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Biomedical subjects

I Mena

Publications and source records attributed to I Mena.

At least 37 records · Page 2Linked to original sources

Rescue of a synthetic chloramphenicol acetyltransferase RNA into influenza virus-like particles obtained from recombinant plasmids.

We have shown previously that COS-1 cells infected with a vaccinia virus recombinant (vTF7-3) which expresses the T7 RNA polymerase gene and then transfected with four pGEM-derived plasmids encoding the influenza A virus core proteins (nucleoprotein, PB1, PB2, and PA polypeptides) can express a synthetic influenza virus-like chloramphenicol [correction of chloramphenical] acetyltransferase (CAT) RNA (I. Mena, S. de la Luna, C. Albo, J. Martín, A. Nieto, J. Ortín, and A. Portela, J. Gen. Virol. 75:2109-2114, 1994). Here we demonstrate that by supplying the vTF7-3-infected cells with plasmids containing cDNAs of all 10 influenza virus-encoded proteins, the transfected CAT RNA can be expressed and rescued into particles that are budded into the supernatant fluids. The released particles can transfer the enclosed CAT RNA to MDCK cultures and resemble true influenza virions in that they require trypsin treatment to deliver the RNA to fresh cells and are neutralized by a monoclonal antibody specific for the influenza A virus hemagglutinin. Moreover, analysis by electron microscopy showed that the culture medium harvested from the transfected cells contained vesicles that could be labeled with an anti-HA monoclonal antibody and that were similar in size and morphology to authentic influenza virus particles. It is also shown that detection of recombinant particles capable of transmitting the CAT RNA does not require expression of the influenza virus nonstructural protein NS1. All of these data indicate that influenza virus-like particles enclosing a synthetic virus-like RNA can be assembled in cells expressing all viral structural components from recombinant plasmids.

Animals↗

Effect of the ACE inhibitor ceronapril on cerebral blood flow in hypertensive patients.

OBJECTIVE: To assess the effect of the angiotensin-converting enzyme inhibitor ceronapril on cerebral blood flow (CBF) in patients with moderate hypertension. DESIGN: Patients received chlorthalidone 25 mg for 4 weeks, and if diastolic blood pressure remained in the range of 100-115 mm Hg, they were given titrated doses of ceronapril (10-40 mg/d based on blood pressure response) in addition to chlorthalidone for 9 weeks. SETTING: Outpatient research clinic. SUBJECTS: Eligible patients had moderate essential hypertension (diastolic blood pressure 100-115 mm Hg) assessed when the patients were receiving no medications. Thirteen patients were entered into the study; 1 withdrew for reasons unrelated to the study drug. Twelve patients (11 men, 1 woman; mean age 52 y) completed the study. INTERVENTION: Ceronapril, given with chlorthalidone. MAIN OUTCOME MEASURES: CBF measurements were taken at the start and end of ceronapril therapy using intravenous 133Xe; blood pressures were determined weekly. RESULTS: Mean arterial blood pressure decreased from 130 +/- 4 to 120 +/- 7 mm Hg after 4 weeks of chlorthalidone administration, and fell further to 108 +/- 8 mm Hg after an additional 9 weeks of combined chlorthalidone-ceronapril therapy (p < 0.05). CBF fell from 44 +/- 15 to 34 +/- 5 mL/min/100 g during the 9 weeks of combined therapy (p = 0.05). No adverse effects consistent with decreased CBF were observed. The decrease in CBF was not linearly correlated with the change in systemic blood pressure, but was strongly correlated (r = -0.937; p < 0.001) with the initial CBF. CONCLUSIONS: The decrease in mean arterial blood pressure was not associated with a decrease in CBF. Patients with high CBF may be predisposed to a decrease in CBF when treated with ceronapril and chlorthalidone.

Aged↗

Neural basis of confabulation.

We present a case of acute alcohol-induced Korsakoff amnesia. A severe amnestic-confabulatory syndrome characterized the early clinical status. The initial neuropsychological tests demonstrated severe learning deficits plus impaired performance on many, but not all, tests of frontal lobe function. Single-photon emission CT (SPECT) at this stage showed hypoperfusion in the orbital and medical frontal regions and the medial diencephalic area. Four months later, the patient's amnesia remained but there was no confabulation. Repeat neuropsychological tests confirmed an ongoing severe amnesia, but performance on the frontal lobe tests now was normal. Repeat SPECT showed a return to normal perfusion in the frontal brain areas but little improvement in the medial diencephalic region. These findings along with data from the clinical literature suggest that confabulation results from dysfunction of orbital and a medial frontal cortex.

Adult↗

Regional 133xenon cerebral blood flow and cerebral 99mTc-HMPAO uptake in patients with obsessive-compulsive disorder before and during treatment.

We previously reported increased regional cerebral cortical uptake and decreased caudate nucleus uptake of 99mTc-HMPAO in patients with obsessive-compulsive disorder(OCD) before treatment compared to matched normal controls. In the present study, we determined whether or not these changes persisted during treatment. Single-photon emission computed tomography was used to measure regional cerebral blood flow (rCBF) by 133Xe inhalation and cerebral uptake of 99mTc-HMPAO in eight adult male OCD patients before and during treatment with chlomipramine, and in eight age-matched normal male controls. With 133Xe, there were no significant differences in rCBF between patients with OCD and their matched controls, and no significant differences in rCBF in the patients before and during treatment. Significantly increased HMPAO uptake in the orbital frontal cortex, posterofrontal cortex, and high dorsal parietal cortex bilaterally occurred in the OCD patients before treatment compared to their matched controls, and there were significant reductions of HMPAO uptake, into the normal range, in all these areas in the patients during treatment. Significantly reduced HMPAO uptake in the caudate nucleus bilaterally occurred in the patients before treatment compared to their matched controls, and these reductions persisted during treatment. This study provides additional support for the involvement of both the orbital frontal cortex and the caudate nuclei in the pathophysiology of OCD.

Adult↗

Neural-network-based classification of cognitively normal, demented, Alzheimer disease and vascular dementia from single photon emission with computed tomography image data from brain.

Single photon emission with computed tomography (SPECT) hexamethylphenylethyleneamineoxime technetium-99 images were analyzed by an optimal interpolative neural network (OINN) algorithm to determine whether the network could discriminate among clinically diagnosed groups of elderly normal, Alzheimer disease (AD), and vascular dementia (VD) subjects. After initial image preprocessing and registration, image features were obtained that were representative of the mean regional tissue uptake. These features were extracted from a given image by averaging the intensities over various regions defined by suitable masks. After training, the network classified independent trials of patients whose clinical diagnoses conformed to published criteria for probable AD or probable/possible VD. For the SPECT data used in the current tests, the OINN agreement was 80 and 86% for probable AD and probable/possible VD, respectively. These results suggest that artificial neural network methods offer potential in diagnoses from brain images and possibly in other areas of scientific research where complex patterns of data may have scientifically meaningful groupings that are not easily identifiable by the researcher.

Aged↗

Investigation of abnormal appearing thyroid glands on Tc-99m sestamibi breast scintimammography.

Of 507 breast scintimammograms performed using Tc-99m sestamibi, 34 patients were incidentally found to have abnormal appearing thyroid glands. The authors sought to investigate the clinical significance and/or ascertain an extraneous causative factor for these findings. One cold thyroid nodule was detected and was proven benign through biopsy. Two cases of subacute and chronic thyroiditis were proven, and it is possible that additional patients had this disease process. Focal areas of increased thyroid Tc-99m sestamibi uptake were observed in eight patients and probably represent parathyroid adenomas, nonautonomous hyperfunctioning thyroid nodules, or nontoxic multinodular goiter. The results did not yield an extraneous causative factor, underlying pathology, or clinically significant disease in all of the patients investigated, but the findings suggest a need for careful evaluation of any unusual uptake in the thyroid gland and the rest of the image. The authors do not recommend investigation of all abnormal appearing thyroid glands on Tc-99m sestamibi scintimammography. However, clinical correlation should be recommended.

Adult↗

SPECT in dementia: clinical and pathological correlation.

BACKGROUND: The clinical diagnosis of dementia continues to be flawed. Although the diagnosis of Alzheimer's disease (AD) is better than 90% at research centers in highly selected patients, the diagnosis of patients with non-AD dementias and atypical AD patients is poor. Single photon emission computed tomography (SPECT) is a functional imaging technique touted as a diagnostic technique for the degenerative disorders. However there have been few clinicopathological studies using SPECT. METHODS: Twenty-seven consecutive dementia patients were evaluated clinically at a University-based specialty dementia clinic, and a diagnosis of a specific dementia was made. SPECT imaging was used in helping to select a clinical diagnosis. The correlations between clinical, SPECT and autopsy diagnoses were analyzed. RESULTS: Single photon emission computed tomography predicted pathologic diagnosis in 25 of 27 patients with dementia (92.6%), compared with clinical diagnosis, which was confirmed in 20/27 (74.1%). Distinct patterns were associated with dementia caused by AD, Fronto-Temporal Dementia (FTD), and Jakob-Creutzfeldt Disease (JCD). Vascular insults not seen with computerized tomography (CT) or magnetic resonance imaging (MRI) were found with SPECT. Three different pathologies were found in patients with Parkinsonian-Dementias (PD): Lewy-Body Variant of AD, Diffuse Lewy-bodies without plaques, and substantia nigra neuronal loss without plaques or Lewy-bodies. All showed a temporal-parietal pattern with SPECT that was similar to AD. CONCLUSION: SPECT provides useful positive information in dementia, particularly the differentiation of AD, FTD, and JCD. However, it does not distinguish PD from AD.

Adult↗

111-indium-DTPA-IgG lung imaging in patients with pulmonary and HIV infection.

111-Indium-DTPA-IgG (111In-IgG) is a new radiopharmaceutical that has been evaluated for the detection of infection without the need for in vitro cell labeling. We prospectively studied this agent in 33 patients suspected of having lung infections, most of whom also had HIV infection, and three patients with HIV infection and diarrhea without lung disease. Anterior and posterior lung images in the upright position were obtained within 24 h after intravenous administration of 2 mCi of 111In-IgG and were read in a blinded fashion by two nuclear medicine physicians. Of 29 patients suspected to have Pneumocystis carinii pneumonia (PCP), the diagnosis was confirmed by bronchoalveolar lavage in 18. Diffusely increased lung uptake of 111In-IgG was found in 17 of 18 patients who had PCP and was normal in 10 of 11 patients without PCP. The intensity of 111In-IgG uptake was related to sever gas exchange abnormality. Two patients with apparent bacterial lung infections had focal accumulation of 111In-IgG while two patients with minor radiographic abnormalities had no increased uptake. Normal lung uptake also occurred in two of three HIV-positive patients who had diarrhea and no lung disease. 111In-IgG appears to be useful in the detection of PCP and other pulmonary infections.

AIDS-Related Opportunistic Infections↗

Technetium-99m-sestamibi scintimammography of breast lesions: clinical and pathological follow-up.

UNLABELLED: Mammography and physical examination combined have a sensitivity of 85% for the detection of breast carcinoma. Mammography also has a positive predictive value of 15%-30%. The aim of this study was to evaluate the usefulness of scintimammography using 99mTc-sestamibi as a complementary technique to mammography for the detection of breast carcinoma to improve mammography's sensitivity and specificity. METHODS: We studied 100 consecutive patients (mean age 48.3 +/- 10.8 yr) who had 106 lesions warranting biopsy (67 lesions) or fine needle aspiration cytology (FNA) (39 lesions) of the breast. There were 85 palpable and 21 nonpalpable lesions. The size of the lesions on the mammograms were moderate (2.3 +/- 1.8 x 1.9 +/- 1.5 cm). Each patient received 20 mCi 99mTc-sestamibi intravenously. Five and 60 min postinjection, planar breast images in the lateral prone position were obtained. An anterior erect projection was then obtained to visualize the axilla and, if needed, a posterior oblique prone projection. RESULTS: Scintimammography was true-positive in 30 lesions with biopsy-confirmed breast carcinoma; it was true-negative in 65 lesions subsequently proved to be benign. There were nine breast lesions with benign findings in which the scintimammography result was positive (false-positive scintimammography) for cancer. Finally, two lesions with pathologically proven carcinomas demonstrated a negative scintimammographic result. Therefore, in this group, the sensitivity of scintimammography was 93.7% with a specificity of 87.8%; the positive predictive value was 76.9%. The negative predictive value was 97%. CONCLUSION: Scintimammography is a highly sensitive test that improves the specificity of conventional mammography for the detection of breast carcinoma.

Biopsy, Needle↗

Reduction of cerebral blood flow in older depressed patients.

BACKGROUND: We investigated regional cerebral blood flow in older, drug-free depressed patients and examined factors that might be related to rCBF. METHODS: We studied 39 physically healthy depressed patients over the age of 50 years and 20 psychiatrically healthy control subjects. Regional cerebral blood flow was measured with single photon emission computed tomography, using both xenon 133 (to quantify regional cerebral blood flow) and 99mTc-hexamethylpropylene amine oxime (to make regional comparisons). From magnetic resonance imaging, we derived a semiquantitative measure of areas of white matter hyperintensity and a ventricle-to-brain ratio. RESULTS: Patients exhibited a global reduction in regional cerebral blood flow compared with controls, with the orbital frontal and inferior temporal areas affected bilaterally. Regional cerebral blood flow was also reduced in higher brain slices in the right but not the left hemisphere. Significant predictors of lowered regional cerebral blood flow were being depressed, being male, and having a greater ventricle-to-brain ratio. There appeared to be a subgroup of patients who demonstrated large areas of white matter hyperintensity and low regional cerebral blood flow. CONCLUSIONS: Cerebral blood flow was lower in older, medication-free depressed patients than in age-matched control subjects, involved the orbital frontal and anterior temporal regions, and was more reduced in the right hemisphere.

Age Factors↗

Review of imaging techniques for the diagnosis of breast cancer: a new role of prone scintimammography using technetium-99m sestamibi.

Imaging techniques currently used for the diagnosis of breast cancer are reviewed and compared. Besides mammography, magnetic resonance imaging, positron emission tomography, and thallium-201 scintimammography, a new role of technetium-99m sestamibi scintimammography is discussed. It is concluded that while mammography remains the procedure of choice in screening asymptomatic women for breast cancer, other imaging methods play an important role in detecting malignancies in symptomatic patients. 99mTc-sestamibi scintimammography has high sensitivity and improves the specificity of conventional mammography for the detection of breast cancer; with this technique, prone imaging is preferable to supine imaging. 99mTc-sestamibi scintimammography thus deserves further study as a screening technique.

Adult↗

Assessment of cerebral perfusion using quantitative EEG cordance.

Brain electrical activity is related to cerebral perfusion. The nature of this relationship is unclear, however, and surface-recorded activity has not been a reliable indicator of brain perfusion. We studied 27 subjects, all of whom were examined with single photon emission tomography (SPECT) and quantitative electroencephalography (QEEG), to assess associations between QEEG cordance and relative brain perfusion. Cordance has two indicator states: concordance, which may indicate high perfusion; and discordance, which may indicate low perfusion. We used multiple linear regression to assess the association between cordance and SPECT values, and found that cordance values were strongly associated with tissue perfusion. Concordance in the alpha band was associated both with mean tissue perfusion and the volume of normally perfused tissue, and it had a stronger association with perfusion than any other QEEG variable. Discordance in the beta 1 band was associated with mean perfusion, and it had a stronger association than did relative but not absolute power. These data suggest that cordance may be useful for the noninvasive assessment of brain perfusion.

Adult↗

Synthesis of biologically active influenza virus core proteins using a vaccinia virus-T7 RNA polymerase expression system.

An in vivo system in which expression of a synthetic influenza virus-like chloramphenicol acetyltransferase (CAT) RNA is driven by influenza virus proteins synthesized from cloned cDNAs has been developed. Expression of the four influenza virus core proteins (nucleoprotein, PA, PB1 and PB2) was performed by transfection of four pGEM recombinant plasmids, each containing one of the four viral genes, into cell cultures previously infected with a vaccinia virus recombinant encoding the T7 RNA polymerase (vTF7-3). When a naked negative-sense influenza virus-like CAT RNA was transfected into cells expressing the four influenza virus proteins, CAT activity was detected in the cell extracts, demonstrating that the expressed proteins had RNA-synthesizing activity. In this system, CAT RNA templates containing additional nucleotides at the 3' end were also expressed, resulting in CAT activity. This showed that the influenza virus polymerase can recognize its promoter when located internally on an RNA template. In influenza virus-infected cells however, CAT activity was detected only when the CAT RNA contained the viral promoter at the exact 3' end and was transfected as in vitro assembled ribonucleoprotein. These results are discussed in terms of the different requirements of the two helper systems for expression of an exogenously added RNA.

Animals↗

Agenesis of corpus callosum and dementia of the Alzheimer's type: a review and case report.

This paper describes a previously sufficiently functioning 57 year old man who presented with a recent onset of frontal behaviour. Partial agenesis of corpus callosum was an incidental finding on a computerized tomography scan. The EEG was within normal limits and neuropsychological testing did not reveal any interhemispheric disconnection. A SPECT-Scan revealed bilateral hypoperfusion, consistent with Alzheimer's dementia. Normal functioning up to 50 years of age and a later manifestation of Alzheimer's disease along with agenesis of carpus callosum is of clinical interest as such an association has not been published.

Agenesis of Corpus Callosum↗

Cerebral blood flow changes with acute cocaine intoxication: clinical correlations with SPECT, CT, and MRI.

In summary, these data suggest that widespread primary or secondary cerebral vasoconstriction is common in patients with neurological complications from cocaine. In most patients, SPECT showed wide-spread hypoperfusion in regions that had no clear clinical significance (e.g., the periventricular area). In many, the SPECT was performed more than 24 hours after the onset of neurological symptomatology. These findings raise several questions. It has been assumed that these SPECT changes in patients with acute neurological symptoms are temporary, although it will be important to determine whether these areas of hypoperfusion persist after symptoms have abated. Recently, Holman and colleagues (1991) found multifocal and deep areas of hypoperfusion with SPECT in 16 of 18 patients with a history of chronic cocaine abuse. Although most of the subjects tested positive for cocaine, several had abstained from cocaine use for weeks prior to the study. All 18 subjects had neuropsychological deficits, 13 mild and 5 moderate. Similarly, Pascual-Leone and colleagues (1991) have shown that CT scan atrophy strongly correlates with the duration of cocaine abuse, suggesting that brain injury may occur with continued use of cocaine. It is the authors' concern that cocaine abuse might produce permanent changes in cerebral perfusion. In conclusion, brain SPECT was found to be a useful procedure in the evaluation of acute cocaine intoxication. Brain SPECT revealed focal cortical lesions not seen on head CT or MRI, which corresponded to clinical deficits. In addition, [99mTc]HMPAO brain SPECT had a characteristic scalloped appearance, and this may be a marker for acute intoxication with cocaine. This study further supports the contention that cocaine causes neurological disease by its vasoconstrictive action.

Adult↗

Prone scintimammography in patients with suspicion of carcinoma of the breast.

Mammography and physical examination have a sensitivity of 85 percent for detection of carcinoma of the breast. Mammography also has a positive predictive value of 15 to 30 percent. The aim of this study was to evaluate the usefulness of scintimammography (SMM) as a screening technique for the detection of carcinoma of the breast and compare the test's sensitivity and specificity with that of mammography. We conducted SMM on 59 female patients in whom abnormal mammogram and physical examination warranted biopsy of the breast or fine needle aspiration cytology of the breast, or both. Each patient received 20 millicuries of 99mTc Sestamibi intravenously. Five and sixty minutes postinjection, planar breast images in lateral and posterior oblique views were obtained. In 23 patients with biopsy-confirmed carcinoma of the breast, the SMM result was positive. In 33 patients with benign breast lesions, no increased uptake of Sestamibi was noted in the breast. Five other patients with benign lesions of the breast had false-positive scans. There was one patient with an intraductal carcinoma and a cluster of microcalcifications on mammography without an associated mass, for whom the 99mTc Sestamibi scan was negative. In the group of patients studied, the sensitivity of SMM was 95.8 percent, specificity was 86.8 percent, positive predictive value was 82.1 percent and, most importantly, the negative predictive value for the detection of carcinoma of the breast was 97.1 percent. We conclude in this pilot study that SMM is a highly sensitive test that improves the specificity of conventional mammography for the detection of carcinoma of the breast and deserves further study as a screening technique to potentially reduce the number of mammographically "indicated" biopsies of the breast that yield negative results for carcinoma.

Adult↗

Cerebral abnormalities in myotonic dystrophy. Cerebral blood flow, magnetic resonance imaging, and neuropsychological tests.

OBJECTIVE: To study cerebral abnormalities in myotonic dystrophy (MD) and determine the different patterns of cerebral function in patients with MD with maternal (mMD) vs paternal (pMD) inheritance. DESIGN: Patients with MD and normal controls were studied with neuropsychological testing, magnetic resonance imaging, and single photon emission computed tomography. SETTING: Studies were done at Harbor-UCLA Medical Center, Torrance, Calif. PATIENTS AND OTHER PARTICIPANTS: Twenty-two consecutive-patients with MD, 11 of whom had pMD and eight mMD, and 10 normal controls were studied. Diagnoses were made on the basis of family history, electromyography, and clinical examinations. Normal subjects in the same age distribution were studied for comparisons. RESULTS: We found significantly lower neuropsychological performance and cerebral blood flow in the patients with MD compared with the controls. Patients with mMD had statistically lower scores on IQ tests and more extensive cerebral hypoperfusion when compared with those with pMD. Changes in cerebral blood flow were most severe in the frontal and temporoparietal association cortex. Cerebral blood blow measures strongly correlated with IQ. CONCLUSIONS: Patients with mMD had earlier onset of disease and lower IQs than the pMD group. The pattern of cerebral perfusion in the mMD group was consistent with a diffuse brain injury, while cerebral perfusion in pMD showed more minor changes. These findings emphasize the cognitive differences between mMD and pMD.

Adolescent↗