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Biomedical subjects

M Greenberg

Publications and source records attributed to M Greenberg.

At least 217 records · Page 12Linked to original sources

Sexually transmitted papillomaviral infections. I. The anatomic distribution and pathologic grade of neoplastic lesions associated with different viral types.

Multiple colposcopic biopsy specimens were collected from 160 women, with sampling of principal cervical and vulvar lesions as well as secondary areas of either minor acetowhitening or normal epithelium. Papillomaviral deoxyribonucleic acid was detected by Southern blot hybridization in 197 (90%) of the 218 principal biopsy specimens and 93 (46%) of 198 secondary biopsy specimens. Although different papillomaviruses were found at different sites in 31 women, only six of 416 specimens contained multiple types within the same sample. Specific viral types were associated with specific disease patterns. Only one of 80 type 6 or 11 infections had a diagnosis greater than cervical intraepithelial neoplasia, grade 2. In contrast, 42 of 48 (90%) biopsy specimens of cervical intraepithelial neoplasia, grade 3, or invasive cancer contained type 16, 18, or 31. Nonetheless, 12 of 124 (10%) cases of condyloma and cervical intraepithelial neoplasia, grade 1, were associated with types 16, 18, and 31 infections. Of 58 women with multicentric disease, 46 had positive hybridizations for both cervical and vulvar lesions (32 showing the same type in both samples and 14 showing different viruses). Differing patterns of papillomavirus-induced disease arise partly from the predilection of specific viral types for certain anatomic sites and partly through variations in host response. Detection of viral deoxyribonucleic acid in 46% of the secondary biopsy specimens suggests that disease expression may represent focal breakdown of host surveillance within a field of latent papillomaviral infection.

Biopsy↗

Use of SPECT to distinguish recurrent brain tumor from persistent activity at a craniotomy site.

A 50-year-old male underwent extensive left frontal lobe resection for a Grade II astrocytoma. Resection margins were free of tumor, and the patient suffered no significant postoperative neurologic deficits. One month later the patient was referred to radiation therapy for further evaluation and possible treatment. Unenhanced and enhanced transmission computed tomograms (CT) were interpreted as suspicious for recurrent tumor. However, using CT, which is essentially an anatomic technique, may not allow one to distinguish between surgical changes and the morbid anatomic findings of recurrent tumor. Because Tc-99m DTPA will cross the blood-brain barrier at sites of active intercranial disease, brain scintigraphy frequently is of value in distinguishing between recurrent tumor with an unstable blood-brain barrier and healed surgical changes with a stabilized blood-brain barrier. Therefore, clinicians requested that a Tc-99m DTPA brain scintigram be performed so as to distinguish between active disease and healed surgical changes.

Brain Neoplasms↗

Differential electrophysiologic properties of decremental retrograde pathways in long RP' tachycardia.

Long RP' supraventricular tachycardias (SVT) often demonstrate both slow and decremental conduction properties in the retrograde pathway of the reentrant circuit. The electrophysiologic properties of these pathways are poorly understood. We studied 10 patients with long RP' SVT (RP'/RR, 0.52 to 0.71); five had the unusual form of atrioventricular nodal reentry (fast-slow) and five patients had accessory AV pathways with slow, decremental retrograde conduction properties. During SVT, the effects of intravenous adenosine (37.5 to 150 micrograms/kg), which increases potassium current (iK) in supraventricular tissue and hyperpolarizes membrane potential toward Ek (-90 mV), and the response to slow-inward channel blockade with verapamil (0.10 to 0.20 mg/kg iv) were evaluated. Adenosine and verapamil has similar effects in the presence of fast-slow AV nodal reentry since both agents terminated SVT by producing block in the retrograde slow AV nodal pathway. In contrast, adenosine and verapamil had differential effects on retrograde conduction in decremental accessory pathways. Adenosine terminated all episodes of SVT in the retrograde decremental pathway, whereas verapamil had a direct effect on this tissue in only two of five patients. Decremental retrograde accessory pathways can therefore demonstrate at least two types of electrophysiologic responses. Pathways that respond only to adenosine-induced hyperpolarizing K+ current likely comprise depressed fast-Na+ channel tissue, i.e., partially depolarized (greater than -60 to -70 mV) atrial tissue. In contrast, decremental accessory pathways that respond to both modulation of the slow-inward calcium current and K+ conductance have pharmacologic properties similar to those of the AV node and may represent more completely depolarized atrial fibers with resting membrane potentials of -60 mV or less.

Adenosine↗

Suppression of anti-DNA antibody synthesis in vitro by a cross-reactive antiidiotypic antibody.

An understanding of the regulatory mechanisms that govern the humoral immune response will be facilitated by the availability of techniques for the measurement of specific antibody production in vitro. We have developed an enzyme-linked immunosorbent assay system for the measurement of in vitro anti-DNA antibody production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus. Using this technique, the PBMC from 74% of serologically active SLE patients produced levels of anti-DNA antibodies that were greater than 2 SD above the mean of 18 +/- 9 IU/ml for normal subjects. Furthermore, the addition of 3I, a monoclonal anti-idiotypic antibody that recognizes a cross-reactive determinant on anti-DNA antibodies, was shown to specifically inhibit anti-DNA production in vitro.

Antibodies, Anti-Idiotypic↗

Inhibition of cell growth mediated by plasmids encoding p53 anti-sense.

p53 is an oncogene product which has been shown to be directly involved in malignant transformation. Furthermore, it has been proposed that this protein plays an essential role in the control of cell proliferation. In the present study, we investigated the involvement of p53 in growth regulation of cells by employing anti-sense RNA methodology to inhibit p53 expression. Transfection with p53-specific constructs spanning the entire mRNA molecule or the 5' region of the gene led to reduced p53 protein synthesis. Clones derived from such transfected cells exhibited a slower rate of DNA synthesis, as assayed by incorporation of [3H]thymidine. In most cases, transfection of plasmids encoding anti-sense RNA eventually brought about the complete cessation of cell proliferation. No such effects were observed in L12 cells, which do not synthesize p53 and therefore do not depend on p53 expression for their growth, thus excluding the possibility of a non-specific toxic effect exerted by the anti-sense p53 RNA. These findings support the notion that p53 is essential for continuous cell proliferation.

Animals↗

Comminuted femoral shaft fractures.

Comminuted femoral shaft fractures are often grouped with more simple femoral fractures for study. Although union always occurs, shortening and angulation can result from closed treatment using traction and cast bracing. Operative intervention using locked intramedullary nails can lead to a consistently excellent outcome when the performance of the procedure is technically correct. The surgical procedure can eliminate a difficult management problem in multiply-injured patients.

Bone Nails↗

Quantitative analysis of cerebral asymmetries. Fronto-occipital correlation, sexual dimorphism and association with handedness.

To investigate the biological and functional significance of cerebral asymmetries, we measured lateral differences of the frontal and occipital poles on computed tomographic scans of 66 adult outpatients with no diagnosed abnormalities. In addition to confirming the greater average sizes of the right frontal and left occipital poles, we found a significant linear correlation relating anterior and posterior difference measures. Men showed greater degrees of frontal and occipital asymmetries than women; reversals of the typical asymmetries were more common among women. Reduction or reversal of the usual left occipital predominance in the presence of typical right frontal predominance was associated with non-right-handedness. These findings clarify and extend prior qualitative observations and relate to the possible role of testosterone in modulation of cortical asymmetries. Reduced structural asymmetries among women and non-right-handers may provide an anatomical basis for clinical and laboratory findings of lessened functional lateralization in these groups.

Adult↗

Is adenocarcinoma/large cell carcinoma the most radiocurable type of cancer of the lung?

Radiation therapy is widely considered the primary treatment for inoperable "non-small" cell carcinoma of the lung. In clinical investigations, distinction has been infrequent among the histopathologic subtypes of non-small cell carcinoma. Studies have shown significant differences between squamous cell carcinoma and adenocarcinoma/large cell carcinoma; adenocarcinoma/large cell carcinoma has a greater propensity for extrathoracic dissemination, especially to the brain, and it is less curable by resection when regional lymph node metastases are present. No differences have been documented between adenocarcinoma and large cell carcinoma. A retrospective study was undertaken to determine the results of definitive radiation therapy by histopathologic subtype of non-small cell carcinoma of the lung. Between July 1977 and April 1983, 134 patients with non-small cell carcinoma of the lung underwent definitive radiation therapy with curative intent. All patients had performance status scores of 80 to 100 (Karnofsky), and received minimum total doses within the tumor of 60 Gy in 6 to 7 weeks, five fractions per week. The median period of observation was 63 months. Ninety patients had squamous cell carcinoma; 44 had adenocarcinoma/large cell carcinoma. The two groups of patients were comparable in respect to age and Stage; there were significantly more women with adenocarcinoma/large cell carcinoma (27%) than with squamous cell carcinoma (13%). The median survival for patients with squamous cell carcinoma was 11.5 months; the 2 and 4 year survival rates were 21 and 7%, respectively. The median survival for patients with adenocarcinoma/large cell carcinoma was 18 months; 2 and 4 year survival rates were 38 and 23%, respectively. Comparison of the overall survival experience did not show a significant difference between the two cell types (p = .12 using Gehan's generalized Wilcoxon test). However, comparison of the proportion of patients with adenocarcinoma/large cell carcinoma surviving 18 months (50%) was significantly higher (p = .02) than that with squamous cell carcinoma (30%). A small body of data from the literature also suggests a better long-term prognosis for adenocarcinoma/large cell carcinoma. This observation requires confirmation from large trials with histopathologic review. If it is confirmed, there are important implications for therapeutic strategies in future clinical investigations of inoperable carcinoma of the lung.

Adenocarcinoma↗

Systemic and coronary effects of intravenous milrinone and dobutamine in congestive heart failure.

The effects of dobutamine and intravenous milrinone on systemic hemodynamics, coronary blood flow and myocardial metabolism were studied in 11 patients with severe congestive heart failure. Although milrinone and dobutamine similarly increased cardiac index from 1.9 +/- 0.4 to 2.5 +/- 0.4 liters/min per m2 (p less than 0.001) and from 1.9 +/- 0.4 to 2.8 +/- 0.8 liters/min per m2 (p less than 0.001), respectively, milrinone decreased left ventricular end-diastolic pressure to a greater extent than dobutamine, that is, from 26 +/- 6 to 12 +/- 8 mm Hg (p less than 0.001) versus 26 +/- 8 to 20 +/- 8 mm Hg (p less than 0.001). In contrast to dobutamine, milrinone significantly reduced mean systemic arterial and right atrial pressures. Dobutamine increased the first derivative of left ventricular pressure (dP/dt) from 1,013 +/- 309 to 1,360 +/- 538 mm Hg/s (p less than 0.01) but milrinone did not. Similarly, blood flow and myocardial oxygen consumption were increased by dobutamine from 152 +/- 87 to 187 +/- 118 ml/min (p less than 0.05) and from 17.7 +/- 10.9 to 21.5 +/- 14.9 ml O2/min (p less than 0.05), respectively, but were unchanged by milrinone. Both drugs significantly decreased coronary vascular resistance and myocardial oxygen extraction but did not change myocardial lactate extraction. Thus, dobutamine and milrinone produce similar improvement in cardiac index. However, dobutamine increases myocardial oxygen consumption, whereas milrinone does not. This difference can probably be explained by the substantial vasodilating properties of milrinone.

Aged↗

Pharmacokinetic determinants of 6-mercaptopurine myelotoxicity and therapeutic failure in children with acute lymphoblastic leukemia.

The pharmacokinetics of oral 6-mercaptopurine (6MP) was assessed in 20 children with acute lymphoblastic leukemia during maintenance therapy. The AUC was between 0 and 6 X 10 ng X min/ml, and AUC normalized to 1 mg/m2 of 6MP was between 0 and 815 ng X min/ml. Good correlation existed between peak concentrations and AUC (r = 0.866; P less than 0.001). In more than half of the cases there was evidence of prolonged elimination t1/2 or rebound of a serum concentration during the elimination phase corresponding to either an additional compartment or enterohepatic circulation of 6MP. One child did not achieve detectable concentrations on 2 different study days and was switched to a different protocol. The two children who had severe myelotoxicity achieved the largest AUC values per milligram per square meter of 6MP. Our results indicate that pharmacokinetic variability may contribute to either severe myelotoxicity or therapeutic failures. This suggests that monitoring of this drug in children with acute lymphoblastic leukemia may be helpful.

Administration, Oral↗

Extraadrenal pheochromocytoma: detection during pregnancy using MR imaging.

This case report demonstrates the usefulness of magnetic resonance (MR) imaging to demonstrate an abdominal mass during pregnancy. A pregnant woman presented in midgestation with symptoms and chemical evidence of a pheochromocytoma. The use of MR imaging permitted early localization of a retrouterine tumor when it would have been undesirable for the woman to undergo computed tomography because of radiation exposure. Evaluation of the MR images formed the basis of the therapeutic strategy used by the patient's physicians.

Adrenal Gland Neoplasms↗

The clinical application of an ELISA technique for the detection of antihistone antibodies.

A rapid reproducible technique for measuring antihistone antibodies is described in which unfractioned nuclear histones covalently bonded to plastic discs are employed in an ELISA system. All 20 patients with drug induced lupus erythematosus had antihistone antibodies, usually at high titer. In contrast, 22% of 18 asymptomatic patients with drug induced antinuclear antibodies (ANA), 15% of 20 patients with seropositive RA and 42% of 60 patients with systemic lupus erythematosus (SLE) had detectable antihistone antibodies. High titers of antihistone antibodies were not seen in drug induced ANA or RA. This assay differentiates between patients with drug induced lupus and drug induced ANA (p less than 0.01) and drug induced lupus erythematosus and SLE (p less than 0.01). In patients with SLE antihistone antibodies had no association with disease activity.

Antibodies, Antinuclear↗

Inescapable shock, neurotransmitters, and addiction to trauma: toward a psychobiology of post traumatic stress.

Chronic post traumatic stress has been described as a "physioneurosis" (Kardiner 1941), that is, a mental disorder with both psychological and physiological components. The behavioral sequelae of inescapable shock in animals and of massive psychic trauma in people show a striking parallel. Inescapable shock in animals leads to both transient catecholamine depletion and subsequent stress-induced analgesia. We postulate that the numbing and catatenoid reactions following trauma in humans correspond to the central nervous system (CNS) catecholamine depletion that follows inescapable shock in animals. We further explore the evidence for a human equivalent of "stress-induced analgesia" in animals, which is known to be mediated by endogenous opioids. Although reexposure to trauma may produce a paradoxical sense of calm and control due to endogenous opioid release, a cessation of traumtic stimulation will be followed by symptoms of opioid withdrawal and physiological hyperreactivity mediated by CNS noradrenergic hypersensitivity. This hyperreactivity can, in turn, be temporarily modified by reexposure to trauma. This factor could account for voluntary reexposure to trauma in many traumatized individuals and would provide a complementary formulation to the conventional psychodynamic concept of attempted mastery of the psychosocial meaning of the trauma.

Animals↗

Correlation of treatment volume with milligram-hours for intracavitary applications for carcinoma of the cervix.

Following the recommendations of the European Curietherapy Group, the three-dimensional dose distribution corresponding to various milligram-hour volumes has been analyzed according to its length, width, and height dimensions. Thus, it is possible to state the dimensions of a number of isodose surfaces for a dose prescription given in milligram-hours. Problems associated with the exact placement of the three-dimensional dose distribution in relation to the patient's anatomy are discussed.

Brachytherapy↗