Biomedical subjects
M Marcus
Publications and source records attributed to M Marcus.
Adolescence and pregnancy outcome.
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Identification of a novel transcription factor, ACF, in cultured avian fibroblast cells that interacts with a Marek's disease virus late gene promoter.
Interactions between factors in duck and chick embryo fibroblast (DEF and CEF, respectively) nuclear extracts and the Marek's disease virus (MDV) gp57-65 gene promoter were investigated. Results of in vitro transcription and gel mobility-shift assays indicated that multiple cellular factors interact with 5'-flanking sequences of the MDV gp57-65 gene. One sequence-specific DNA binding activity (termed ACF for avian cell factor(s)) was identified by interaction of DEF and CEF nuclear extract proteins with a particular site (nucleotides -193 to -177) in the MDV gp57-65 gene promoter. Binding of ACF to its apparent recognition sequence, contained within the 17-bp oligonucleotide 5'-CTAGTTTACTTGTTTGT-3' (ACF-12), was highly sequence-specific. Radiolabeled ACF-12 oligonucleotide bound significant ACF protein in the presence of a 400-fold molar excess of unlabeled nonspecific competitor DNA. A similar amount of specific competitor completely abolished ACF binding to probe DNA. Deletion of the ACF binding site from MDV gp57-65 gene promoters linked to a chloramphenicol acetyltransferase (CAT) reporter gene reduced expression of CAT activity by twofold relative to that seen with a gp57-65 promoter-CAT construct containing an intact ACF binding site. Transfection inhibition assays using double-stranded ACF binding site competitors reduced steady-state levels of gp57-65 mRNA in MDV infected cells by over twofold relative to those in control infected cells. Introduction of a similar amount of nonspecific double-stranded oligonucleotide had no adverse effect on gp57-65 mRNA levels. These data suggest that ACF is important for efficient expression of gp57-65.
High-energy shock waves: in vitro effects.
To date, there have been multiple studies on the effects of high-energy shock waves (HESW) on benign and malignant cells under in vitro conditions. The major problem in comparing and contrasting these studies has been the wide range of mechanical, biological, and analytical variables facing the investigator. However, if one takes the time to select out only those studies in which a wide range of experimental variables have been defined or controlled, then it becomes possible to begin to understand the effects of HESW on cells in vitro. With this in mind, the literature has been thoroughly reviewed. It would appear that HESW do cause cellular damage regardless of the cell's doubling time. The cell damage is likely due to the impact of cavitation and the attendant shear forces and jets that are produced by the shock waves as it passes through the cell suspension. The damage occurs both at the cell membrane and within the cell itself. With regard to the latter, it would appear that the mitochondria are most sensitive to HESW; however, damage also occurs within the nucleus and along the endoplasmic reticulum and in other cell organelles (eg, lyosomes). Applications of HESW to other clinical situations are currently being studied. One example of interest is the in vitro combination of chemotherapeutic agents and HESW to enhance the effect of a specific chemotherapeutic regimen on a given tumor cell line. Several investigators have noted a beneficial effect of this combination therapy in vitro; however, similar favorable results have not been obtained when the same or similar tumor system was studied in vivo.
Visual parameters in patients with pituitary adenoma before and after transsphenoidal surgery.
Eighty-two patients with pituitary adenoma who underwent transsphenoidal surgery were examined before and after surgery. Nineteen patients had a normal preoperative neuro-ophthalmological examination. All of these patients maintained normal visual parameters postoperatively. The remaining 63 patients had tumour-related loss of visual acuity, visual field, or both. These patients ranged in age from 18 to 78 years. Duration of symptoms ranged from one day to ten years, with a median of six months. Preoperative visual acuity was 6/12 or better in 72% of eyes, with 90% of patients having 6/12 or better in their better eye. Only 7% of eyes had a normal preoperative visual field. Both visual acuity and visual field improved postoperatively in the majority of eyes. In eyes that were examined within one week after surgery and subsequently, substantial improvement occurred within the first postoperative week, but further improvement continued over weeks to months postoperatively, with visual field taking longer to stabilise than visual acuity. Visual acuity at last examination was 6/12 or better in 87% of eyes, and visual field at last examination was normal in 50% of eyes. A total of 92% of patients had visual acuity of 6/12 or better in their better eye, and 62% of patients had a normal visual field in their better eye. Visual acuity at last examination was correlated with both age and preoperative visual acuity. Last visual field also was correlated with both age and preoperative visual field. Patients with preoperative optic atrophy had a poorer visual prognosis than did patients with normal fundi.
Regional three-dimensional geometry and function of left ventricles with fibrous aneurysms. A cine-computed tomography study.
BACKGROUND: To assess the extent and nature of the dysfunction surrounding aneurysms of the left ventricle (LV), we examined the parameters of local and global three-dimensional shape, size, and function of LVs of eight patients with histologically confirmed anterior fibrous aneurysms. METHODS AND RESULTS: Three-dimensional reconstructions of each LV were made from 10-12 short-axis fast cine-angiographic computed tomography (cine-CT) slices encompassing the entire heart at end diastole and end systole. Regional three-dimensional wall thickness, thickening, motion, curvature, and stress index were calculated for 84 elements encompassing the entire LV. The aneurysmal border was defined by a sharp decrease in end-diastolic wall thickness and separated the LV into an aneurysmal zone and a normal zone that was further divided into adjacent normal (AN) and remote normal (RN) zones. As expected, thickening was negligible in both the aneurysmal and the border zones. Although both the AN and the RN zones had normal wall thickness (1.05 +/- 0.20 and 1.09 +/- 0.20 cm, respectively), thickening was depressed in the AN (0.22 +/- 0.08 cm) but not the RN (0.44 +/- 0.19 cm) zones. The size of the dysfunction zone (defined as less than 2 mm thickening) was found to be considerably greater than the anatomic size of the aneurysm (60.9 +/- 13.7% versus 33.6 +/- 7.6% of the left ventricular endocardial area, respectively; p less than 0.001). In addition, the AN zone had a smaller curvature and a higher stress index than the RN zone. CONCLUSIONS: LVs with fibrous aneurysms are characterized by a relatively large region of nonfunction that encompasses the thin aneurysmal area and its transitional border zone, a normally functioning remote zone, and an intermediate region of normal wall thickness but with reduced function, which may be attributed to its low curvature and high stress index.
Graves' orbitopathy and restrictive myopathy.
Restrictive myopathy in Graves' orbitopathy is a disabling disorder, difficult to treat, involving clinically the inferior and medial recti. Most patients do not return to the normal, premorbid state of muscular alignment and the goal of treatment is to reach binocular vision in the important directions of gaze--straight ahead (primary position) and downgaze (reading position). The treatment in the acute, congestive stage is optical, prisms or patching, or medical. The medical treatment principally consists of a course of oral or intravenous corticosteroid treatment, and in selected patients orbital irradiation can be of benefit. Surgery is performed on the euthyroid patient after the muscular imbalance has stabilized, usually six months from the onset of the disorder. The mainstay of therapy is a large recession of the involved muscles, if possible on an adjustable suture. Sometimes marginal myotomies are added to the muscle recession. A fadenoperation on the contralateral, minimally involved inferior rectus has been suggested as a means of increasing muscular alignment in both primary position and downgaze. Thorough evaluation of the course of the disease, and the benefit of different treatment modalities is possible only with long term follow-up.
Idiopathic intracranial hypertension.
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Relative accuracy of three scintigraphic methods for determination of right ventricular ejection fraction: a correlative study with ultrafast computed tomography.
The accuracy of three scintigraphic methods for determination of right ventricular ejection fraction (RVEF) was tested in 29 patients using ultrafast computed tomography (UFCT) as the gold standard. RVEF measurements by the ECG-gated first-pass approach showed excellent correlation with the UFCT results (r = 0.96, y = 0.06 + 0.91x), while both the standard gated acquisition blood-pool imaging (r = 0.71, y = 0.14 + 0.59x) and the nongated first-pass curve approach (r = 0.63, y = 0.18 + 0.37x) significantly underestimated RVEF. The error can be ascribed to partial inclusion of the atrial activity in the region assigned to the right ventricle. The tricuspid valve plane was found to move by a distance equal to 9%-33% (mean = 20%) of the right ventricular long-axis between systole and diastole. This translational motion was more pronounced with higher EFs.
Epidemiologic studies of VDT use and pregnancy outcome.
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A proposed new system for valuing dental procedures. The relative time-cost unit.
The relative time cost unit (RTCU) is a proposed new system for valuing dental procedures that provides an alternative to traditional relative value units in fee-setting and reimbursement allowances. It incorporates personnel costs, task mixes, and task times into relative weights for dental procedures. The frequently performed procedure, "2-surface amalgam restoration," is used to illustrate how the RTCU values are derived from hospital task analysis data. The RTCU, as a data-based construct, holds appeal for restructuring fee schedules and has been used for almost a decade by insurance companies to value dental services, construct fee schedules, and evaluate reimbursement to providers.
Comparison of two-dimensional echocardiography and ultrafast cardiac computed tomography for evaluating intracardiac thrombi in cerebral ischemia.
Two-dimensional echocardiography has a high specificity for the detection of intracardiac thrombi, but technically difficult studies are often encountered. Ultrafast cardiac computed tomography may be useful in such cases. Using transthoracic two-dimensional echocardiography and ultrafast cardiac computed tomography, we studied 36 patients with cerebral ischemia; one patient had the studies performed on two occasions, making a total of 37 sets of studies. Technical difficulties occurred in 12 echocardiographic (32%) and two ultrafast cardiac computed tomographic (5%) studies. The two techniques agreed in 29 sets of studies (78%). Among the eight discrepant sets of studies, two-dimensional echocardiography was positive for a left ventricular thrombus while ultrafast cardiac computed tomography was negative in three and equivocal in one and echocardiography was equivocal while ultrafast cardiac computed tomography was negative in two and positive in one. In the latter case, a left ventricular thrombus was confirmed at autopsy. In the other discrepant set of studies echocardiography was negative while ultrafast cardiac computed tomography revealed a left atrial and appendage thrombus. Because of its ease of performance and safety, two-dimensional echocardiography is the appropriate initial screening test for left ventricular thrombus. Ultrafast cardiac computed tomography can provide additional information in patients with technically difficult or equivocal two-dimensional echocardiographic studies or patients with cardiac disorders predisposing to atrial thrombi formation.
Detection of adducts of deoxyribonucleic acid in white blood cells of roofers by 32P-postlabeling. Relationship of adduct levels to measures of exposure to polycyclic aromatic hydrocarbons.
To assess the utility of adducts of deoxyribonucleic acid (DNA) as biomarkers of exposure to carcinogens in an industrial population, a pilot study of roofers occupationally exposed to polycyclic aromatic hydrocarbons was conducted. DNA isolated from white blood cells of roofers and nonoccupationally exposed comparison subjects matched for age, sex, and smoking status was analyzed for DNA adducts with the use of 32P-postlabeling methods. Occupational exposures to polycyclic aromatic hydrocarbons were assessed by personal air sampling and skin wipes. Ten of the 12 roofers, but only 2 of the 12 comparison subjects, had detectable levels of aromatic DNA adducts in the 32P-postlabeling assay. Among the roofers, the post-shift levels of polycyclic aromatic hydrocarbons in the skin wipes were correlated with the DNA adduct levels. These results suggest that 32P-postlabeling assay may be useful for monitoring internal exposures to complex mixtures of aromatic hydrocarbons in industrial populations.
A pilot study of detection of DNA adducts in white blood cells of roofers by 32P-postlabelling.
To assess the utility of DNA adducts as biomarkers of exposure to carcinogens in an industrial population, a pilot study of roofers occupationally exposed to a mixture of polycyclic aromatic hydrocarbons was conducted. DNA was isolated from peripheral white blood cells of roofers and non-occupationally exposed subjects matched for age, sex and smoking status. Occupational exposures to anthracene, fluoranthene, pyrene, benzanthracene, benzo[a]pyrene, benzo[b]fluoranthene, benzo[g,h,i]perylene and benzo[k]fluoranthene were assessed by personal breathing zone air sampling and skin wipes. Exposures to benzo[a]pyrene in air of exposed subjects ranged from 0.60 microgram/m3 to 1.39 micrograms/m3, and exposures to total polycyclic aromatic hydrocarbon (the sum of eight hydrocarbons) ranged from 6.0 micrograms/m3 to 13.8 micrograms/m3 on the day before blood collection. In the biomarker studies 10 of 12 roofers, but only 2 of 12 comparison subjects, had detectable levels of aromatic DNA adducts by 32P-postlabelling assay (p less than 0.01). The two non-roofers with detectable adducts had levels at or near the detection limit of 2 adducts per 10(9) nucleotides. In two roofer samples which were studied in a mixing experiment, the major adduct spots did not co-migrate with the guanosine N2 adduct of benzo[a]pyrene diol epoxide. These results suggest that the 32P-postlabelling assay may be useful for monitoring exposures to complex mixtures of aromatic hydrocarbons in industrial populations.
Trends in quality assurance in the dental profession.
I have dealt with three questions concerning trends in quality assurance. In summary, we must ask ourselves whether the profession can develop methods for dealing effectively with dentists whose performance is found to be continually unsatisfactory. This may be achieved by making available effective tools for others to use in developing quality assurance systems. These tools will involve criteria and standards for services, appropriateness of treatment, measuring outcomes of care, and methods for assessing dental practices. This may involve working closely with consumer representatives to assist in gaining the consumer's point of view and incorporating it into the technology of quality assurance. Berwick, in a recent article in the New England Journal of Medicine, called for the application of a "Theory of Continuous Improvement" rather than the "Theory of Bad Apples." His view is that we should examine the process itself and try to improve it rather than look for outliers or bad apples. His point of view is consistent with the concept of quality assurance I have been talking about. Quality assurance systems should assure quality by proper assessment, identifying strengths and weaknesses in the provision of care. The strengths should be reinforced and the weaknesses should be rectified. This necessitates positive communication between those who perform quality assurance and those who are being evaluated. It also assumes that the technology is appropriate, recommendations are reasonable and that, when changes are made, quality will improve. In order to make the theory of continuous improvement work, it should be consistent with financial incentives and professional values.(ABSTRACT TRUNCATED AT 250 WORDS)
Assessment of probability of survival in penetrating injuries using the TRISS methodology.
By the TRISS methodology, probability of survival in injury can be estimated. It is based on a statistical analysis of outcome which is influenced by the severity of the injuries as expressed in the Injury Severity Score (ISS), the physiological function as expressed in the Trauma Score (TS) and the patient's age. We have used the TRISS formula in 206 patients with penetrating injury. Of these patients, 149 sustained stab wounds, 32 gunshot wounds and 25 others. ISS ranged from 2 to 38, the mean ISS being 9. The function was good (TS greater than 14) in 85 per cent. Estimated probability of survival ranged from 1.00 to 0.42. Three patients (1.5 per cent) died. The probability of their survival was 0.92, 0.96 and 0.98, respectively. All the fatal cases had serious predisposing conditions: chronic pulmonary disease, alcoholism, and psychiatric illness. In penetrating injury, the patient's functional status at the start of treatment is of greater importance for the outcome than the anatomical severity. The concept of the methodology of TRISS for assessment of probability of survival seems useful for review and comparison in injury care.
5-aza-C-induced changes in the time of replication of the X chromosomes of Microtus agrestis are followed by non-random reversion to a late pattern of replication.
Treatment with 5-azacytidine (5-aza-C) causes an advance in the time of replication and enhances the DNase-I sensitivity of the inactive X chromosome in Gerbillus gerbilllus fibroblasts. We found that these changes were not stably inherited and upon removal of the drug the cells reverted to the original state of one active and one inactive X chromosome. In order to determine whether this reversion was random, we used a cell line of female Microtus agrestis fibroblasts in which the two X chromosomes are morphologically distinguishable. In this work we show that the reversion to a late pattern of replication is not random, and the originally late replicating X chromosome is preferentially "reinactivated", suggesting an imprinting-like marking of one or both X chromosomes. The changes in the replication pattern of the X chromosome were associated with changes in total DNA methylation. Double treatment of cells with 5-aza-C did not alter this pattern of euchromatin activation and reinactivation. A dramatic advance in the time of replication of the entire X linked constitutive heterochromatin (XCH) region was however, observed in the doubly treated cells. This change in the replication timing of the XCH occurred in both X chromosomes and was independent of the changes observed in the euchromatic region. These observations suggest the existence of at least two independent regulatory sites which control the timing of replication of two large chromosomal regions.
Ascorbic acid and vitamin B12.
Using extraction procedures in which the extracted vitamin B12 was protected by cyanide or metabisulfite, several investigators found no change in vitamin B12 when meals were incubated in the presence of ascorbic acid for 30 minutes at 37 degrees C. A previous report suggested degradation of vitamin B12 under these conditions, but this was apparently caused by incomplete protection of the extracted vitamin B12 in the assay procedure. If incubation at 37 degrees C for 30 minutes is a laboratory mimic of the gastric environment, one must conclude that high doses of ascorbic acid do not affect the stability of vitamin B12 in vivo.