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Biomedical subjects

R Lambert

Publications and source records attributed to R Lambert.

At least 73 records · Page 4Linked to original sources
PubMed1996

The three-dimensional structure of Escherichia coli porphobilinogen deaminase at 1.76-A resolution.

Porphobilinogen deaminase (PBGD) catalyses the polymerization of four molecules of porphobilinogen to form the 1-hydroxymethylbilane, preuroporphyrinogen, a key intermediate in the biosynthesis of tetrapyrroles. The three-dimensional structure of wild-type PBGD from Escherichia coli has been determined by multiple isomorphous replacement and refined to a crystallographic R-factor of 0.188 at 1.76 A resolution. the polypeptide chain of PBGD is folded into three alpha/beta domains. Domains 1 and 2 have a similar overall topology, based on a five-stranded, mixed beta-sheet. These two domains, which are linked by two hinge segments but otherwise make few direct interactions, form an extensive active site cleft at their interface. Domain 3, an open-faced, anti-parallel sheet of three strands, interacts approximately equally with the other two domains. The dipyrromethane cofactor is covalently attached to a cysteine side-chain borne on a flexible loop of domain 3. The cofactor serves as a primer for the assembly of the tetrapyrrole product and is held within the active site cleft by hydrogen-bonds and salt-bridges that are formed between its acetate and propionate side-groups and the polypeptide chain. The structure of a variant of PBGD, in which the methionines have been replaced with selenomethionines, has also been determined. The cofactor, in the native and functional form of the enzyme, adopts a conformation in which the second pyrrole ring (C2) occupies an internal position in the active site cleft. On oxidation, however, this C2 ring of the cofactor adopts a more external position that may correspond approximately to the site of substrate binding and polypyrrole chain elongation. The side-chain of Asp84 hydrogen-bonds the hydrogen atoms of both cofactor pyrrole nitrogens and also potentially the hydrogen atom of the pyrrole nitrogen of the porphobilinogen molecule bound to the proposed substrate binding site. This group has a key catalytic role, possibly in stabilizing the positive charges that develop on the pyrrole nitrogens during the ring-coupling reactions. Possible mechanisms for the processive elongation of the polypyrrole chain involve: accommodation of the elongating chain within the active site cleft, coupled with shifts in the relative positions of domains 1 and 2 to carry the terminal ring into the appropriate position at the catalytic site; or sequential translocation of the elongating polypyrrole chain, attached to the cofactor on domain 3, through the active site cleft by the progressive movement of domain 3 with respect to domains 1 and 2. Other mechanisms are considered although the amino acid sequence comparisons between PBGDs from all species suggest they share the same three-dimensional structure and mechanism of activity.

Amino Acid Sequence↗
PubMed1996

High-grade dysplasia in an adenoma of the upper esophagus developing on heterotopic gastric mucosa.

Patches of hererotopic gastric mucosa located in the upper esophagus are a frequent finding at endoscopy. These lesions are thought to be of congenital origin and of low malignant potential. However, several cases of adenocarcinoma developing on inlet patches have recently been described. We report here a new case of adenoma that had developed on heterotopic gastric mucosa in the upper esophagus, associated with an area of high-grade dysplasia. This polyp was removed surgically under endoscopic guidance, after confirmation of the superficial pattern of the lesion by endoscopic ultrasonography. This report emphasizes the malignant potential of esophageal inlet patches of heterotopic gastric mucosa.

Adenoma, Villous↗
PubMed1996

Extended harvest times are not necessary for the detection of in vitro clastogens in regulatory cytogenetics studies.

The choice of harvest time in in vitro cytogenetics assays is a critical factor in determining the sensitivity of the assay for detecting clastogenic potential. As yet there is no harmonization of regulatory requirements in this aspect. It has been suggested that the use of extended harvest times can improve the sensitivity of detecting some chemicals which either induce cell cycle delay or produce lesions which induce chromosome aberrations at divisions subsequent to the first post-treatment mitosis. The incidence of such chemicals encountered in the routine testing of chemicals for regulatory submissions is not known. Therefore a large database of 550 chemicals tested in nine laboratories using standard regulatory protocols, including a late harvest time, was assessed for the incidence of chemicals uniquely positive only at a delayed harvest time. The number of such chemicals was very low ( < 0.2%) and the chromosome damage induced by these chemicals may not result from direct genotoxic mechanisms. Based on these data it is recommended that there is no need to include an extended harvest time in in vitro cytogenetics assays except where it might help to resolve an equivocal result.

Animals↗
PubMed1996

"Cold" reflex sympathetic dystrophy in an adult.

The classical presentation of acute reflex sympathetic dystrophy (RSD) or triple-phase bone scintigraphy usually consists of increased periarticular uptake in each phase. The authors present a rare case of acute adult RSD characterized by bone hypofixation of Tc-99m MDP. Reflex sympathetic dystrophy in adults and children is reviewed.

Adult↗
PubMed1996

Prostaglandins and renal function in hypertensive patients with unilateral renal artery stenosis and patients with essential hypertension.

OBJECTIVE: This study was designed to compare the effects of prostaglandin synthesis inhibition on calculated preglomerular and postglomerular resistance in hypertensive patients with unilateral renal artery stenosis (RAS) and in patients with essential hypertension. DESIGN AND METHODS: Sixteen patients with suspected renovascular hypertension underwent renal angiography: eight had unilateral renal artery stenosis > or = 70% and eight had normal angiograms or stenosis < or = 40%. Radionuclide renography and 6 h urinary collection were performed twice for each subject, at baseline and after indomethacin administration. Levels of urinary vasodilatory prostaglandins were measured by specific radioimmunoassays. Visual image analysis was performed to determine the parenchymal transit time (PTT). The glomerular filtration rate (GFR) was calculated from the plasma clearance of [99mTc]-diethylenetriamine pentaacetic acid (DTPA). The preglomerular and postglomerular resistances were estimated according to Gomez's equations. RESULTS: The prostaglandin excretion decreased significantly after indomethacin administration both in RAS and in essential hypertension patients. The PTT increased from 230 +/- 10 to 340 +/- 40s in the stenotic kidney compared with the contralateral kidney and the kidneys of essential hypertension patients. The GFR was decreased both in stenotic and in contralateral kidneys (48 +/- 4 to 37 +/- 5 and 60 +/- 4 to 52 +/- 5 ml/min, respectively) but did not decline in the kidneys of essential hypertension patients. The preglomerular resistance increased both in stenotic and in contralateral kidneys, whereas it did not rise significantly in the kidneys of essential hypertension patients. The postglomerular resistance in stenotic and contralateral kidneys of RAS patients was not altered. CONCLUSIONS: Prostaglandins limit GFR decreases in RAS by preventing preglomerular constriction without interfering with postglomerular constriction. Thus, the action of vasoactive prostaglandins on preglomerular resistance might maintain renal function in the short term by limiting the fall in GFR in the stenotic kidney and by increasing the GFR in the contralateral kidney.

Blood Pressure↗
PubMed1996

[An orbital exostosis, the history of its removal and didactic presentation in the XIXth century and today ...].

During a meeting on Paleopathology an anatomic piece dating back to 1853 was presented by Dr Thillaud. It consisted of a right hemiskull, the orbital cavity of which was entirely filled by a bone tumour, which was considered as benignant according to all macroscopic paleopathological and radiological criteria. The situation of the tumour in the skeleton was surprising, considering the report in the Dupuytren Museum catalogue which mentioned its removal and a long survival of the patient after the operation. After some research, it was possible to find out all details of the case history, of the removal of the tumour and of its aberrant presentation in the skull which was solely done in a didactic purpose, as far back as 1853. This observation is a further proof of the interest of written documents in Paleopathology and of the evident connexion of this discipline with the History of Medicine.

Autopsy↗
PubMed1996

Radionuclide captopril renography in postpartum renal artery aneurysms.

We report the case of a young woman with three left renal artery aneurysms, diagnosed immediately postpartum, associated with a de novo high blood pressure. To assess anatomical and functional characteristics of renal artery aneurysms, renal angiogram, MRI, intravenous pyelography, ultrasonography and radionuclide renography were performed. Two patent saccular renal artery aneurysms were demonstrated in the left kidney by renal angiogram. A larger, thrombosed aneurysm was also depicted on the left side on ultrasonography, MRI and renal angiogram. The larger aneurysm was responsible for renovascular disease of the middle third of the kidney, as demonstrated by captopril and baseline radionuclide renographic studies. It also impeded drainage of the lower pyelocalyceal group, without obstructing it, as shown by concomitant furosemide (Lasix) evaluations.

Adult↗
PubMed1996

Radionuclide shuntogram: adjunct to manage hydrocephalic patients.

UNLABELLED: We reviewed our experience with shuntograms to establish technical criteria that would optimize the reliability of this test in managing patients with shunt malfunction. METHODS: Fifty-six shuntograms were performed in 47 children presenting with symptoms of shunt malfunction not elucidated by conventional radiological examination. Shuntograms were performed by injecting 0.5 ml 99mTc-DTPA in the reservoir of the shunt. RESULTS: There were 22 shuntograms in which ventricular reflux occurred and the entire shunt system was visualized. At surgery, three patients in this group presented partial obstruction of the ventricular and/or peritoneal catheter. A second group of patients had 15 shuntograms that showed normal proximal reflux but abnormal distal drainage. Ten patients in this group presented distal obstruction or fracture, valve dysfunction or peritoneal adhesions at surgery. A third group of patients with 19 shuntograms exhibited no proximal reflux. At surgery, twelve had an obstructed ventricular catheter and the last case showed overdrainage. Symptoms of nonsurgical patients abated spontaneously. CONCLUSION: The shuntogram is a useful procedure in the management of patients presenting with shunt-related problems. For consideration as a normal result, a shuntogram must exhibit ventricular reflux, the shunt system must be entirely visualized and the isotope must diffuse uniformly in the peritoneal cavity. Whereas rapid radionuclide clearance is a useful parameter in eliminating a distal obstruction. It is a misleading sign for proximal blockage. Absence of ventricular reflux is highly suggestive of proximal reflux. Implicit to this conclusion is the fact that the presence of a reservoir proximal to the valve greatly facilitates the performance and interpretation of a shuntogram.

Child↗
PubMed1996

Immunohistochemical detection of hepatitis C virus related C100-3 and core antigens in formalin-fixed liver tissue.

HCV C100-3 non-structural and core proteins have been detected by immunohistochemical methods on paraffin-embedded tissue sections using monoclonal antibodies in 22 cases of chronic hepatitis C. C100-3 protein was detected in cytoplasm and nuclei of hepatocytes whereas core protein was only detected in nuclei. The specificity of the nuclear localization of HCV antigens was discussed in relation to cross-reactivity of the anti core antibody with host-derived GOR antigen.

Antigens, Viral↗
PubMed1995

Technetium-99m antimyosin antibody (3-48) myocardial imaging: human biodistribution, safety and clinical results in detection of acute myocardial infarction.

Technetium-99m antimyosin (99mTc-AM) antibody imaging may have significant advantages over indium-111 antimyosin in clinical practice. The purpose of this study was to determine the human biodistribution, the safety profile and the sensitivity of 99mTc-AM (3-48) imaging in the detection of both Q-wave and non-Q-wave myocardial infarction (MI). Biodistribution and safety parameters were mainly determined in 12 normal healthy volunteers while 40 patients with proven MI (22 Q-wave, 18 non-Q-wave) were injected with 99mTc-AM (20-25 mCi) between 5 h and 7 days after the onset of acute chest pain. Three standard planar views were performed at 6 h and at 24 h post injection. Both sets of images were completed in 33 patients while two patients were imaged only at 6 h, three patients only at 18 h and one at 18 and 24 h. One patient was not imaged. Vital signs and ECG were recorded and blood samples for haematology, biochemistry and human antimurine antibodies (HAMA) and urinalysis were obtained in all volunteers and patients. No serious adverse reactions or side-effects attributable to 99mTc-AM have been reported. No volunteers or patients developed allergic reactions or significant increases in HAMA titres. Reading of 99mTc-AM imaging was performed by two blinded experienced observers. The sensitivity of 99mTc-AM in the detection of MI was 100% (21/21) for Q-wave and 83.3% (15/18) for non-Q-wave infarctions. The overall sensitivity was 92.3% (36/39). The three false-negative cases were inferoposterior MI. A certain degree of uptake focalization was seen in 26 out of 35 (74.2%) at 6 h. At 24 h, two patients (5.8%) did not show 99mTc-AM uptake while 22 (64.7%) showed intense focal uptake, seven (20.6%) moderate uptake and 3 (8.9%) slight uptake. It is concluded that 99mTc-AM (3-48) imaging is safe and shows high sensitivity in the detection of both Q-wave and non-Q-wave MI even with early imaging (6 h post injection). These promising results warrant further clinical investigation.

Adult↗
PubMed1995

A double-blind study of pantoprazole and ranitidine in treatment of acute duodenal ulcer. A multicenter trial. European Pantoprazole Study Group.

Pantoprazole is a new substituted benzimidazole, which is a potent inhibitor of gastric acid secretion by its inhibition of H+,K(+)-ATPase. Pantoprazole, 40 mg, was compared with the H2-receptor antagonist ranitidine, 300 mg, in the healing of acute duodenal ulcer. Two hundred seventy-six patients with endoscopically diagnosed duodenal ulcer were studied in this multicenter double-blind study. Patients were reendoscopied after two weeks of treatment, and those patients whose ulcers remained unhealed were also endoscoped after an additional two weeks of treatment. The primary end point was the complete healing of the ulcer. Demographic characteristics were comparable in both treatment groups. After two weeks of treatment, 90/124 (73%) patients in the pantoprazole group had healed ulcers compared with 57/126 (45%) patients in the ranitidine group (P < 0.001, per-protocol analysis). After four weeks, the cumulative healing rates were 92% and 84% in the pantoprazole and ranitidine groups, respectively (P = 0.073). Symptoms were also improved at week 2, with 84% and 72% of patients in the pantoprazole and ranitidine groups, respectively, reporting no ulcer pain (P < 0.05, per-protocol analysis). Both treatments were well tolerated. This study has confirmed the superiority of pantoprazole compared with ranitidine in the healing of duodenal ulcers and pain relief after two weeks of treatment and has shown pantoprazole to be well tolerated in this indication.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Long-term survival after photodynamic therapy for esophageal cancer.

BACKGROUND/AIMS: Photodynamic therapy (PDT) has been adapted to the endoscopic treatment of digestive cancer, but its indications and efficacy remain uncertain. The aim of this study was to assess its feasibility in the curative treatment of small esophageal tumors. METHODS: From 1983 to 1991, PDT was used to treat 123 patients with esophageal cancer who were recommended for nonsurgical treatment of squamous cell carcinoma (n = 104) and adenocarcinoma (n = 19). Endoscopic ultrasonography (EUS) was performed in 88 patients; 61 were staged uT1 and 27 were staged uT2. A hematoporphyrin derivative was injected 72 hours before laser irradiation with a 630-nm dye laser. PDT was applied alone in 56 patients and as part of a multimodal protocol in the 67 others. RESULTS: The complete response rate at 6 months was 87%. The 5-year survival rate was 25% +/- 6%, and the 5-year disease-specific survival rate was 74% +/- 5%. The complete response rate and survival rate were not different (1) between the PDT alone and the PDT multimodal treatment groups, (2) between the adenocarcinoma and squamous cell carcinoma groups, and (3) between the uT1 and uT2 EUS groups. PDT-related complications were esophageal stenosis (n = 43) and cutaneous photosensitization (n = 16). CONCLUSIONS: In patients with small esophageal tumors who pose high surgical risk, photodynamic therapy is an effective treatment.

Adenocarcinoma↗
PubMed1995

Thyroid scintigraphy in children and adolescents with Hashimoto disease.

Between 1989 and 1994, 58 children and adolescents with Hashimoto thyroiditis seen at the Sainte-Justine Hospital had thyroid scintigraphy. Their medical records and films were reviewed retrospectively. Eighty-nine percent of the patients had a homogeneous distribution of tracer on thyroid scintigraphy, unlike the heterogeneous distribution classically reported in adults. In children and adolescents, thyroid scintigraphy is not helpful in the diagnosis of typical Hashimoto thyroiditis.

Adolescent↗
PubMed1995

Endoscopic detection and treatment of early esophageal cancer: a critical analysis.

Early-stage esophageal cancer is almost asymptomatic. The endoscopic findings are minimal, and there is no esophageal stenosis. However, a risk of malignant propagation into vessels and lymph nodes is present in small tumors. Endoscopic destruction or resection should be performed only at the predissemination stage. We present here a critical analysis of whether endoscopic detection and treatment is feasible and efficacious, based on the pathology of esophageal tumors.

Carcinoma, Squamous Cell↗
PubMed1995

A physiologic approach to renal scintigraphy. Application to evaluation of hypertension.

The aim of this study was to define the use of the triple radiopharmaceutical renal study (TRRS) for renal scintigraphy as a physiological tool for renal evaluation, and to determine if the sensitivity and/or specificity of a renal study for the diagnosis of renovascular hypertension (RVH) could be improved by the combination of three radiopharmaceuticals (i.e., I-131 OIH, Tc-99m DTPA, and Tc-99m glucoheptonate). One hundred ninety-five patients with suspected RVH underwent TRRS, standard Tc-99m DTPA renal studies, and renal angiography. One hundred eighty-nine patients were hypertensive and ischemic nephropathy was suspected in six. Ninety-one, including three patients with ischemic nephropathy, had a renal artery stenosis of 70% or more (66 unilateral, 25 bilateral). Effective renal plasma flow (ERPF), glomerular filtration rate (GFR) (from plasma clearance of I-131 OIH and Tc-99m DTPA), and geometric renal masses (from Tc-99m glucoheptonate study) were compared to normal values corrected for body surface, to determine the severity of renal dysfunction. For the TRSS, RVH criteria included: 1) differential Tc-99m DTPA function minus differential Tc-99m glucoheptonate function of affected kidney ( < -5% or > 5%) and 2) functional parameters: ERPF = 1.6-2.0 ml/g/minute, GFR = 0.25-0.4 ml/g/minute, and filtration fraction (i.e., GFR/ERPF = 0.15-0.20) on the affected side.

Aged↗