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K Rezai

Publications and source records attributed to K Rezai.

At least 19 recordsLinked to original sources
PubMed2006

Variations in schedules of ifosfamide administration: a better understanding of its implications on pharmacokinetics through a randomized cross-over study.

PURPOSE: The metabolism of ifosfamide is a delicate balance between a minor activation pathway (4-hydroxylation) and a mainly toxification pathway (N-dechloroethylation), and there remains uncertainty as to the optimal intravenous schedule. METHODS: This study assesses ifosfamide pharmacokinetics (PK) according to two standard schedules. Using a 1:1 randomized trial design, we prospectively evaluated ifosfamide PK on two consecutive cycles of 3 g/m2/day for 3 days (9 g/m2/cycle) given in one of two schedules either by continuous infusion (CI) or short (3 h) infusion. Highly sensitive analytical methods allowed determination of concentrations of ifosfamide and the key metabolites 4-hydroxy-ifosfamide, 2- and 3-dechloroethyl-ifosfamide. RESULTS: Extensive PK analysis was available in 12 patients and showed equivalence between both schedules (3 h versus CI) based on area under the curves (micromol/l x h) for ifosfamide, 4-hydroxy-ifosfamide, 2- and 3-dechloroethyl-ifosfamide (9,379 +/- 2,638 versus 8,307 +/- 1,995, 152 +/- 59 versus 161 +/- 77, 1,441 +/- 405 versus 1,388 +/- 393, and 2,808 +/- 508 versus 2,634 +/- 508, respectively, all P > 0.2). The classical auto-induction of metabolism over the 3 days of infusion was confirmed for both schedules. CONCLUSION: This study confirms similar PK for both active and toxic metabolites of ifosfamide in adult cancer patients when 9 g/m2 of ifosfamide is administered over 3 days by CI or daily 3-h infusions.

Adult↗
PubMed2005

Development of Daptomycin resistance in vivo in methicillin-resistant Staphylococcus aureus.

Daptomycin is a new lipopeptide antibiotic that is rapidly bactericidal against Staphylococcus aureus. We report daptomycin resistance and treatment failure in 2 patients with osteomyelitis due to methicillin-resistant S. aureus. Disk diffusion susceptibility testing failed to detect resistance. Daptomycin at high concentration retained bactericidal activity against resistant isolates.

Aged↗
PubMed2001

Factors influencing visualization of vertebral metastases on MR imaging versus bone scintigraphy.

OBJECTIVE: The purpose of this study was to investigate whether the location and size of vertebral body metastases influence the difference in detection rates between MR imaging and bone scintigraphy. MATERIALS AND METHODS: We retrospectively evaluated the vertebral body lesions detected on MR imaging in 74 patients with known widely disseminated metastatic disease. Three radiologists independently reviewed the MR images and bone scintigraphs. MR imaging findings included lesion size and its spatial relationship to the bony cortex (intramedullary, subcortical, and transcortical) and results were correlated with those of planar technetium 99m bone scintigraphy. RESULTS: Findings on bone scans were negative for all intramedullary lesions without cortical involvement shown on MR imaging, regardless of their size. Findings on bone scans (71.3% for transcortical and 33.8% for subcortical) were frequently positive for lesions with cortical involvement (trans- or subcortical), and the probability of positive findings on bone scans was also influenced by the lesion size. Statistical analysis showed a positive correlation among cortical involvement, lesion size, and positive findings on bone scintigraphy (p < 0.0001). CONCLUSION: Location (the presence of cortical bone involvement on MR imaging) and size of the vertebral body metastases appear to be important contributing factors to the difference in detection rates between MR imaging and bone scintigraphy. Cortical involvement is likely the cause of positive findings on bone scans. Early vertebral metastases tend to be small and located in the medullary cavity without cortical involvement, and therefore, findings may be positive on MR images but negative on bone scans.

Female↗
PubMed1997

The effect of antipsychotic medication on relative cerebral blood perfusion in schizophrenia: assessment with technetium-99m hexamethyl-propyleneamine oxime single photon emission computed tomography.

Functional neuroimaging studies in schizophrenia have often been confounded by various factors including medication status. To explore the effects of antipsychotic medications on relative regional cerebral perfusion, we scanned a group of 33 persons with schizophrenia twice, while receiving a stable dose of antipsychotic and after being off antipsychotics for 3 weeks, using technetium-99m hexamethyl-propyleneamine oxime single photon emission computed tomography (Tc-99m HMPAO-SPECT. We found that antipsychotic significantly increased the mean relative cerebral perfusion in the left basal ganglia. Additionally, patients receiving thiothixene (n = 9) had a significantly greater increase in relative cerebral perfusion in the basal ganglia than patients receiving haloperidol (n = 12). These findings indicate that antipsychotics lead to regional increases in cerebral perfusion and that antipsychotic status must be controlled for in functional neuroimaging studies. Functional neuroimaging techniques such as SPECT may be useful in furthering our understanding of the mechanism of antipsychotics.

Adult↗
PubMed1997

Effect of antipsychotics on regional cerebral blood flow measured with positron emission tomography.

Positron Emission Tomography (PET) imaging of regional cerebral blood flow (rCBF) provides an in vivo method for studying brain function. We used [15O]H20 PET to assess the effect of antipsychotic medications on rCBF in 17 subjects with schizophrenia. Each subject was scanned while receiving antipsychotic medication, and after having been withdrawn from antipsychotic medication for a 3-week period. The two scans were subtracted from one another, using a within subjects design, and the areas of difference were identified using the Montreal method. Subjects treated with antipsychotic medication had significantly higher rCBF in the left basal ganglia and left fusiform gyrus compared with the "off-medication" condition. Significantly higher relative rCBF in the anterior cingulate, left dorsolateral and inferior frontal cortex, and left and right cerebellum was observed when off antipsychotic medication. Upregulation of dopamine D2 receptors may lead to a regional increase of blood flow and metabolism in the basal ganglia, which may explain recently reported anatomical enlargement in these regions.

Adolescent↗
PubMed1996

Evaluation of diabetic patients for renal and pancreas transplantation: noninvasive screening for coronary artery disease using radionuclide methods.

Pharmacologic stress thallium scintigraphy is commonly performed in the risk assessment of diabetic patients with nephropathy before kidney and/or pancreas transplantation; however, controversy exists regarding the test's accuracy in detecting coronary artery disease. Our purpose was to compare pharmacologic stress thallium scintigraphy and also exercise radionuclide ventriculography with coronary angiography in diabetic patients undergoing evaluation for transplantation. In addition, we also determined the association of the test results with outcome after transplantation. The medical records of 47 patients (mean age, 37+/-9 years) without clinical evidence of coronary artery disease were reviewed. Forty-one patients had pharmacologic stress thallium scintigraphy performed during their evaluation. Sensitivity was 62% and specificity was 76% for detecting > or = 75% coronary artery stenosis (sensitivity was 53% and specificity was 73% for > or = 50% stenosis). Thirty-five patients had exercise radionuclide ventriculography performed. Sensitivity was 50% and specificity was 67% for detecting > or = 75% coronary artery stenosis (sensitivity was 44% and specificity was 63% for > or = 50% stenosis). Thirty patients had both pharmacologic stress thallium scintigraphy and exercise radionuclide ventriculography performed; when either test was abnormal, sensitivity in the detection of > or = 50% or > or = 75% stenosis tended to increase compared with pharmacologic stress thallium scintigraphy alone (0.05<P<0.10), whereas specificity decreased (P<0.01). The incidence of adverse cardiac outcomes was identical for patients with abnormal thallium scintigrams and undergoing transplantation (2/11) compared with patients with normal scintigrams and undergoing transplantation (4/22). We conclude that: (1) pharmacologic stress thallium scintigraphy and exercise radionuclide ventriculography are suboptimal screening tests for coronary artery disease in diabetic patients awaiting kidney and/or pancreas transplantation; (2) using the two radionuclide tests in combination results in a decrease in specificity; and (3) patients with abnormal thallium scintigrams can receive transplants with outcomes similar to those for patients with normal thallium scintigrams.

Adult↗
PubMed1996

Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry.

Patients suffering from schizophrenia display subtle cognitive abnormalities that may reflect a difficulty in rapidly coordinating the steps that occur in a variety of mental activities. Working interactively with the prefrontal cortex, the cerebellum may play a role in coordinating both motor and cognitive performance. This positron-emission tomography study suggests the presence of a prefrontal-thalamic-cerebellar network that is activated when normal subjects recall complex narrative material, but is dysfunctional in schizophrenic patients when they perform the same task. These results support a role for the cerebellum in cognitive functions and suggest that patients with schizophrenia may suffer from a "cognitive dysmetria" due to dysfunctional prefrontal-thalamic-cerebellar circuitry.

Adult↗
PubMed1996

Effects of leflunomide and other immunosuppressive agents on T cell proliferation in vitro.

Leflunomide and its active metabolite, A771726, are structurally unrelated to immunosuppressive agents currently under investigation. Previous in vitro studies have revealed that leflunomide primarily inhibits interleukin-2-stimulated T cell proliferation. In the current study, we have extended our previous work and demonstrate that leflunomide prevents T cell progression induced by phytohemagglutinin into the S phase of the cell cycle. To discriminate further the action on T cells of leflunomide from other immunosuppressive agents, we performed kinetic studies where leflunomide was added either after the initiation of mixed lymphocyte cultures (MLC) or after interleukin-2 stimulation of CTLL-4 cell proliferation. These studies revealed that leflunomide acted comparably to rapamycin, but was distinct from brequinar sodium in the MLC, and from cyclosporine and mycophenolic acid in both MLC and CTLL-4. Although previous biochemical studies indicated that leflunomide can inhibit src-family tyrosine kinase activity, more recent studies have suggested that leflunomide can also inhibit pyrimidine synthesis. Our data demonstrate that the ability of leflunomide (25-100 microM) to inhibit MLC and CTLL-4 cell proliferation is partially antagonized by uridine (25-100 microM), and support the hypothesis that leflunomide inhibits pyrimidine synthesis in T cells. Unique molecular mechanisms of immunosuppression suggest that drug combinations may result in synergistic immunosuppression. Our in vitro studies revealed synergistic inhibition of T cell proliferation with the combinations of leflunomide with cyclosporine or with rapamycin. We have extended those studies to quantitate inhibition of MLC by the combinations of leflunomide and brequinar sodium or mycophenolic acid.

Cell Division↗
PubMed1996

Neural substrates of facial recognition.

Seventeen healthy normal volunteers performed three facial recognition tasks while their cerebral blood flow was measured with PET: categorizing faces according to gender, recognizing new faces, and recognizing familiar faces. These tasks activated three different pathways: respectively, the left inferior temporal lobe and left frontal cortex; a predominantly right frontal-right parietal-left cerebellar network; and left lingual and left and right fusiform gyri. These results suggest that humans use different brain regions in performing these three routine daily activities. The results are consistent with previous observations concerning organization of extrastriate visual cortex in human and nonhuman primate lesion studies, including studies of the unusual syndrome of prosopagnosia (loss of the ability to recognize familiar faces with intact ability to recognize a face as a face).

Adult↗
PubMed1996

Four- to twenty-four-hour uptake ratio: an index of rapid iodine-131 turnover in hyperthyroidism.

UNLABELLED: Rapid thyroidal iodine turnover may contribute to 131I therapy failure in patients with hyperthyroidism. The utility of a 4- to 24-hr 131I uptake ratio was evaluated as an index of thyroidal iodide retention in hyperthyroid patients. METHODS: In 433 hyperthyroid patients, the success of 131I therapy was correlated with the following factors: gender, pretreatment with antithyroid drugs, clinical diagnosis, magnitude of early and late thyroidal 131I uptake values, and the 4- to 24-hr 131I uptake ratio. RESULTS: Of the 433 patients, 362 patients (84%) had a successful outcome after a single therapeutic dose of 131I while 71 (16%) did not. Multiple linear regression analysis revealed that the highest statistically significant predictor of outcome was the 4- to 24-hr 131I uptake ratio (p-value < 0.001); all other factors showed a weaker association. An 131I uptake ratio of > 1 was found in 67 (15%) patients. Thirty-two of these 67 patients (48%) failed 131I therapy, whereas those patients with uptake ratios of < 1.0, only 39/366 (11%) failed 131I therapy. CONCLUSION: The 4- to 24-hr 131I thyroidal uptake ratio is a practical substitute for exact determination of the effective half-life. It identifies patients who are likely to have a rapid 131I turnover without the need for extended thyroid uptake measurements. An 131I uptake ratio of > or = 1 was found in 15% of hyperthyroid patients and was associated with a near 50% 131I therapy failure rate.

Adult↗
PubMed1995

Short-term and long-term verbal memory: a positron emission tomography study.

Short-term and long-term retention of experimentally presented words were compared in a sample of 33 healthy normal volunteers by the [15O]H2O method with positron emission tomography (PET). The design included three conditions. For the long-term condition, subjects thoroughly studied 18 words 1 week before the PET study. For the short-term condition, subjects were shown another set of 18 words 60 sec before imaging, with instructions to remember them. For the baseline condition, subtracted from the two memory conditions, subjects read a third set of words that they had not previously seen in the experiment. Similar regions were activated in both short-term and long-term conditions: large right frontal areas, biparietal areas, and the left cerebellum. In addition, the short-term condition also activated a relatively large region in the left prefrontal region. These complex distributed circuits appear to represent the neural substrates for aspects of memory such as encoding, retrieval, and storage. They indicate that circuitry involved in episodic memory has much larger cortical and cerebellar components than has been emphasized in earlier lesion studies.

Adult↗
PubMed1995

I. PET studies of memory: novel and practiced free recall of complex narratives.

Positron Emission Tomography (PET) with the tracer H215O was used to measure regional cerebral blood flow in 13 healthy volunteers during two experimental memory tasks, one of which was well-practiced and the other of which was novel. The materials used for the memory tasks consisted of two complex narratives (Story A and Story B from the Wechsler Memory Scale). Natural language materials were chosen because they similate experimentally the natural learning situation and permit study of the neural mechanisms by which recall memory becomes more fluid, automatic, or "rote." One week before the PET study, subjects were trained to perfect recall of Story A, while they were exposed to Story B only 60 s prior to PET data acquisition. Despite the substantial differences in level of familiarity (and in free recall performance), patterns of activation were quite similar; activations presumed to reflect recall in both tasks included frontal, inferior temporal, thalamic, anterior cingulate, and cerebellar regions. Many regions were smaller during recall of the familiar story, however, presumably reflecting greater neural efficiency due to practice. In addition, the novel task activated an additional left frontal region that is presumed to reflect more active encoding. The similarity and multiplicity of the activations in the two tasks suggest that the brain uses a multinodal general network for memory tasks such as free recall, while the differences suggest that some nodes in the network may be used for specific components of memory such as encoding and retrieval.

Adult↗
PubMed1995

II. PET studies of memory: novel versus practiced free recall of word lists.

Positron emission tomography (PET) with the tracer H215O was used to measure regional cerebral blood flow in 13 healthy volunteers while they engaged in free recall of 15-item word lists from the Rey Auditory Verbal Learning task. The study was designed so that recall of well-practiced versus novel material could be compared. One week before the PET study, subjects were trained to perfect recall of List A, while they were exposed to list B only 60 s prior to PET data acquisition. As in the companion study of free recall of complex narratives, we observed that practice tended to decrease the size of activations in regions involved in the memory component of the task; we also observed that the novel recall task produced greater activation in left frontal regions, probably due to active encoding. A commonality of other regions observed in this pair of studies, as well as other studies of memory in the literature, suggests that the human brain may contain a distributed multinodal general memory system. Nodes on this network include the frontal, parietal, and temporal cortices, the thalamus, the anterior and posterior cingulate, the precuneus, and the cerebellum. There appears to be a commonality of components across tasks (e.g., retrieval, encoding) that is independent of content, as well as differentiation of some components that may be content-specific or tasks-specific. In addition, these results support a significant role for the cerebellum in cognitive functions such as memory.

Adult↗
PubMed1995

Cranial osteomyelitis: diagnosis and follow-up with In-111 white blood cell and Tc-99m methylene diphosphonate bone SPECT, CT, and MR imaging.

PURPOSE: To assess the usefulness of indium-111 white blood cell and technetium-99m methylene diphosphonate bone single photon emission computed tomography (SPECT), computed tomography (CT), and magnetic resonance (MR) imaging in cranial osteomyelitis. MATERIALS AND METHODS: Twenty-six cases (25 patients: 13 male, 12 female; mean age, 55 years) of suspected osteomyelitis were evaluated. Sixteen were postoperative. Final diagnosis was established by means of bone culture in 18 cases and clinical follow-up in eight. RESULTS: Of 35 CT scans, 10 were true-positive (TP); three false-negative (FN); 13, true-negative (TN); one, false-positive (FP); and eight, equivocal. Of 36 SPECT scans, 19 were TP; 13, TN; one, FP; one, FN; and two, equivocal. Of 11 MR images four were TP; five, TN; and two, FN. CONCLUSION: CT is best for differentiation between soft-tissue and bone infection. MR imaging is best for assessment of the calvaria and skull base. SPECT is best for assessment of altered bone and may be the best technique for follow-up.

Adolescent↗
PubMed1995

Remembering the past: two facets of episodic memory explored with positron emission tomography.

OBJECTIVE: This study used positron emission tomography to examine two kinds of personal memory that are used in psychiatric evaluation: focused episodic memory (recall of past experience, employed in "taking a history") and random episodic memory (uncensored thinking about experience, examined during analytic therapy using free association). For comparison, a third memory task was used to tap impersonal memory that represents general information about the world ("semantic memory"). METHOD: Thirteen subjects were studied using the [15O]H2O method to obtain quantitative measurements of cerebral blood flow. The three conditions were subtracted and their relative relationships examined. RESULTS: The random episodic condition produced activations in widely distributed association cortex (right and left frontal, parietal, angular/supramarginal, and posterior inferior temporal regions). Focused episodic memory engaged a network that included the medial inferior frontal regions, precuneus/retrosplenial cingulate, anterior cingulate, thalamus, and cerebellum. The use of medial frontal regions and the precuneus/retrosplenial cingulate was common to both focused and random episodic memory. The major difference between semantic and episodic memory was activation of Broca's area and the left frontal operculum by semantic memory. CONCLUSIONS: These results indicate that free-ranging mental activity (random episodic memory) produces large activations in association cortex and may reflect both active retrieval of past experiences and planning of future experiences. Focused episodic memory shares some components of this circuit (inferior frontal and precuneus), which may reflect the time-linked components of both aspects of episodic memory, and which permit human beings to experience personal identity, consciousness, and self-awareness.

Adult↗
PubMed1994

Forskolin and methylxanthines block the increase in intracellular pH during meiosis in Xenopus laevis oocytes.

Xenopus oocytes, arrested in late prophase of the meiotic cell cycle, undergo nuclear membrane breakdown (Germinal Vesicle Breakdown, GVBD) in response to progesterone stimulation. During this prophase/M-phase transition the oocytes undergo an increase in their intracellular pH (pHi) from 7.3 to 7.7 in response to the steroid. This increase in pHi appears to be due to the activation of Na+/H+ antiporters in the oocyte plasma membrane. Several studies have shown that the pathway leading to GVBD is blocked by forskolin or methylxanthines which elevate cAMP levels within the oocyte. We have found that these same compounds also blocked the up-regulation of the Na+/H+ exchangers during oocyte meiotic maturation.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Quantification of left ventricular function with an automated border detection system and comparison with radionuclide ventriculography.

Quantification of 2-dimensional echocardiograms with a recently developed automated border detection (ABD) system provides on-line estimation of left ventricular (LV) function. Previous studies showed that short-axis cavity area measurements with the ABD system approximate manually traced cavity areas obtained with conventional 2-dimensional echocardiography. Further clinical validation needs a comparison of LV function between the ABD system and established methods. Fractional area change and ejection fraction measured by the ABD system were compared with ejection fraction measured by radionuclide ventriculography. Echocardiographic measurements were obtained from LV short-axis views at the level of the papillary muscles. Calculation of ejection fraction by the ABD system was based on an algorithm using a modified ellipsoid model. Forty-six patients underwent echocardiography on the same day as radionuclide ventriculography. Patients were included in the study if > or = 75% of the endocardium was visualized with conventional 2-dimensional echocardiography. Twenty-seven of 46 patients (59%) had a technically adequate, conventional echocardiogram. Fractional area change with the ABD system was highly correlated with ejection fraction from radionuclide ventriculography (r = 0.92; SEE 8.4%). Ejection fraction determined by the ABD system and radionuclide ventriculography also showed a strong linear relation in the 23 patients without severe wall motion abnormality (r = 0.90; SEE 9.5%). It is concluded that LV function measurements by the ABD system and radionuclide ventriculography have a strong linear relation.

Adolescent↗