and 20 micron bubbles in Renografin, nonsonicated Renografin and saline solution) were injected in random order. Significant relations were found between percent depression of systolic wall thickening, duration of regional wall motion abnormalities and contrast washout time versus microbubble size (p less than 0.001) and microbubble dose (p less than 0.01). Little increased contrast effect was found at larger doses or with larger microbubbles compared with the smaller doses and size studied. Injections of nonsonicated Renografin caused less depression of systolic wall thickening (p less than 0.05), faster resolution of wall motion abnormalities (p less than 0.05), less contrast (p less than 0.001) and more rapid contrast washout (p less than 0.001) than did 12 micron bubbles in Renografin. A significant correlation was found between the duration of regional wall motion abnormalities and contrast washout time (r = 0.93, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of dexamethasone on enkephalin-containing (EC) peptide levels and preproenkephalin mRNA levels was determined in adrenal medullary explants (glands) from sham and hypophysectomized (hypox) rats. Culture for 4 days in serum-free medium without dexamethasone resulted in a 13- and 4-fold increase in EC peptide levels in sham and hypox glands, respectively. The addition of dexamethasone (10(-5) M) produced a 20- to 26-fold increase in EC peptides in sham and hypox glands. In serum free medium, hypox glands showed a concentration dependent increase in EC peptides with the ED50 for dexamethasone equal to 5.7 x 10(-7) M. Since the glucocorticoid antagonist RU486 partially blocked the rise in EC peptides in sham glands, it appears that the increase in EC peptides in sham glands in the absence of dexamethasone is a result of a higher concentration of endogenous corticosterone in sham compared to hypox glands. Dexamethasone resulted in a 6-fold increase in preproenkephalin mRNA in hypox glands cultured for 2 days. This increase was approximately proportional to the increase in EC peptides seen at 4 days. In serum free medium progesterone, testosterone, and deoxycorticosterone failed to increase EC peptides in hypox glands. These results indicate that glucocorticoid treatment is required for maximal proenkephalin gene expression and EC peptide biosynthesis in cultured glands.
In vitro drug sensitivity assays have been developed with the goal of predicting the clinical response to chemotherapy. The colony-forming assay, radiolabeled precursor inhibition assay, and microcytotoxicity assay are most commonly used. In retrospective studies, the assays correctly predict clinical response to a chemotherapeutic agent in 50% to 70% of patients and predict clinical resistance in nearly 100% of patients. All of the assays suffer from technical and theoretical problems. In vitro assays depend on cell culture and therefore do not entirely simulate in vivo conditions. Heterogeneity in chemosensitivity is commonly found and can complicate the interpretation of results. Further investigation is needed to determine if these assays will be able to select prospective chemotherapy for patients. The malignant origin of the cells in culture must be verified if meaningful conclusions are to be made.
The 1978 Task Force Report on pediatric education encouraged increased participation by pediatricians in the health care of adolescents. A survey of pediatricians in the Los Angeles County area was conducted to assess the pediatrician's self-evaluation regarding the medical and psychosocial problems of the adolescent, the problems of the sexually active teenager, and the pelvic examination. A questionnaire was used to assess competence, level of comfort, ability to counsel, prior training, and the importance and relevance of these areas to pediatricians' practice. Areas of least and greatest competence were examined. Our results support the conclusion of the 1978 Task Force Report on pediatric education that there is inadequate training in adolescent health care issues. This appears to be especially true for issues relating to the sexually active teen and the pelvic examination.
While aortic root dilatation and valvular dysfunction have been well-documented in osteogenesis imperfecta (OI), the nature and extent of cardiovascular involvement in OI have not been clearly delineated. A clinical and echocardiographic survey involving 109 individuals with various nonlethal OI syndromes from 66 separate families was undertaken. Clinically discernible valvular dysfunction was encountered in only four of the 109 individuals (aortic regurgitation in two, aortic stenosis in one, and mitral valve prolapse in one), none of whom were related. Aortic root dilatation was recognized echocardiographically in eight (12.1%) of 66 individuals comprising a subset of the sample in which each family was represented by a single individual. The extent of the aortic root dilatation was mild (the largest dimension measuring 4.3 cm) and was unrelated to the age of the individual. Dilatation was seen in each of the different OI syndromes but was strikingly segregated within certain families (p less than .001). In the same subset of 66 individuals, mitral valve prolapse was encountered in two or 6.9% of the 29 individuals aged 15 years or greater in whom adequate studies were obtained. This observed frequency was not different from that seen in a normal adult population. Aortic root dilatation appears to represent a distinct phenotypic trait in patients with OI that is nonprogressive and occurs in about 12% of affected individuals. Whether mitral valve prolapse should be considered as a part of the cardiovascular phenotype in OI, or alternately segregates as an independent autosomal dominant trait has yet to be determined.
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Human malignant gliomas are karyotypically heterogeneous, composed of many cellular populations and isolated cell types identifiable by cytogenetic techniques. The distributions of cell types vary in high grade tumors. Some tumors are primarily near-diploid (35-57 chromosomes per cell), while others are hyperdiploid with chromosome numbers ranging from 58 to several hundred chromosomes per cell. Regional studies of several tumors suggest that the heterogeneity is not random. Anatomically different regions result from the combination of cellular distribution and their evolution over time. The karyotypic pattern of gliomas also reflects the tumor's evolution from a relatively homogeneous population of near-diploid cells to the hyperdiploid tumor that is removed by the neurosurgeon. The in vitro studies also suggest that there are phenotypic correlates to the karyotypic pattern of the tumor cells. Hyperdiploid cells are unstable in culture, tend to grow rapidly with short doubling times, and are often sensitive to such chemotherapeutic agents as BCNU. In contrast, the near-diploid cells are more normal in appearance, are stable in culture, grow slowly with long doubling times, are more likely to be resistant to the nitrosoureas and ultimately are the 'stem' cells that repopulate the tumor mass.