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Biomedical subjects

S Goldman

Publications and source records attributed to S Goldman.

At least 181 records · Page 10Linked to original sources

Association of serum immunoglobulin G antibodies against human papillomavirus type 16 capsids with anal epidermoid carcinoma.

BACKGROUND: Anal epidermoid carcinoma is a relatively rare tumor, but its incidence has been increasing rapidly during the past few years. Genetic material from the major oncogenic types of human papillomavirus (HPV), types 16 and 18, has regularly been demonstrated in a substantial proportion of anal cancers, suggesting an etiologic role of HPV infection. Recently, serum antibodies against HPV type 16 capsids were shown to be a serologic measure of HPV16 infection. PURPOSE: We investigated whether serum antibodies against HPV16 capsids are associated with an increased risk of developing anal cancer. METHODS: Serum samples from 64 patients (48 women and 16 men) with untreated anal epidermoid cancer and from 79 age- and sex-matched healthy blood donors were analyzed for the levels of serum immunoglobulin G (IgG) against capsids of HPV16 by the enzyme-linked immunosorbent assay. The levels of serum IgG against HPV type 6 and bovine papillomavirus (BPV) capsids, as well as against HPV16 peptide antigens, were also measured. RESULTS: Whereas antibodies against HPV6 or BPV capsids were not significantly associated with anal cancer, the presence of IgG against HPV16 capsids exceeding the anti-BPV antibody levels was demonstrated among 55% (35 of 64) of the case patients but only among 4% (three of 79) of the control subjects (odds ratio [OR] = 30.4; 95% confidence interval [CI] = 8.4-161.5). Antibodies against HPV16 E2 and E7 peptides were also more common among case patients (OR = 12.8 and 95% CI = 5.4-31.5 for E2; OR = 3.0 and 95% CI = 1.4-6.7 for E7). CONCLUSION: The results suggest that HPV16 capsid antibodies are serologic markers for anal cancer. IMPLICATION: Exposure to HPV16 or related viruses appears to be a major risk factor in the majority of anal cancers.

Aged↗

Brain hypometabolism of glucose in anorexia nervosa: a PET scan study.

Cerebral glucose metabolism was studied in 20 underweight anorectic girls and in 10 age- and sex-matched healthy volunteers using positron emission tomography with (18-F)-fluorodeoxy-glucose. Both groups were scanned during rest, with eye closed and with low ambient noise. Compared to controls, the underweight anorectic group showed a global hypometabolism (p = .002) and an absolute (p < .001) as well as relative (p < .01) hypometabolism of glucose in cortical regions, with the most significant differences found in the frontal and the parietal cortices. Within the underweight anorectic and the control groups, no correlations were found between absolute or relative rCMRGlu and BMI, anxiety scores, or Hamilton scores of depression. Different factors might explain this reduction of glucose metabolism in anorexia nervosa. It might be the consequence of neurophysiological or morphological aspects of anorexia nervosa and/or the result of some associated symptoms such as anxiety or depressed feelings. Supported by cognitive studies, we can also hypothesize a primary corticocerebral dysfunctioning in anorexia nervosa.

Adolescent↗

Left ventricular performance and remodeling in rabbits after myocardial infarction. Effects of a thyroid hormone analogue.

BACKGROUND: Because the rat postinfarction model differs from human heart failure with respect to the composition of myosin heavy chain (MHC) isoforms and other contractile proteins, alternative animal models are needed for the development of new treatments for human heart failure. The purpose of this study was threefold: (1) to test the feasibility of using the V3(beta,beta) rabbit postinfarction model for the study of heart failure by characterizing the effects of chronic coronary artery occlusion on the left ventricle; (2) to determine whether the thyroid hormone analogue 3,5-diiodothyropropionic acid (DITPA) produces improvements in left ventricular function; and (3) to determine the effects of myocardial infarction and treatment with DITPA on MHC protein isoforms. METHODS AND RESULTS: Male New Zealand White rabbits underwent proximal circumflex coronary artery ligation. After infarction, rabbits were treated with DITPA (3.75 mg/kg body wt) or placebo for 21 days and then underwent conscious and open-chest hemodynamic studies. In separate groups of rabbits, beta- and alpha-MHC isoforms were separated, and relative proportions were measured using gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis and laser densitometry. Infarction resulted in increased left ventricular end-diastolic pressure and prolonged left ventricular relaxation (tau) (P = .001 for both variables). Postinfarction treatment with DITPA decreased left ventricular end-diastolic pressure and tau (P = .002 and P = .001, respectively) and increased maximum positive and negative dP/dt (P = .002 and P = .016, respectively). Infarcted rabbits treated with DITPA had no significant changes in heart rate or left ventricular systolic pressure compared with untreated rabbits with infarction. There were no significant differences in heart rate, positive dP/dt, peak systolic pressure, or tau between sham-operated rabbits and sham-operated rabbits treated with DITPA. Although infarction resulted in increased left ventricular diameter, there were no effects of DITPA on left ventricular remodeling. Neither myocardial infarction nor treatment with DITPA altered the ratio of MHC isoforms. CONCLUSIONS: Rabbits that survive occlusion of the circumflex artery will develop myocardial dysfunction and left ventricular remodeling. Therapy with DITPA, a thyroid hormone analogue, produces improvement in ventricular performance and reduces end-diastolic pressure. The hemodynamic effects of DITPA were not associated with alterations of MHC isoforms. Whether DITPA represents the prototype of a previously undescribed class of agents for the treatment of heart failure will need to be determined by clinical trials.

Animals↗

Effect of pergolide on endogenous and exogenous L-DOPA metabolism in the rat striatum: a microdialysis study.

We used a model of intrastriatal microdialysis in freely moving rats to study the effect of pergolide, a mixed D1/D2 dopamine (DA) receptor agonist with predominant D2 action in vivo, on the biotransformation of endogenous and exogenous L-DOPA. Levels of L-DOPA, DA, DOPAC, HVA and 5-HIAA were measured by high performance liquid chromatography. Pergolide (50 micrograms/kg, i.p.) caused a 47%, 65% and 70% decrease in basal striatal extracellular (EC) levels of DOPAC, HVA and DA, respectively. L-DOPA (100 mg/kg, i.p.), injected 2 hours after carbidopa, produced significant increase in EC levels of L-DOPA, DOPAC, HVA and DA in rats with and without local perfusion of 10(-4) M pergolide. The DOPAC peak value was lower and was reached 60 minutes later in the group with pergolide. This study demonstrated inhibitory effects of pergolide on endogenous DA release and influence of pergolide on exogenous L-DOPA biotransformation.

Animals↗

Use of positron emission tomography (PET) in stereotactic conditions for brain biopsy.

In order to take advantage of the metabolic information provided by positron emission tomography (PET) in cases of brain tumour, we have developed a technique to integrate PET images routinely in the planning of stereotactic brain biopsy. We used stereotactic PET with [18F]-labelled fluorodeoxyglucose (PET-FDG) in 38 patients undergoing brain biopsy. To evaluate the contribution of PET-FDG in guiding brain biopsy, we analyzed the diagnosis provided by the 78 stereotactic trajectories obtained in these patients. We found that stereotactic PET-FDG seemed to provide more information in cases of anaplastic astrocytomas and glioblastomas than in low-grade gliomas. Our results also show that biopsy trajectories performed in areas where increased FDG uptake is found within the lesion boundaries always provide interpretable specimens; this was not the case for trajectories guided by CT only. Therefore, the routine integration PET-FDG in the planning of stereotactic brain biopsy may lead to a reduction in sampling. Recently, we also tested consecutive stereotactic PET with [11C]-labelled methionine (PET-Met) and PET-FDG. This technique allowed us to compare accurately the tumoural glucose metabolism and protein synthesis. Our results suggest that stereotactic PET may increase the diagnostic yield of brain biopsy and may improve the understanding of PET in neuro-oncology.

Adult↗

Use of cumulative meta-analysis in the design, monitoring, and final analysis of a clinical trial: a case study.

From 1983 to 1987, the Department of Veterans Affairs (DVA) Cooperative Studies Program (CSP) conducted a multicenter clinical trial (CSP #207) to determine whether four different antiplatelet regimens compared to placebo could prevent the occlusion of grafts following coronary artery bypass surgery. The study showed that all of the active regimens tended to be better than placebo and that the three regimens containing aspirin were statistically significantly better. A cumulative meta-analysis of 12 trials performed shortly before the end of CSP #207 raised the issue as to whether the meta-analysis, if done earlier, would have changed the conduct of the trial. At the start of the planning period, one trail of size n = 37 had been published with a nonsignificant odds ratio (OR) of 0.74 (95% CI: 0.18, 3.12). At the time that CSP # 207 was approved by the DVA Cooperative Studies Evaluation Committee, two trials had been published (cumulative n = 150, OR = 0.44, 95% CI 0.19, 0.99). At the time patient intake started, five trials showed cumulative n = 769, OR = 0.42, 95% CI = 0.26, 0.68. Although the first 6-month CSP #207 progress report showed no treatment effect, by the time of the 12-month review by the Data Monitoring Board (DMB) a trend was developing in favor of active treatment. If the results of the meta-analysis had been available to the DMB at that time, conceivably the Board would have recommended stopping the placebo arm because of a convincing treatment effect based on the totality of the evidence. Cumulative meta-analysis could be useful as an adjunct in the planning, conduct, and final analysis of a clinical trial. It could also be used as one piece of evidence in the monitoring of the ongoing phase of a trial.

Anti-Inflammatory Agents, Non-Steroidal↗

PET findings in a brain abscess associated with a silent atrial septal defect.

Brain abscesses are classical complications of congenital heart disease (CHD) in children and adolescents. This association is rarely observed in adults. We report a 46-year-old man presenting a fronto-parietal abscess associated with an asymptomatic atrial septal defect. Positron emission tomography (PET) study revealed high uptake of L-[methyl-11C]methionine ([11C]methionine) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) around the brain abscess. We suggest (1) to exclude a silent cardiac malformation in the presence of a cerebral abscess of unknown source occurring in adults; (2) to consider the diagnosis of brain abscess in cases of high uptake of [11C]methionine and FDG in relation to a brain lesion.

Biopsy↗

Stability of red blood cell membrane fatty acid composition after acute myocardial infarction.

Questionnaire-based assessment of dietary intake may be invalidated in case-control studies by biases of recall, reporting or interviewing. Biomarkers, free of such biases, can be useful adjunct measures if they themselves are not affected by the event under investigation. Consequently, we studied the stability of the fatty acid composition of the red blood cell (RBC) membrane during a 1-week period, in 20 patients aged 40-74 years after an acute myocardial infarction (MI). Statistical analysis that accounted for a repeated measures design with missing data was undertaken for five fatty acids: C16:0, C18:1, C18:2, C20:5 and C22:6. All fatty acids showed change over the 7 day period. Individuals tended to maintain their relative ranking over time as reflected by correlations between time points of between 0.85 to 0.90, with the exception of C16:0 in which correlations were lower and inconsistent. Over the first 24 hr from admission all fatty acids except C20:5 showed evidence of a statistically significant change. However over the first 7 hr C18:1, C18:2, C20:5 and C22:6 exhibited stability whereas C16:0 altered. We conclude that the fatty acid composition of the RBC membrane appears to change soon after an acute MI. Consequently, case-control studies may be biased towards positive associations for C16:0 and inverse associations for C18:2 and C20:5, i.e. consistent with conventional predictions. However, if blood samples are drawn within 6 hr of admission, bias in estimation of C18:1, C18:2, C20:5 and C22:6 may be unimportant.

Adult↗

The effects of race, household income, and parental education on nutrient intakes of 9- and 10-year-old girls. NHLBI Growth and Health Study.

Nutrient intakes of 2149 black and white, 9- and 10-year-old girls varied by race, household income, and parental education. Of the three variables, higher education was most consistently associated with more desirable levels of nutrient intakes, that is, lower percentage of dietary fat and higher levels of vitamin C, calcium, and potassium. Higher income was related to higher intakes of vitamin C, but lower intakes of calcium and iron. Higher income was associated with lower percentage of dietary fat. After adjustment for income and education, race was associated with intakes of calcium, vitamin C, and to a lesser extent, percentages of kilocalories from total fat and polyunsaturated fat, and potassium. Black girls had a significantly lower intake of calcium (720 versus 889 mg) and a higher intake of vitamin C (91 versus 83 mg). Proportions of the cohort with inadequate or excessive intakes of micronutrients and macronutrients were also estimated. A high proportion of girls exceeded the recommended intake level of 30% of kilocalories from total fat (90% of black girls; 84% of white girls) and 10% of kilocalories from saturated fat (92 and 93%, respectively). Low intakes of calcium (40% of black girls and and 20% og white girls) and zinc (36 and 38%, respectively) commonly were found for girls of both names.

Black or African American↗

Rat infarct model of myocardial infarction and heart failure.

This review outlines the development and current use of the rat coronary artery ligation model of heart failure. The techniques to ligate the left coronary artery and to obtain morphologic/hemodynamic measurements are described. The authors show how the pathology seen in this model relates to clinical ischemic heart disease. An effort is made throughout the review to relate the changes that occur in this model to clinically relevant observations. For example, the progression to heart failure in these rats is similar to what happens when a patient sustains a large myocardial infarction, survives, but goes on to develop heart failure without another ischemic insult. In both rats and people with large infarctions, the noninfarcted myocardium, even though not damaged at the time of the infarct, cannot compensate sufficiently to prevent the eventual development of heart failure. In addition to being a good approximation of human disease, the responses to pharmacologic interventions, like angiotensin converting enzyme inhibitors, in rats has proved useful in predicting what will happen in humans given the same treatment. More recent data on the molecular control of ventricular remodeling emphasizes how this model will provide important information in the study of integrated physiology by examining biochemical, pharmacologic, and physiologic changes in the same tissue.

Adrenergic Antagonists↗

Ambulatory phlebectomy using the tumescent technique for local anesthesia.

BACKGROUND: Ambulatory phlebectomy is a cosmetically elegant procedure that provides outpatient office-based surgical removal of large truncal varicose veins. The process of local anesthetic infiltration using traditional means is a time-consuming process that can be painful, and carries with it the inherent risk of accidental intravascular injection. OBJECTIVE: To introduce the tumescent technique for local anesthesia as it relates to the procedure of ambulatory phlebectomy and discuss the benefits of this form of anesthesia. METHODS: A description of the technique utilizing a dilute anesthetic solution, an injection syringe, and blunt-tipped anesthetic probe is provided. RESULTS: Using the tumescent technique for local anesthesia, large areas can be anesthetized quickly, safely, effectively, and relatively painlessly, offering multiple advantages over simple local infiltration, and eliminating the need for regional or general anesthesia. CONCLUSION: The authors consider the tumescent anesthesia technique to be highly effective and an important adjunct to the procedure of ambulatory phlebectomy.

Ambulatory Surgical Procedures↗

Basal ganglia and frontal lobe glucose metabolism. A reproducibility positron emission tomography study.

Positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) is frequently used to study the metabolic correlates of movement and mental disorders. These studies generally focus on changes in the frontal cortex and the basal ganglia. The reproducibility of glucose metabolism estimates in these structures was tested in 13 normal subjects studied at rest using a standard and simple protocol. A reproducible dorsoventral metabolic gradient was demonstrated in the frontal cortex. Such a gradient was not present in the basal ganglia when the upper region of interest in the caudate nucleus, where the lower metabolic rate of glucose was probably attributable to partial volume effects, was not considered. Absolute values of glucose metabolic rates varied by 6.4 to 12.5% in the frontal cortex and by 6.8 to 14.7% in the basal ganglia. Variations in normalized values in the basal ganglia ranged from 4.0 to 8.6%. The number of subjects required to detect statistical differences in group comparison or in test-retest studies was calculated for different anticipated levels of change. With the variability detected in this experiment, less than 10 subjects were expected to be sufficient to detect a 15% change in most regions and in both types of studies.

Adult↗

Changes in metabolism of cerebral glucose after stereotactic leukotomy for refractory obsessive-compulsive disorder: a case report.

Brain glucose metabolism was investigated with PET and [18F]fluorodeoxyglucose, before and after a bifrontal stereotactic leukotomy in a 37 year old woman with refractory obsessive-compulsive disorder. A bilateral decrease in glucose metabolism was found in the orbital frontal cortex after psychosurgery. Glucose metabolism was decreased to a lesser degree in Brodmann's area 25, in the thalamus, and in the caudate nucleus. Clinical improvement in obsessive-compulsive disorder after stereotactic tractotomy seems to be associated with metabolic changes in the brain, in particular, in the orbital part of the frontal lobe.

Adult↗

Alien hand syndrome without a corpus callosum lesion.

A 58 year old right handed woman developed a left alien hand syndrome after a right capsulothalamic haemorrhage with mesencephalic extension. No lesion was detected in the corpus callosum. Positron emission tomography suggested that right cortical dysfunction might account for the absence of recognition of the left hand whereas involuntary motor activity was attributed to the lesion itself. This case shows that the alien hand syndrome is not always the expression of a disconnection syndrome and may occur after a large, strategically located, posterior lesion.

Corpus Callosum↗

Large artery remodeling after myocardial infarction.

Rats with myocardial infarction (MI) after coronary artery ligation (n = 75) and sham operated rats (n = 40) were treated with captopril (2 g/l drinking water), hydralazine (80 mg/l drinking water), or untreated water for 3 wk. Arterial hemodynamics, carotid artery mechanical properties, and water permeability were measured. Arterial wall stress and interstitial fluid velocity were calculated. In infarcted rats, the characteristic impedance at matched pressure was increased by 135% (P < 0.02); captopril and hydralazine decreased characteristic impedance (P < 0.015). MI altered the material constants; captopril but not hydralazine normalized these constants. Water permeability was increased by 221% (P < 0.001) in infarcted rats; captopril but not hydralazine reversed water permeability (P < 0.05). MI resulted in a 59% increase (P < 0.05) in the arterial collagen area and a 22% decrease (P < 0.05) in the media thickness. Captopril but not hydralazine decreased (P < 0.03) collagen area. In conclusion, 1) arterial remodeling defined by alterations in the passive mechanical properties, water permeability, and structure occurs in rats after MI; and 2) captopril but not hydralazine reverses the arterial remodeling.

Animals↗

Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts.

In most studies, aspirin has been shown to be effective for a period of 1 year in reducing the frequency of saphenous vein bypass graft occlusion when begun 1 day before surgery, on the day of surgery, or the day after surgery. Effective doses of aspirin range from 100 to 975 mg/d. Aspirin in combination with dipyridamole is effective in the prevention of saphenous vein bypass graft occlusion if aspirin and dipyridamole therapy is started 1 or 2 days before surgery or aspirin therapy is started on the day of surgery but dipyridamole therapy is started before surgery or if treatment with both aspirin and dipyridamole is started 1 day after surgery. Aspirin in combination with dipyridamole is not more effective than aspirin alone in the prevention of saphenous vein graft occlusion. Bleeding is higher among patients treated with aspirin alone than among controls if aspirin therapy is started 1 day before surgery. Bleeding is not greater in comparison to controls if aspirin therapy is started the day of surgery or 1 day after surgery. When aspirin and dipyridamole are used in combination, bleeding is higher than in controls, and bleeding is higher than with aspirin alone. The continued use of aspirin for 2 additional years after an initial year of aspirin therapy for the prevention of saphenous vein bypass graft occlusion showed no additional long-term benefit on graft patency at the end of the third year.

Clinical Trials as Topic↗