Search PubMedSearch

Biomedical subjects

R Lambert

Publications and source records attributed to R Lambert.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

Motor activity of the sigmoid colon in chronic constipation: comparative study with normal subjects.

Manometric studies of the sigmoid colon were performed on 17 healthy volunteers and on 49 constipated patients, after a long period of fasting (18--20 hours). Motility was recorded using perfused catheters at basal level during 45 minutes, then 60 minutes after a 0.5 mg intravenous injection of neostigmine, and, finally, 30 minutes during and after a meal. Motor activity was assessed by a motility index (per cent of activity x mean amplitude of waves). In both normal and constipated patients, the basal motility index was very low (respectively 82 +/- 16 and 110 +/- 113). This low level of activity was due to the long fasting period imposed on all the subjects. After neostigmine the motility index increased in both controls (347 +/- 256) and constipated patients (311 +/- 325); this test, however was found to be unreliable. The meal increased the motility index to significantly higher values than after neostigmine in controls (538 +/- 215). In constipated patients the mean meal motility index was comparable with that of controls (577 +/- 549) with a large distribution of individual values. Using the mean meal motility index +/- 2 SD of the control group as a term of comparison, the patients were segregated into three groups: 'hypomotor' patients (eight cases), 'normomotor' patients (33 cases), and 'hypermotor' patients (eight cases). From the evidence of this series of clinically well-defined constipated patients, it was concluded that only the meal test is able to segregate three significant patterns of sigmoid activity and that a large number (68%) of constipated patients exhibit normal sigmoid motor activity.

Adolescent

Social work and dentistry in clinical, training and research collaboration.

The knowledge and knowledge building skills of social workers can improve in three ways the quality and type of services provided to dental patients. First, social workers can be involved in the training of dental professionals so as to improve their interactions with patients. Second, social workers may provide social work clinical services to dental patients. Finally, social workers can conduct research that can add to the body of knowledge on patient behaviors relevant to dental treatment. This paper outlines a program conducted by social workers that incorporates all three of these activities.

Dentistry

[Fibrorectosigmoidoscopy. Results of 476 cases (author's transl)].

A fibrorectosigmoidoscope, 60 cm in length has been systematically applied in the endoscopy unit to the exploration of the distal colon. Technical parameters have been analysed in 300 patients: --immediate enema preparation was satisfactory (95% of examinations), --tolerance was good (96% of examinations), --mean length of colon explored reached 48,5 cm, --mean length of duration reached 5,15 mn. Efficacy in the detection of colonic lesions was tested in 476 patients (symptomatic or asymptomatic). Tumoral lesions were detected in 105 patients, with a total of 125 adenomas and 31 cancers; 71 lesions were found in the area that could be explored by a rigid rectosigmoidoscope (0-19 cm) while 85 were beyond this limit (20-60 cm). The fibre endoscope explores a larger territory (rectum + sigmoid), resulting in increased efficacy in the detection of colonic lesions. It should therefore replace progressively the rigid instrument in spite of its higher cost.

Adenocarcinoma