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Biomedical subjects

R Levy

Publications and source records attributed to R Levy.

At least 415 records · Page 23Linked to original sources

Morphologic (CT) and functional (rCBF-SPECT) correlates in Alzheimer's disease.

Thirty-five patients with a clinical diagnosis of probable Alzheimer's disease underwent computed tomography (CT) and regional cerebral blood flow (rCBF) studies using single photon emission computed tomography (SPECT). Two sets of images in each subject were scored for the extent of structure and function changes. Thirty-four of 35 patients had various degrees of atrophy on CT, 33 of whom also had perfusion deficits of varying severity. One patient with normal CT had perfusion deficits, and another patient with a normal perfusion pattern had changes on CT. Regional perfusion deficits on SPECT were seen with and without associated changes on CT. Correlations were studied between CT and SPECT scores using Spearman's rank correlation coefficients. While regional scores on CT and SPECT did not significantly correlate, the total and left hemisphere scores on two sets of images showed fair correlations (r = 0.425 and r = 0.535, respectively, P less than 0.01). The correlations between cognitive performance in patients as assessed on Mini-Mental State Examination (MMSE) and CAM-COG and perfusion scores were highly significant while CT scores showed lower correlations. These findings suggest that the relationship between structural and functional changes in Alzheimer's disease is not straightforward and that the extent of changes in function as assessed by regional cerebral blood flow studies is a reliable measure of deficits in cognitive function.

Aged↗

Patterns of regional cerebral blood flow in Alzheimer's disease.

Regional cerebral blood flow was assessed in 35 patients with Alzheimer's disease and the same number of matched normal volunteers. Images were scored for regional perfusion deficits. Mildly demented patients had parietal and temporal perfusion deficits, often unilateral. Moderate to severely demented patients had bilateral temporal and parietal perfusion deficits. All severely demented patients also had involvement of both occipital regions. Frontal lobe deficits were seen in 14 patients. Left cortical perfusion deficits were more severe than the right cortical perfusion deficits in general. Patients with early onset of the disease showed left frontal deficits, more often, however, the total perfusion deficit scores in early and late onset groups were not statistically significant. Also, the cognitive performance scores were not statistically significant in these two groups. These results suggest a stage-dependent reduction in regional cerebral blood flow in patients with Alzheimer's disease.

Aged↗

Quantification of regional cerebral blood flow (rCBF) using 99Tcm-HMPAO and SPECT: choice of the reference region.

The effects of the choice of the reference region in determining the relative regional cerebral blood flow (rCBF) using 99Tcm-hexamethylpropylene amine oxime (HMPAO) single photon emission tomography (SPECT) have been studied in order to establish or exclude it as a cause of inconsistencies in these studies. Relative rCBF was estimated by normalizing the regional count densities to two reference regions, the cerebellum and the whole slice, in 35 patients with Alzheimer's disease (AD), 25 patients with chronic schizophrenia (SCH) and the same number of matched normal volunteers. The statistical significance of the differences in rCBF between patients and their matched normals varied in the two sets of rCBF data. Smaller differences were highly significant while some larger differences were of less significance with whole slice normalization. The results suggest that the choice of reference region is one of the causes resulting in discrepancies in the results from various centres. The need to use a standard reference region is indicated.

Alzheimer Disease↗

Efficacy of varicocele embolization versus ligation of the left internal spermatic vein for improvement of sperm quality.

Efficacy of surgical varicocelectomy versus embolization of the spermatic vein was studied in 137 men diagnosed as suffering from left varicocele. The men were divided randomly into three groups according to the methods of treatment: A--embolization of the internal spermatic vein (51 men); B--Ivanissevich technique of high ligation of the spermatic veins (43 men); and C--Bernardi technique of high ligation (43 men). The groups were similar in terms of age, duration of infertility and possessed semen characterized as oligoteratoasthenozoospermia. The fertility of the female partners was evaluated carefully and they were found to be potentially fertile. Varicocele was diagnosed by at least two of the following methods: physical palpation during valsalva manoeuvre, venography, or scrotal scanning using the technetium pertechnetate radioactive method. Semen quality was assessed before treatment and at 3, 6 and 9 months post-treatment. Fecundity was followed-up for 18 months. The major results were: (i) Shrinkage of the varicocele was found in all three groups studied. The same rate of recurrence was recorded in the three groups (24%, 37% and 35% in groups A, B and C, respectively). (ii) Improvement of sperm quality was significant in groups A and B, with better results in group B. (iii) The pregnancy rate was significantly higher in group B, compared with A (38.2% vs. 20.6%; P less than 0.05). Thus, high ligation of the internal spermatic vein yields better results than low ligation or embolization as far as semen quality and pregnancy is concerned.

Embolization, Therapeutic↗

A study of regional cerebral blood flow and cognitive performance in Alzheimer's disease.

Thirty five patients with dementia of the Alzheimer type (DAT) and 35 controls matched for age, sex and handedness were investigated using single photon emission computer tomography (SPECT) with 99m technetium HMPAO. Regional cerebral blood flow (rCBF) was assessed semi-quantitatively in 18 cortical and 4 subcortical areas by normalising mean information density in each region to cerebellar mean information density. Analysis revealed significantly reduced rCBF to temporal, parietal, frontal and left occipital cortex in the patients whilst blood flow to subcortical areas showed no differences between the 2 groups. In addition, significant left-sided cortical hypoperfusion was seen in the DAT group but not in controls. When patients were sub-divided on the basis of disease severity, those with mild disease showed temporal, parietal and left frontal changes with more severely affected patients also showing right frontal and left occipital involvement. rCBF patterns did not distinguish between presenile and senile onset cases once duration and severity of illness were controlled. Eight cortical areas were also rated visually for perfusion deficits on a simple 4 point scale. Perfusion deficits were detected in 34 of 35 patients but in only 4 of 35 controls. In the DAT group significant correlations were found between many of the neuropsychological tests used and rCBF. Memory correlated with left temporal activity, praxis, perception, object assembly and block design with right parietal activity and language with activity throughout the left hemisphere. Significant correlations were also seen between subcortical and cortical blood flow, possibly explaining the correlations observed between many of the neuropsychological tests and thalamic blood flow.

Aged↗

Tacrine in Alzheimer's disease. Time course of changes in cognitive function and practice effects.

This paper concerns certain questions which arose during the analysis of a trial showing positive effects of tacrine in Alzheimer's disease. Cognitive improvement occurred during the first two weeks, reached a maximum at one month and was maintained during the rest of the three-month treatment period. Rebound effects were not detected in any of the key outcome variables, but were suggested by one of the supporting cognitive tests and other measures. Practice effects occurred on tests which were repeated at short intervals or too frequently. The paper discusses the significance of these findings for the interpretation of other trials and for practical management.

Aged↗

High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin's disease.

PURPOSE: For patients with Hodgkin's disease (HD) who do not achieve complete response (CR), who experience a relapse within the first year of CR, and for those who have two or more relapses, the outcome is poor. Salvage chemotherapy regimens at conventional doses produce a CR rate that ranges from 10% to 50% and a 5-year disease-free survival (DFS) between 10% and 25%. On the other hand, high-dose chemotherapy regimens given in combination with bone marrow transplantation (BMT) produce a CR rate that ranges from 40% to 80% and a 3-year DFS of approximately 40%. We report the 5-year results of a prospective study in patients with refractory HD who were treated with three courses of intensive chemotherapy without BMT. PATIENTS AND METHODS: Thirty-nine adult patients with refractory HD were treated with three courses of intensive chemotherapy. Each cycle of chemotherapy comprised vindesine 1 mg/m2/d in continuous intravenous (IV) infusion from day 1 to day 5; Adriamycin (doxorubicin; Roger Bellon Laboratories, Neuilly, France) 40 mg/m2/d in continuous IV infusion from day 1 to day 3; carmustine 140 mg/m2/d at day 3; etoposide 200 mg/m2/d from day 3 to day 5; and methylprednisolone 120 mg/m2/d from day 1 to day 5. After the third cycle of chemotherapy, irradiation (20 Gy) was performed whenever possible and depended on previous irradiation. RESULTS: At the end of the treatment, 31 patients (79%) were in CR. Among these patients, 10 relapsed after a median time of 3 months. The overall 5-year survival rate was 46%. The freedom from progression (FFP) and the freedom from treatment failure (FFTF) rates were 48% and 43%, respectively. The main toxicities were hematologic (neutropenia and thrombocytopenia) and digestive. Four patients died due to treatment-related complications (two from septic shocks, one from respiratory insufficiency, and one from posttransfusional AIDS). CONCLUSION: The results of this study seem to be comparable to those results obtained with high-dose chemotherapies with autologous BMT.

Adolescent↗

[Biology of small-cell bronchogenic carcinoma: recent advances].

In the last ten years considerable progress has been made in small-cell lung carcinoma (SCLC) biology, along with the technical progress made in molecular biology. This progress now allows us to propose a model for the genesis and the development of this type of tumor. Tobacco, the principal causal factor plays a dual role. In bringing about secretion of growth factors by the bronchial epithelia, usually involved in the normal development of lungs, and by functioning autocrinally and paracrinally, it facilitates the occurrence of mitotic mutations. Without directly contributing to cellular transformation, this autocrine functioning also gives a selective advantage to cells going through transformation or immortalization. The procarcinogenic or carcinogenic agents contained in tobacco smoke, whose level of production could be genetically determined, would also contribute to the accumulation of mutations affecting both suppressor genes and oncogenes. Two tumour suppressor genes have been identified: RB1 and P53. At least one other putative tumour suppressor gene has constantly been implied. It lies on the short arm of chromosome 3. There could also be the possibility of detecting subjects susceptible to developing an SCLC, a functional hemizygote still needing evaluation. The activated oncogenes principally belongs to the myc family. Their activation could correspond with the appearance of cellular clones having aggressive behavior independent of growth factors, chemoresistant and more metastatic. SCLC may be distinguished from other malignant lung tumors by a fairly characteristic pattern consisting of the loss of suppressor genes and the activation of oncogenes. The links between the neuroendocrine properties of this type of tumor and its characteristic description are being clarified and will contribute to a better understanding of the relationship between the different types of lung tumors. From this biologic knowledge follow several therapeutic applications under investigation (blocking autocrine loop through anti-GRP antibodies), as well as potential applications (concerning the products of suppressor genes) and possible applications such as prevention oriented towards detection of high-risk subjects.

Carcinoma, Bronchogenic↗

[Organic correlates of depressive symptoms in Alzheimer's dementia. Results of a prospective study, review of the literature].

The diagnosis of Alzheimer's disease (AD) was verified at post-mortem examination in 46 patients (9 male: 37 female; mean age 83.6 +/- 6.5 years) from a prospective clinical study. Compared to 10 age-matched controls, the total AD group showed a significant neuronal loss in the locus coeruleus, dorsal raphe nucleus, substantia nigra and in the basal nucleus of Meynert. Twelve patients (1 male: 11 female) had experienced symptoms of depression. These patients had significantly lower neuronal counts in the locus coeruleus, but less severe cell loss in the basal nucleus of Meynert compared to the AD patients without depression.

Aged↗

Cholesteryl ester storage disease: complex molecular effects of chronic lovastatin therapy.

To better characterize the in vivo effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition on human lipid metabolism, an adolescent male with cholesteryl ester storage disease (CESD) was treated chronically with lovastatin. Therapy was associated with decreased liver-spleen size, improved but not normal serum lipids, a 26% decrease in hepatic cholesteryl ester, a 12% decrease in unesterified hepatic cholesterol, and a fourfold increase in hepatic low density lipoprotein (LDL) receptor protein. Hepatic mRNA levels for the LDL receptor and apolipoprotein (apo) B standardized to levels of hepatic gamma actin mRNA were unchanged with therapy. Kinetic studies revealed no change in the LDL fractional catabolic rate and a decrease in the LDL production rate. Size exclusion chromatography showed striking reductions in plasma very low density lipoprotein (VLDL) cholesterol and intermediate density lipoprotein (LDL) cholesterol but not LDL cholesterol with therapy. Mean LDL particle size and the LDL particle size range were increased by treatment. However, there was no difference in the ability of pretreatment or treatment LDL to bind to the LDL receptor on cultured cells consistent with previous studies in animals, indicating that lovastatin may alter LDL particles to impair interaction with the LDL receptor in vivo but not in vitro. Lovastatin therapy in CESD appears to be clinically beneficial and has complex effects on lipid metabolism that may include a dominant inhibitory effect on hepatic lipoprotein production, posttranscriptionally mediated induction of the LDL receptor, and alterations of LDL particles that interfere with their clearance by the LDL receptor in vivo.

Actins↗

Imaging and affective disorder in the elderly.

Changes in brain structure have been demonstrated in elderly patients suffering affective disorder. Enlarged ventricles are associated with cognitive impairment and higher mortality. Depressed subjects also may show a greater degree of cortical atrophy and subcortical white matter, and basal ganglia lesions seem to be commoner than in age-matched controls. The abnormalities demonstrated are not as severe as those found in degenerative dementias such as Alzheimer's disease, and at present there is no evidence to suggest they are progressive. There is a convincing association with vascular disease, although further neuropathologic correlates are needed. Functional imaging methods are just beginning to be applied to elderly populations and, in affective disorder, findings are similar to those in younger patient groups. The results from different groups vary due to technologic differences and the clinical heterogeneity of the patients studied. Depression, however, may be accompanied by decreased and mania by increased cerebral blood flow or metabolism. Evidence also appears to be mounting of a state-dependent frontostriatal dysfunction in depression. Challenges for the future include replicating such results using larger diagnostically homogeneous patient groups and differentiating the findings from those in other disorders such as schizophrenia and basal ganglia disorders.

Aged↗

Diversity of T-cell antigen receptor variable genes used by mycosis fungoides cells.

The expression of T-cell antigen receptor beta-chain variable genes (V beta) was evaluated in 28 cases of mycosis fungoides. A novel polymerase chain reaction (PCR) technique was used to associate expression of particular V beta genes with monoclonal T-cell populations. In addition, the same biopsies used for PCR analysis were also examined for reactivity with a panel of seven monoclonal antibodies that specifically recognized V beta proteins from four different families. Only three cases clearly stained with the antibodies, a result consistent with a diverse set of V beta genes being used. This was confirmed by PCR analysis, which indicated that V beta genes from many different families were expressed by these tumors. Preferential use of the V beta 8 family, which had been previously use of the V beta 8 family, which had been previously reported for this disease, was not evident among the cases analyzed.

Antibodies, Monoclonal↗

Acute limited normovolemic hemodilution can be safely used in a malnourished model.

This study investigates the effects of acute limited normovolemic hemodilution (ALNH) on intestinal healing in a malnourished animal model. Twenty rabbits were randomized into three Groups: Group 1 = control; Group 2 = ALNH (removal 35% blood volume and maintenance of normovolemia with 3:1 crystalloid infusion) followed by retransfusion (RT) after small bowel anastomosis (ANA). Group 3 had a restricted diet for 3 weeks preoperatively to cause a 15 percent to 20 percent weight loss. A six cm segment of small bowel (SB) was resected and anastomosed (ANA) in all animals. Blood pressure (BP), transserosal oxygen tension (TsPao2), hematocrit (Hct), colloid oncotic pressure (COP), wet-to-dry weight ratios (WW/DW), hydroxyproline (OH-Pro) content, and tensile strength (TS) of the ANA and a segment of adjacent SB were determined. BP did not change from baseline (BL) in Group 2 during ALNH; however, it rose significantly after RT (P less than 0.05). BP decreased significantly during ALNH in Group 3 (P less than 0.05) and did not rise above baseline after RT. There was no significant change in TsPao2 from BL within groups during the experiment. The Hct and COP decreased significantly after ALNH in Groups 2 and 3 after ALNH compared to BL (P less than 0.05). After RT the Hct and COP increased and by Day 8 the Hct had risen to BL values in Group 3 but not in Group 2 (P less than 0.05), whereas COP values were not significantly different from BL in either group. There was no difference in WW/DW or TS between or among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

Pericardiotomy improves left ventricular compliance during sepsis-induced pulmonary artery hypertension.

Sepsis-induced pulmonary artery hypertension (SIPAH) causes an increase in right ventricular (RV) afterload, dilatation of the RV, leftward shift of the interventricular septum (IVS), and therefore decreases left ventricular compliance (LVC). This study was designed to evaluate the role of pericardiotomy during SIPAH as an alternative to vasodilators (which cause a detrimental increase in shunt fraction) to improve LVC. Systemic and pulmonary hemodynamics, pulmonary function, RV, and LVC were acquired at baseline (BL), during SIPAH with closed pericardium (PAHCP) and after opening the pericardium (PAHOP). Systemic hemodynamics and pulmonary function did not change significantly during the experiment. The infusion of live bacteria induced a significant rise in mean pulmonary artery pressure from 16 +/- 5.3 at BL to 36.8 +/- 3.3 and 35.0 +/- 6.4 mm Hg during PAHCP and PAHOP, respectively, (P less than 0.05). Pulmonary vascular resistance index and right ventricular stroke work index (RVSWI) displayed a similar rise in response to SIPAH (P less than 0.05 vs BL). Pericardiotomy did not affect pulmonary hemodynamics or RVSWI. Right ventricular contractility did not increase following pulmonary hypertension while the pericardium was closed (440 +/- 78 vs 410 +/- 125, P less than 0.05); however, it rose, although not significantly, to 615 +/- 326 after pericardiotomy. RV time tension index displayed a rise during SIPAH with the pericardium intact and returned to baseline values after pericardiotomy; however, these changes were not significant. RVC did not change significantly throughout the experiment. In contrast, LVC decreased significantly after SIPAH and significantly improved after pericardiotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗