Reliability of neurologic assessment in a collaborative study of HIV infection in children.
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Biomedical subjects
Publications and source records attributed to E Rodriguez.
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The i(12p) chromosome has been shown to characterize more than 80% of male germ cell tumors (GCTs) and is an important diagnostic marker. Although recent cytogenetic analyses of GCTs have defined nonrandom chromosome abnormalities in these tumors, no attempt has so far been made to compare i(12p)-positive and -negative tumors in terms of their cytogenetic, histologic, and clinical features. During a 5-year period, we have ascertained 202 GCTs, of which 117 had clonally abnormal karyotypes. Among the latter, 91 had one or more copies of i(12p), whereas 26 lacked an i(12p). We report here the karyotypic analysis of these 26 i(12p)-negative GCTs. In this group, nonrandom sites of chromosomal rearrangements included 12p13 (9/26) and 1p11-q11 (5/26). Comparison of the cytogenetic features of i(12p)-negative tumors with i(12p)-positive tumors revealed the only significant difference to be rearrangements affecting 12p13 in the former (35%) as compared to their absence in the latter (3%). Hybridization of metaphase preparations of 9 i(12p)-negative tumors with a chromosome 12 painting probe and with a microdissected 12p painting probe revealed extra copies of chromosome 12 segments incorporated into marker chromosomes whose composition could not otherwise be resolved by banding analysis; all were shown to be derived from 12p. These data demonstrate that both i(12p)-negative and -positive groups are characterized by an increased copy number of 12p, which is consistent with a lack of significant clinical or biological difference between them. An increased 12p copy number thus is a specific aberration of significance to the development of germ cell tumors.
This study examined the hypothesis that treatment with thyroxine (T4) would alter the coronary blood flow and signal transduction responses of the rabbit heart. T4 was administered for 16 days by subcutaneous time-release pellets (3 mg/kg/day) in 3 kg New Zealand white rabbits. Four groups of anesthetized open-chest rabbits (control, control+isoproterenol (ISO, 0.5 microgram/kg/min for 15 min), T4, and T4 + ISO) were used to determine coronary blood flow (radioactive microspheres), cyclic AMP content (competitive binding), low Km cyclic-AMP-phosphodiesterase activity (cyclic AMP-PDE, conversion of 3H-cyclic AMP to 3H-AMP) and beta-adrenoceptor number and affinity (125I-iodocyano-pindolol). Coronary blood flow was increased from control by ISO from 167 +/- 59 to 354 +/- 157 ml/min/100 g. T4 did not cause cardiac hypertrophy, but increased baseline coronary blood flow to 269 +/- 115 ml/min/100 g. The ISO response was attenuated in terms of blood flow (448 +/- 118) and heart rate with T4. Beta-adrenoceptor numbers increased significantly from 65.7 +/- 9.2 to 81.9 +/- 4.4 fmol/mg protein, while neither soluble (126 +/- 39 vs 119 +/- 15 pmol/mg protein/min) nor particulate cyclic AMP-PDE activity were different between control and T4 animals. Cyclic AMP content was increased from control by both ISO (779 +/- 239 to 1371 +/- 672 pmol/g) and T4 (1143 +/- 244). T4 animals showed a smaller increase in cyclic AMP following ISO (1391 +/- 261). There was not a significant difference between the control and T4 group cyclic AMP level following ISO. Thus, despite increased beta-adrenoceptor numbers, there was a diminished responsiveness of heart rate, coronary blood flow and cyclic AMP levels to isoproterenol in the T4-treated rabbit hearts.
We report the cytogenetic analysis of two cases of intra-abdominal desmoplastic small round-cell tumor, one of which had a t(11;22)(p13;q11.2) translocation. The same translocation has previously been reported in two other cases analyzed cytogenetically, indicating that it could be a consistent abnormality characteristic of this rare tumor entity.
Bioimpedance technology is being used increasingly to determine drug volume of distribution, body water status, and nutrition repletion. Its accuracy in patients experiencing large volume flux is not established. To address this, we undertook this prospective study in 54 consecutive seriously injured adults who had emergency celiotomy soon after arrival in the emergency department. Bioimpedance measurements were obtained in the emergency department before the patient was transported to the operating room, on completion of celiotomy, and 24 hours and 48 hours after celiotomy. Bioimpedance measurements of body water were compared with measured fluid balance. If insensible losses are subtracted from measured fluid balance, the percentage of body weight, which is body water determined by bioimpedance, closely follows fluid flux. This study supports the use of bioimpedance measurements in determining total body water even during periods of surgery, blood loss, and vigorous resuscitation.
1. This study tested the hypothesis that heterogeneity of myocardial adenylyl cyclase activity exists and contributes to the heterogeneity of blood flow in canine myocardium, in which flow varies in different areas at any one moment or in a single area at different times. 2. Tissue adenylyl cyclase activity was measured simultaneously with coronary blood flow in the left ventricle of eight anaesthetized open-chest dogs. Coronary flow was measured using radioactive microspheres under control conditions and after sympathetic stimulation. The ventricle was cut into 15 subepicardial and 15 subendocardial sections in which both flow and adenylyl cyclase (basal and forskolin-stimulated) activity were assayed. 3. Control coronary flow was 73.1 +/- 19.9 ml min-1 100 g-1 and ansa subclavia nerve stimulation increased flow to 93.2 +/- 26.1. Baseline adenylyl cyclase activity averaged 51.9 +/- 38.8 pmol min-1 mg protein-1, while forskolin-stimulated activity was 588.2 +/- 393.6. Method variability was approximately 10% of the mean, much less than the biological variability of 70%. 4. Regression analysis of control flow vs baseline adenylyl cyclase activity produced the equation: flow = 0.25 (Adenylyl Cyclase)+60.6, (r = 0.47, P < 0.0001). The equation for stimulated flow vs stimulated adenylyl cyclase was: flow = 0.03 (Adenylyl Cyclase)+73.1, (r = 0.51, P < 0.0001). 5. Thus, significant heterogeneity of tissue adenylyl cyclase activity existed in the heart. There was also a direct linear relationship between adenylyl cyclase activity and coronary flow heterogeneity in canine left ventricle.
Several acetogenins, characteristic of the Annonaceae, have been found to exhibit pesticidal and feeding-deterrent activities against a variety of pests and are undergoing commercial development as pesticides. The sensitizing potential of one of these plants, pawpaw, Asimina triloba Dunal, was examined in the current study. The potential of Fraction F020 (a pesticidal crude extract of pawpaw stem bark) to sensitize and elicit an allergic contact dermatitis response was determined by using a modified guinea pig maximization test (GPMT). Fraction F020 is a weak sensitizer and the active compound, asimicin, a trihydroxy-bistetrahydrofuran fatty acid gamma-lactone, is a weak irritant.
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Serum levels of tumor necrosis factor alpha/cachectin (TNF alpha) were studied in a group of adult patients with sickle cell disease (SCD), which include 31 patients with homozygous SS hemoglobinopathy and 10 patients bearing double heterozygous SC hemoglobinopathy and in their matched normal controls. All patients tested did not show any form of crisis for at least 4 weeks prior to the extraction of the sample. The amount of TNF alpha in serum was quantitated by means of an immunoenzymatic assay with a lower limit of detection of 25 pg/ml. The percentage of sera with detectable levels of TNF alpha was significantly increased in SCD patients as compared with the normal controls. Mean TNF alpha values in individuals with detectable levels of the cytokine were also significantly higher in the whole group of SCD patients and in patients bearing either SS or SC hemoglobinopathies than in the control group. An inverse correlation was observed between the percentages of Hb F and the levels of TNF alpha found in the sera from the patients.
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The objective of this article is to consider whether randomized clinical trials (RCTs) are able to determine the validity of transferring treatments for major depression from the psychiatric to the primary care sector. This clinical issue is of growing concern in the United States since both governmental and professional bodies are establishing guidelines for the treatment of medical patients with the affective disorder. The article's method involves analysis of how the competing aims of rigorous scientific methodology (internal validity) and generalization of study findings (external validity) are best balanced within the RCT. Experiences in recruiting medical patients with major depression and providing pharmacologic, psychotherapeutic, and usual care interventions compatible with the sociotechnical characteristics of ambulatory medical centers are described to illustrate the complexities of investigating transferability of treatments for major depression with RCT methodology.
Numerical changes affecting chromosomes 1, 2, 3, 4, 6, 7, 8, 10, 11, 12, 16, 17, 18, and the X and Y chromosomes have been analyzed using chromosome-specific centromeric alpha-satellite repeat DNA probes in a panel of biopsies of six gastric and three esophageal adenocarcinoma and one epidermoid carcinoma of esophagus obtained at surgery. For each case, with each probe, the number of hybridization signals were determined in 200 nuclei. Hybridization of each probe to phytohemagglutinin-stimulated normal peripheral blood lymphocytes served as controls. Monosomy was defined by loss of one signal in 15% or more cells and trisomy or tetrasomy was defined by the presence of 3 or 4 signals in 7% or more cells, respectively. The Y chromosome was lost in 6 of 8 cases and monosomy 10 was seen in 5 of 10 cases. Trisomy for chromosomes 17, 8, 7, 12, 11, and 1 was seen in 4 of 10, 4 of 10, 4 of 10, 2 of 10, 2 of 8, and 2 of 10 cases, respectively, and tetrasomy for chromosome 7 was seen in 1 of 10 cases. These data show that the Y chromosome and chromosomes 10, 8, 7, 17, and 12 are most frequently involved in nondisjunctional changes in these tumors. They also document the feasibility and utility of interphase cytogenetics of gastric adenocarcinomas.
The major structural and functional determinants of impaired left ventricular diastolic function in the hypertensive patient are reviewed, together with the indices normally used to detect this failure. The alteration of functional determinants can be quickly modified, while structural determinants are modified only over the long term. Drug therapy first affects the functional determinants, bringing about their attenuation and initiating the modification of the structural factors, thus accounting for the improvement in diastolic function over the long term.
Stress thallium scintigraphies are frequently positive in patients with systemic hypertension (SHT), especially in the presence of left ventricular hypertrophy (LVH). In order to determine whether positive thallium perfusion scans in patients with LVH secondary to SHT and normal coronary angiographies are due to segmentary reduction of coronary reserve (CR), we have studied 10 out of 60 consecutive cases of SHT with echocardiographic LVH, using intracoronary Doppler. We compared coronary blood flow velocity at rest and post-papaverine (PP), and CR in at least two major coronary vessels, always including the one corresponding to the ischaemic segment. In the vessel with the least CR at rest, a new determination of CR was made under intracoronary nitroglycerin. A group of five normal patients acted as controls. The mean CR of the controls and patients, respectively, was 6.2 +/- 1.4 vs 2.7 +/- 0.9 (P < 0.001). In patients with positive thallium perfusion scans, the coronary arteries corresponding to the ischaemic segments had less CR (2.5 +/- 0.6) than arteries from non-ischaemic segments (3.4 +/- 1, P < 0.05). These differences were greater when the ischaemia was anterior. There was no correlation either between CR and left ventricular mass (r = 0.23) or rest coronary blood flow velocity (r = 0.07). Only one patient exhibited functional behaviour indicating reduced CR; this rose from 1.9 to 7.5 after nitroglycerin 300 micrograms. In conclusion, CR determined by intracoronary Doppler and papaverine shows segmentary differences both in normal patients and in patients with LVH and normal coronary angiograms. This could be the cause of segmental ischaemia detected by means of radionuclide stress tests.
A clinical pathophysiological classification of hypertensive cardiomyopathy has been established on the basis of the degree to which the heart is affected by chronic, systemic arterial hypertension: Degree I: Asymptomatic patients without left ventricular hypertrophy but with left ventricular diastolic dysfunction according to Doppler mitral inversion relation (E/A < 0.9) or to gamma scintigraphy (peak filling rate reduction < or = 2.7 EDC.s-1. These patients are classified as Group 1. Degree II: Asymptomatic or mildly symptomatic patients (New York Heart Association class I) with echocardiographic left ventricular hypertrophy; classified as Group IIA or IIB according to whether weight-adjusted maximal oxygen uptake is normal or below normal, respectively. Degree III: The basic characteristic is the presence of congestive heart failure with normal ejection fraction (EF > or = 50%). Two subsets can be distinguished on the basis of degree of hypertrophy: Group IIIA, with a mass/volume index > 1.8, and IIIB with a mass/volume index < 1.8. The differences between the two are as follows: patients classified as IIIA had a lower rate of regional ischaemia, a higher ejection fraction, a more frequently audible fourth sound, rarely a third sound and a cardiothoracic ratio < 0.5; IIIB patients had a higher prevalence of regional ischaemia (thallium-positive), a frequently audible third sound and a cardiothoracic ratio > 0.5. Degree IV: This category is characterized by the presence of depressed contractility, which could cause heart failure, by an ejection fraction < 50% and an increase in ventricular volumes. Echocardiography shows increased distance between mitral point E and the septum.
Although the biologic significance of germ-cell tumors to the study of malignancy and differentiation has been well recognized for some time, detailed genetic analysis based on fresh tumor biopsies has not been initiated until recently. The first stage of such studies, as with other, more extensively investigated, tumor systems, has been cytogenetic analysis. To date, cytogenetic data on close to 200 tumors are available, which have already yielded valuable insights into the biology of these tumors, as well as a clinically useful marker. Thus, initial correlations between chromosome change and histologic type have been recorded, gene amplification associated with malignant progression has been identified, the cytogenetic basis of malignant differentiation in teratomatous lesions has been clarified, and sites of candidate tumor suppressor genes unique to this system have been identified. The usefulness of i(12p) as a diagnostic marker, especially in tumors of uncertain histologic type, has been established. Because of the clinical usefulness of this marker, molecularly based methods for its detection, without the need for formal cytogenetic analysis, have been developed. Cytogenetic analysis of larger prospectively ascertained series than have been studied so far and analysis of large numbers of tumors utilizing molecular techniques can be expected to yield significant insights into the biology and clinical behavior of these tumors.
The identification of nonrandom chromosomal abnormalities in hematologic and solid tumor malignancies, which can serve as specific diagnostic markers, has permitted the application of cytogenetic techniques to the diagnosis of poorly differentiated carcinomas of unknown primary tumor site. Cytogenetic markers specific for germ cell tumors, neuroepithelial tumors, and lymphoma have now been identified in these patients. In the case of germ cell tumor diagnosis, the finding of a cytogenetic marker specific for germ cell cancer was predictive of responsiveness to cisplatin-based chemotherapy and long-term disease-free survival. DNA hybridization techniques, including quantitative Southern blot analysis and FISH, were also used to establish the diagnosis of germ cell tumor, particularly in the setting in which conventional cytogenetic analysis was unsuccessful. In poorly differentiated tumors in which conventional light microscopic, immunohistochemical, and electron microscopic techniques fail to yield a specific diagnosis, the use of molecular and cytogenetic markers in human malignancy promises to increase diagnostic acuity. These techniques have the potential to give clearer insight into the biology of this heterogeneous group of tumors and assist in directing appropriate therapy to patients who indeed may have a highly treatable disease.