Biomedical subjects

R Lambert

Publications and source records attributed to R Lambert.

At least 19 recordsLinked to original sources

PubMed1992

Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site.

The three-domain structure of porphobilinogen deaminase, a key enzyme in the biosynthetic pathway of tetrapyrroles, has been defined by X-ray analysis at 1.9 A resolution. Two of the domains structurally resemble the transferrins and periplasmic binding proteins. The dipyrromethane cofactor is covalently linked to domain 3 but is bound by extensive salt-bridges and hydrogen-bonds within the cleft between domains 1 and 2, at a position corresponding to the binding sites for small-molecule ligands in the analogous proteins. The X-ray structure and results from site-directed mutagenesis provide evidence for a single catalytic site. Interdomain flexibility may aid elongation of the polypyrrole product in the active-site cleft of the enzyme.

Binding Sites↗

PubMed1992

Crystallization and preliminary X-ray investigation of Escherichia coli porphobilinogen deaminase.

Porphobilinogen deaminase, the polymerase that catalyses the synthesis of preuroporphyrinogen, the linear tetrapyrrole precursor of uroporphyrinogen III, has been crystallized from sodium acetate buffer with polyethylene glycol 6000 as precipitant. The crystals are orthorhombic and the space group is P2(1)2(1)2, with unit cell dimensions a = 88.01 A, b = 75.86 A, c = 50.53 A and alpha = beta = gamma = 90 degrees, indicating a single molecule of 34 kDa in the asymmetric unit. The crystals grow to dimensions of 1 mm x 2 mm x 0.5 mm within two weeks in the dark and are stable in the X-ray beam for at least 40 hours. Diffraction data beyond 1.7 A resolution, observed with a synchrotron radiation source, indicate that a high resolution structure analysis is feasible.

Crystallization↗

PubMed1992

Comparison between technetium-99m-teboroxime and thallium-201 dipyridamole planar myocardial perfusion imaging in detection of coronary artery disease.

Technetium-99m (TC-99m)-teboroxime is a new myocardial perfusion imaging agent. The purpose of this prospective study was to compare Tc-99m-teboroxime with thallium-201 imaging after the administration of dipyridamole. Thirty patients referred for the evaluation of chest pain were studied with both thallium-201 and Tc-99m-teboroxime dipyridamole scans (mean interval 2 days). Dipyridamole was administered at 0.142 mg/kg/min for 4 minutes. Planar imaging (3 standard views) was obtained at 5 and 240 minutes after the injection of 2.2 mCi of thallium-201. Tc-99m-teboroxime (18 to 25 mCi) was injected after dipyridamole infusion. A second injection, at rest, was repeated 4 hours later. Planar imaging (3 standard views of 1 minute/view for the first 2 views, and 90 seconds for the last view) was obtained 2 minutes after Tc-99m-teboroxime injection. Blinded reading was performed by 3 observers. Thallium-201 showed perfusion defects in 182 myocardial segments corresponding to 33 of 45 (73%) significantly stenosed coronary arteries (greater than or equal to 70% reduction in endoluminal diameter), and Tc-99m-teboroxime detected 160 abnormal segments corresponding to 29 of 45 (64%) stenosed arteries. Thallium-201 and Tc-99m-teboroxime studies were normal in 3 patients. In conclusion, this study shows that there is a good correlation in the imaging results found with thallium-201 and Tc-99m-teboroxime using dipyridamole infusion on both a segmental and a diagnostic comparison.

Adult↗

PubMed1992

Curative non-surgical combined treatment of squamous cell carcinoma of the oesophagus.

Between April 1982 and June 1989, 65 patients (15 T1, 13 T2, 32 T3, 5 T4) with squamous cell carcinoma of the oesophagus were treated with a curative intent with multimodality combined treatment. A first course of 5-fluorouracil and cisplatin was given during work up, especially if NdYAG laser therapy was used. Irradiation was started 3-4 weeks after induction and two courses of concomitant chemotherapy were given during the radio therapy (aiming at 64 Gy over 7 weeks). Actuarial survival was 79.6% at 1, 36.7% at 3 and 26.7% at 5 years. 5 year survival rates were 56.3% for T1, 29.8% for T2 and 12.9% for T3. All T4 cases died within 16 months. Complete initial disease response was achieved in 76%. Tolerance was good. Thus patients with squamous cell carcinoma of the oesophagus can have long survival and may be cured with combined modality therapy. This treatment may be an alternative to radical surgery when there is a high risk of operative mortality.

Adult↗

PubMed1992

Endosonography-guided treatment of esophageal carcinoma.

Endosonography is helpful in managing patients with esophageal cancer due to its capacity to stage the tumor for the depth of tumoral invasion and the presence of metastatic lymph nodes. Thus, ES will help the surgeon to determine if surgery is advisable. If the patient does not undergo surgery, it will provide a very accurate prognosis and allow the adaptation of non-surgical multimodal therapy to determine tumor extension. Finally, following the initial phase of treatment. ES will be useful in the follow-up, especially to detect and stage recurrences.

Actuarial Analysis↗

PubMed1992

In vivo measurement of atrial natriuretic peptide receptors using nuclear imaging.

We have successfully visualized atrial natriuretic peptide (ANP) receptors in vivo using nuclear imaging. 123I-Labelled ANP, injected in green vervet monkeys, was rapidly bound to ANP receptors in the kidneys and lungs. That the observed uptake was receptor mediated was demonstrated with competition studies using simultaneous injection of unlabelled ANP 99-126. It was possible to distinguish between the ANP receptor subtypes by the use of selective antagonists. Thus coinjection of ANP 102-121-des[Gln, Ser, Gly, Leu, Gly] (C-ANP), an ANP analog that selectively binds to the ANP C-receptor, decreased uptake in the kidneys by 50% but increased relative uptake in the lungs and soft tissues. This method permits for the first time, the dynamic in vivo analysis of ANP receptors and their interaction with endogenous ligand. Differences and changes in local ANP receptor concentrations and occupancy could be detected. Since ANP receptor density and affinity are influenced by various physiological and pathological conditions, clinical and diagnostic applications seem possible.

Animals↗

PubMed1992

Psychiatric and family functioning in children with leukemia and their parents.

The present study reports data from a cross-sectional investigation of the psychiatric and psychosocial functioning of 55 children diagnosed with acute lymphocytic leukemia and their families at three points in time: diagnosis (newly diagnosed), 1 year postdiagnosis, and 1 year after the completion of chemotherapy (off-therapy). Results reveal minimal psychopathology in these children and their parents based on self- and informant-reports and structured diagnostic interviews. These families appear to be functioning adequately and report more family cohesiveness and marital satisfaction after chemotherapy was completed. Coping strategies commonly used by children and their parents include problem-solving, a positive outlook, and good communication. Implications for psychiatric consultation are presented.

Adaptation, Psychological↗

PubMed1992

Detection and localization of parathyroid adenomas in patients with hyperparathyroidism using a single radionuclide imaging procedure with technetium-99m-sestamibi (double-phase study)

Dual radionuclide imaging using a combination of 201Tl with either 99mTcO4- or 123I is recognized as a useful procedure in the preoperative localization of parathyroid adenomas. Recently, 99mTc-sestamibi (MIBI) has been introduced for myocardial perfusion imaging as an alternative to 201Tl. The purpose of this prospective study was to evaluate parathyroid scan using early and late imaging following MIBI injection. Twenty-three patients (21 F, 2 M, mean age: 57 yr) with a clinical and biologic diagnosis of hyperparathyroidism were submitted to a MIBI study prior to surgical exploration of the neck. Cervico-thoracic planar imaging (anterior view, 10 min/view) was performed at 15 min and at 2-3 hr after an intravenous injection of 20-25 mCi of MIBI. A positive MIBI scan for parathyroid adenoma was defined as an area of increased focal uptake which persisted on late imaging, contrary to the uptake in the normal thyroid tissue which progressively decreases over time (differential washout). Surgical exploration of the neck, performed between 1 day and 72 days (average: 16 days) after the MIBI study, showed a parathyroid adenoma in 21 patients and hyperplasia in two patients. MIBI scan correctly detected and localized 19/21 adenomas (90%). In conclusion, parathyroid imaging using a single radionuclide with MIBI (early and late study with differential washout analysis) is a promising procedure in the preoperative detection and localization of parathyroid adenomas in patients with primary hyperparathyroidism.

Adenoma↗

PubMed1992

Differentiation of side chain isomers of ring-substituted amphetamines using gas chromatography/infrared/mass spectrometry (GC/IR/MS).

Common analytical methods used for identifying samples obtained from clandestine laboratories were evaluated for their ability to differentiate between possible amphetamine isomers and homologs. A series of ring-substituted (4-methyl, 4-methoxy, and 3,4-methylenedioxy) amphetamine and N-methylphenethylamine isomers was analyzed using color tests, thin-layer chromatography, gas chromatography/mass spectrometry (GC/MS) and GC/infrared (GC/IR). The N-acetyl derivatives of the isomers were analyzed using GC/IR/MS. GC/IR/MS readily differentiated the 4-methylphenylalkylamine isomers. MS and IR spectra were also obtained for each pair of the 4-methoxyphenylalkylamine isomers and the 3,4-methylenedioxyphenylalkylamine isomers, but differentiation via GC/IR/MS was difficult. The N-acetyl derivatives of each pair of isomers could be readily differentiated using GC/IR/MS. Good library researchable spectra for N-acetylamphetamine could be obtained for IR identification with 10 ng (on-column) and MS identification with 2 ng. The spectrometrically independent IR and MS data obtained for the N-acetyl derivatives indicated that the combination of GC/IR/MS can add a significant level of confidence in the analysis of ring-substituted arylalkylamines.

Amphetamines↗

PubMed1992

Comparison between thallium-201, technetium-99m-sestamibi and technetium-99m-teboroxime planar myocardial perfusion imaging in detection of coronary artery disease.

Technetium-99m-sestamibi (MIBI) and 99mTc-teboroxime (TEBO) are two new myocardial perfusion imaging agents. The purpose of this prospective study was to compare MIBI and TEBO to 201TI planar imaging. Eighteen patients with significant coronary artery disease on coronary angiogram were submitted to three treadmill stress tests performed within 3 mo and were imaged with the three radiopharmaceuticals as follows. 1. TI: 2.2 mCi, immediate and delayed views (4 hr later, 8 min/view). 2. TEBO: 15-20 mCi at stress (1 min/view) and a second injection was repeated 4 hr later at rest (20-25 mCi). 3. MIBI: 15-18 mCi at stress (8 min/view) and 1-4 days later, 15-18 mCi at rest. Patients achieved similar levels of exercise. A blinded reading was performed by three observers. The left ventricle was divided into three segments/view and ischemic/normal wall ratios were also determined. Segmental comparison showed an agreement in 85% (138/162) of the segments between TI and TEBO, in 92% (149/162) between TI and MIBI and in 84% (136/162) between MIBI and TEBO. Abnormal TI, MIBI and TEBO studies were seen in 16 (89%), 16 (89%) and 15 (83%) patients, respectively, detecting 77, 75 and 65 abnormal segments. Ischemic-to-normal wall ratios were 0.75 +/- 0.06, 0.73 +/- 0.08 and 0.78 +/- 0.08 for TI, MIBI and TEBO, respectively. In conclusion, although the biologic characteristics of these agents are different, this study showed a good correlation between them in detection of significant coronary artery disease (high pretest likelihood population).

Aged↗

PubMed1991

Karyotypic evolution in B-cell chronic lymphocytic leukaemia.

Sequential cytogenetic studies were performed on a minimum of two and a maximum of nine occasions (mean 3.6) on the peripheral blood leucocytes of 112 patients with B-CLL. On initial cytogenetic analysis, 58 had a normal karyotype and 64 had a clonal abnormality. Karyotypic evolution occurred in 18 patients (16%). There was no significant difference in the incidence of disease progression between patients with a stable karyotype and those who underwent karyotypic evolution. In only one patient was there a clear association between disease progression, a change in cell morphology and karyotypic evolution.

Clone Cells↗

PubMed1991

Technetium 99m SESTAMIBI myocardial perfusion imaging: comparison between treadmill, dipyridamole and trans-oesophageal atrial pacing "stress" tests in normal subjects.

The purpose of this study was to determine the blood clearance, myocardial uptake and heart/lung and heart/liver ratios of technetium 99m methoxyisobutylisonitrile (99mTc-SESTAMIBI) following 3 different types of cardiac stimulation in normal subjects: treadmill stress (STRESS), intravenous administration of dipyridamole (DIP) and trans-oesophageal atrial pacing (TAP). Ten normal volunteers were submitted to 3 injections of 99mTc-SESTAMIBI (10 mCi/70 kg, separated by an interval of 7 days) following STRESS (standard Bruce protocol), DIP (0.142 mg/kg.min during 4 min) and TAP procedures. Blood samples were collected from 1 to 60 min after each 99mTc-SESTAMIBI injection. Planar imaging was performed at 5, 30 and 60 min. Blood retention (percentage of injected dose at 1 min) was 56% +/- 4%, 24% +/- 4% and 38% +/- 6% for STRESS, DIP and TAP, respectively (P less than 0.001). Myocardial uptake was similar for the 3 procedures while the heart lung ratio at 60 min was 3.1 +/- 0.5, 3.8 +/- 0.6 and 3.2 +/- 0.5 for STRESS, DIP and TAP, respectively. Heart/liver ratio at 60 min was 1.9 +/- 0.5, 1.3 +/- 0.3 and 1.1 +/- 0.2 for STRESS, DIP and TAP, respectively (P less than 0.001). These results demonstrated that the 3 types of cardiac stimulation show good imaging parameters with 99mTc-SESTA-MIBI.

Adult↗

PubMed1991

Single-dose pharmacokinetics of 14C-lovastatin in chronic renal failure.

An open study on the pharmacokinetics of lovastatin was conducted in six patients with chronic renal failure (mean creatinine clearance, 0.40 ml/sec; range, 0.20 to 0.65 ml/sec) and seven healthy subjects. Plasma levels of 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitory activity (total and active) and total radioactivity were determined over 168 hours after a single dose of 80 mg 14C-lovastatin. The mean area under the plasma concentration-time curve for active inhibitors were 606 +/- 346 and 282 +/- 138 ngEq.hr/ml (p = 0.04) in patients and control subjects, respectively. Total inhibitors in plasma and total radioactivity were similarly elevated in patients with chronic renal failure. Results indicate that patients with severe renal dysfunction have altered elimination kinetics of lovastatin. Current ongoing clinical studies in patients with renal dysfunction will allow better assessment of the pharmacodynamic meaning of our observations.

Adult↗

PubMed1991

Single photon emission computed tomography (SPECT) in cerebellar disease: cerebello-cerebral diaschisis.

Single photon emission computed tomography assessments were conducted in normal controls (n = 25), patients with unilateral cerebellar infarctions (n = 4), patients with olivopontocerebellar atrophy (OPCA; n = 15) and patients with Friedreich's ataxia (FA; n = 6). In subjects with unilateral cerebellar infarctions, crossed cerebellar-cortical diaschisis was observed: reduced cerebellar hexamethylpropyleneamine oxime (HMPAO) uptake was invariably accompanied by a diminution of HMPAO in the contralateral basal ganglia and frontoparietal cortex. OPCA and FA patients had various degrees of decreased HMPAO uptake in both the cerebellum and cerebral hemispheres.

Adult↗

PubMed1991

Delayed diagnosis of infantile meningitis. Medical and legal outcomes.

While the diagnosis of meningitis in the infant can be difficult due to the lack of definitive signs, a delay in the diagnosis can markedly increase morbidity and mortality. Eighteen cases of meningitis that were reported to a malpractice carrier over 75 months were evaluated for medical and legal outcome. Fourteen had a delay in diagnosis that was judged to have occurred due to substandard care. All had a poor outcome; one half died and the other half had neurologic complications. Four cases resulted in payment to the patient. Median payment was $1,100,000. When care was standard, no payment or legal action occurred.

Chi-Square Distribution↗

PubMed1991

Technetium-99m-sestamibi myocardial perfusion imaging in detection of coronary artery disease: comparison between initial (1-hour) and delayed (3-hour) postexercise images.

Technetium-99m-sestamibi, a new myocardial perfusion imaging agent, does not show significant or rapid myocardial redistribution following its intravenous injection at stress. The purpose of this study was to evaluate the myocardial clearance of 99mTc-sestamibi and ischemic/normal wall ratios at 1 hr and at 3 hr after injection at stress in patients with significant coronary artery disease. Twenty-five patients with ischemic defects on 201Tl scans (n = 15) and/or significant disease on coronary angiogram (n = 18) were prospectively studied. Planar images were obtained at 65 and at 190 min after an injection at stress of 20-25 mCi of 99mTc-sestamibi. A rest study was performed 1-6 days later. Ischemic/normal wall ratios were 0.73 +/- 0.10 and 0.83 +/- 0.12 (p less than 0.05) at 1 and 3 hr, respectively (0.98 +/- 0.15 at rest). Myocardial washout was 26% +/- 12% for normal walls and 15% +/- 8% for ischemic walls (p less than 0.001). Segmental analysis showed 48 and 46 ischemic segments at 1 and 3 hr, respectively. In conclusion, although only a few ischemic segments were missed at 3 hr, significantly lower ischemic/normal wall ratios were found at 1 hr. Faster myocardial washout from normal walls is responsible for the partial reduction of this ratio.

Coronary Disease↗

PubMed1990

Pediatric cerebrovascular disease. Alterations of regional cerebral blood flow detected by TC 99m-HMPAO SPECT.

Regional cerebral blood flow (rCBF) alterations, as determined by single photon emission computed tomography (SPECT) using technetium Tc 99m hexamethyl propylenamine oxime (Tc 99m-HM-PAO), were studied in 15 infants and children presenting with cerebrovascular disorders between the ages of 2 weeks and 16 years. The rCBF patterns were correlated with clinical presentation, electroencephalographic patterns, radiologic studies, including computed tomography and magnetic resonance imaging of the head, and cerebral angiography. All patients presented with motor weakness that was accompanied in some with dysphasia, defects in visual fields, obtundation, seizures, and high temperature. Perturbations of rCBF with Tc 99m-HMPAO SPECT brain scanning were detected in all patients investigated, with no adverse effects related to the radiotracer. All patients had a focal area of decreased rCBF, with adjacent hyperemia in 3 patients. In 7 patients, there was an rCBF decrease in a vascular distribution, mainly that of the middle cerebral artery, that correlated with the clinical findings and a focal electroencephalogram, as well as computed tomography and magnetic resonance imaging of the head. Impairment of rCBF was more extensive in 3 children, while early abnormal SPECT findings preceded abnormal computed tomographic findings in another 2 children. In 2 patients, Tc 99m-HMPAO SPECT was the only positive radiologic test to correlate with focal clinical and electroencephalographic abnormalities, in view of repeated normal computed tomographic scans. We conclude that Tc 99m-HMPAO SPECT brain scanning is a sensitive, complementary diagnostic measure in the early detection, localization, and estimation of rCBF alterations in pediatric cerebrovascular disease.

Cerebrovascular Circulation↗

PubMed1990

Correlation of chromosome abnormalities with laboratory features and clinical course in B-cell chronic lymphocytic leukaemia.

141 patients with B-cell chronic lymphocytic leukaemia (B-CLL) have been studied for a minimum of 12 months and a maximum of 25 years. 30 of 133 patients (32.5%) had greater than 10% FMC7 positive peripheral blood lymphocytes and 19 of 131 patients (14.5%) had a serum or urinary paraprotein. At presentation 88 patients were stage A0, 18 A1, 18 A2, 11 B and six C. 44 (31%) had progressive disease and 42 (30%) died during the study period. 63 patients had a normal karyotype, 75 a clonal abnormality and in three no metaphases were obtained. The finding of a complex karyotypic abnormality was significantly associated with lambda surface phenotype (P less than 0.01), the presence of greater than 10% FMC7 positive cells (P less than 0.025), and the presence of a paraprotein (P = 0.025). Patients whose leukaemic cells had a complex karyotype and those with structural abnormalities of chromosomes 14 and 6 required treatment earlier than those with a normal karyotype.

Aged↗