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Biomedical subjects

R Lambert

Publications and source records attributed to R Lambert.

At least 55 records · Page 3Linked to original sources
PubMed1998

The captopril renogram: a new tool for diagnosing and predicting obstruction in childhood hydronephrosis.

PURPOSE: We evaluated the difference in response patterns of captopril versus standard renography for assessing hydronephrosis due to suspected ureteropelvic and ureterovesical junction obstruction. This technique may identify hydronephrotic kidneys in which normal function is maintained by vasoactive compensatory mechanisms. Sustained obstruction may cause these mechanisms to fail, and expose the kidneys to permanent functional deterioration in the long term. MATERIAL AND METHODS: We prospectively studied 15 boys and 8 girls with a mean age of 3.5 years with grades III to IV/IV hydronephrosis. Evaluations included renal sonography, standard diuretic and captopril renography, glomerular filtration rate, voiding cystography, serum creatinine, blood pressure, and urinalysis with culture and sensitivity. Obstruction was suspected at the ureteropelvic junction in 19 kidneys and at the ureterovesical junction in 9. We compared differential function values obtained by standard diuretic and captopril renography. RESULTS: We observed certain patterns in response to captopril renography, including pattern 1--unilateral decrease in hydronephrotic kidney relative function in 5 of 23 cases, 2--bilateral decreased function in 2, 3--bilateral increased function in 4 and 4--no change in function in 12 on standard renography. When half-time was more than 20 minutes on standard diuretic renography in 8 cases, captopril renography showed an ipsilateral decrease and bilateral increase in glomerular filtration rate in 4 and 1, respectively, and no change in 3. In 12 of the 23 patients (52%) there was no difference in the results of captopril and diuretic renography as well as no change in differential function on standard diuretic renography during 1 1/2 years of observation. Surgical correction was performed in 4 patients in whom half-time was greater than 20 minutes and differential function was decreased on captopril renography. CONCLUSIONS: Our preliminary study reveals that there may be a role for captopril renography for detecting renin-angiotensin system mediated compensatory mechanisms in obstructive uropathy. When such compensatory mechanisms are activated, they may be unmasked by captopril, producing 1 of 4 patterns on renography and glomerular filtration rate. Patterns may indicate different degrees of impending renal function impairment and, thus, they may become useful for determining the progression of injury, when present, and the appropriate timing of surgical intervention.

Captopril↗
PubMed1998

Cisapride 20 mg b.i.d. provides symptomatic relief of heartburn and related symptoms of chronic mild to moderate gastroesophageal reflux disease. CIS-USA-52 Investigator Group.

OBJECTIVE: We evaluated the efficacy and safety of a twice-daily dosage regimen of cisapride 20 mg in relieving the symptoms of mild-moderate gastroesophageal reflux disease (GERD) in patients with moderate intensity heartburn and no history of erosive esophagitis. METHODS: After a 2-wk, single-blind, placebo run-in period, 398 patients who continued to experience moderate intensity heartburn were randomized to either placebo (n = 196) or cisapride 20 mg (n = 202) twice daily for 4 wk. RESULTS: Compared with placebo, cisapride significantly reduced scores for daytime and nighttime heartburn (p < 0.001), total regurgitation (p < 0.001), eructation (p = 0.04), and early satiety (p = 0.04). Cisapride 20 mg b.i.d. was also superior to placebo in reducing total use of rescue antacid medication (p < 0.001); reducing, in concordance analyses, daytime and nighttime heartburn with antacid usage (p < 0.001); increasing the percentage of heartburn-free days and antacid-free nights (p < 0.5); and increasing the percentage of patients self-rated as having minimal or better symptomatic improvement (p = 0.01). Cisapride 20 mg b.i.d. was well tolerated. The most common adverse event in the cisapride group was diarrhea, reported by 10% of patients, compared with an incidence of 4% in the placebo group. CONCLUSION: Cisapride 20 mg b.i.d. was shown to be effective and safe for the short-term treatment of daytime and nighttime heartburn and for other symptoms associated with mild-moderate GERD.

Adolescent↗
PubMed1998

Metastatic axillary lymph node technetium-99m-MIBI imaging in primary breast cancer.

UNLABELLED: Technetium-99m-MIBI scintimammography has been shown to be useful in the detection of primary breast cancer. The purpose of this study was to evaluate the potential role of scintimammography in detecting axillary lymph node involvement in patients undergoing scintimammography to detect primary breast cancer. METHODS: A group of 100 women with breast cancer who were scheduled for a Level I-II axillary dissection were prospectively studied. Scintimammography was performed in all patients before histopathologic confirmation of breast cancer. Two lateral (prone imaging) views and one anterior (supine) planar thoracic view were obtained 10-15 min after the injection of 25-30 mCi 99mTc-MIBI (10 min/view) by using a special breast positioning device (foam cushion) placed over the imaging table. Both of the axilla were included in the field-of-view. Two experienced blinded observers reviewed all cases both from films and from the computer screen with contrast adjustment when needed. The site of intravenous injection of 99mTc-MIBI was known to the interpreters in order to avoid reading any false-positive uptake in the axilla ipsilateral to the injection site. RESULTS: A total of 52 patients had no axillary lymph node involvement (611 negative nodes) while 48 patients had at least one axillary lymph node with metastatic involvement (180/502 positive nodes). The sensitivity of scintimammography in detecting metastatic axillary lymph node involvement was 79.2% (38/48), and the specificity was 84.6% (44/52). The positive and the negative predictive values were 82.6% (38/46) and 81.5% (44/54), respectively. CONCLUSION: This study shows that scintimammography has good diagnostic accuracy for detecting axillary lymph node involvement in patients with breast cancer. This information should be added to the result of standard scintimammography, which requires very minor modifications in order to simultaneously evaluate both of the axilla.

Axilla↗
PubMed1998

An overview of the management of cancer of the esophagus.

The surgical treatment of esophageal cancer concerns a small percentage of patients with small Stage I or II tumors and a good performance status. Nonsurgical management with concurrent radiation and chemotherapy concerns a larger group of patients, and complete tumor responses have been observed at a significant rate. This applies to inoperable patients and to operable patients when there is a relative contraindication or when large malignant lymph nodes are detected at the preoperative stage. Endoscopic palliation in monotherapy should be restricted to the smallest possible number of patients.

Antineoplastic Agents↗
PubMed1998

Modification of Ca2+, Mg2+-ATPase and F-actin distribution in hepatocytes of cyclosporine A treated rats. Effect of soyabean lecithin and triacylglycerol.

We studied the effect of cyclosporine A on hepatic Ca2+, Mg2+-ATPase and F-actin on bile canalicular and basolateral membranes in rats fed either soyabean lecithin, or triacylglycerol enriched diet, or low fat diet. Ca2+, Mg2+-ATPase histochemical activity was not modified in lecithin-cyclosporine A group, whereas the activity was decreased in the other groups. The triacylglycerol-cyclosporine A group had the lower activity. The histochemical staining of F-actin was quite normal in lecithin-cyclosporine group but decreased in the other cyclosporine A treated groups. The lower staining was observed in the triacylglycerol-cyclosporine group. The alteration of Ca2+, Mg2+-ATPase and F-actin by cyclosporine A, related to cholestasis evidenced by a decrease in bile salt secretion, were prevented by dietary soyabean lecithin and amplified by dietary soyabean triacylglycerol.

Actins↗
PubMed1997

CD4+ T-cell testing practices as implications for training.

As new diseases and new testing methods emerge, clinical laboratories are faced with updating the skills of their personnel. Complex techniques, such as flow cytometry, require both education and experience to achieve a high level of proficiency. One of the ways to determine areas in which training is needed is to assess laboratory practices and compare them with practices recommended in guidelines or by panels of experts. In this paper we describe practices reported in a written survey of 206 laboratories that perform CD4+ T-cell counts (CD4). We provided a list of alternate practices for each of the key steps in the testing process and asked participants to select the practices they use in their laboratories. Published guidelines and interviews with knowledgeable "key informants" and focus groups of people who perform CD4 testing were used to formulate the questions. We interpreted variations from recommended practices as indicators of training needs. Other factors that can affect performance, such as workload, supervision, and resources, were satisfactory to the respondents. A response rate of 73% (247 of 337 laboratories) revealed that laboratories followed most of the recommended practices. Notable exceptions included some areas of quality control and quality assurance and safety. This paper also describes flow cytometry testing as it was practiced in 1993 shortly after release of some of the testing guidelines and provides a baseline of practices for that time frame.

Antibodies, Monoclonal↗
PubMed1997

Crystallization of 5-aminolaevulinic acid dehydratase from Escherichia coli and Saccharomyces cerevisiae and preliminary X-ray characterization of the crystals.

5-Aminolaevulinic acid dehydratase (ALAD) catalyzes the formation of porphobilinogen from two molecules of 5-aminolaevulinic acid. Both Escherichia coli and Saccharomyces cerevisiae ALADs are homo-octameric enzymes which depend on Zn2+ for catalytic activity and are potently inhibited by lead ions. The E. coli enzyme crystallized in space group I422 (unit cell dimensions a = b = 130.7 A, c = 142.4 A). The best crystals were obtained in the presence of the covalently bound inhibitor laevulinic acid. The yeast enzyme (expressed in E. coli) crystallized in the same space group (I422) but with a smaller unit cell volume (a = b = 103.7 A, c = 167.7 A). High resolution synchrotron data sets were obtained from both E. coli and yeast ALAD crystals by cryocooling to 100 K.

Crystallography, X-Ray↗
PubMed1997

Effect of cementless acetabular cup geometry on strain distribution and press-fit stability.

Use of cementless acetabular cups, which are slightly larger than the reamed acetabulum, can provide press-fit stability without screws; however, the ideal cup geometry to maximize stability is not clear. Acetabular strain distribution, deformation, and implant stability were studied using an axisymmetric finite-element model, and mechanical stability was assessed by testing lever-out and extraction forces required to displace different cup geometries from foam bones. The implants tested included four nonhemispheric cup geometries and 1- and 2-mm oversized hemispheric geometries. A nonhemispheric cup that provides a gradual transition from a hemisphere at the dome to a larger peripheral dimension appears to maximize peripheral strains and implant stability without increasing overall acetabular deformation as much as a larger oversized hemispheric cup.

Acetabulum↗
PubMed1997

X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolase.

5-Aminolaevulinate dehydratase (ALAD) is a homo-octameric metallo-enzyme that catalyses the formation of porphobilinogen from 5-aminolaevulinic acid. The structure of the yeast enzyme has been solved to 2.3 A resolution, revealing that each subunit adopts a TIM barrel fold with a 39 residue N-terminal arm. Pairs of monomers wrap their arms around each other to form compact dimers and these associate to form a 422 symmetric octamer. All eight active sites are on the surface of the octamer and possess two lysine residues (210 and 263), one of which, Lys 263, forms a Schiff base link to the substrate. The two lysine side chains are close to two zinc binding sites one of which is formed by three cysteine residues (133, 135 and 143) while the other involves Cys 234 and His 142. ALAD has features at its active site that are common to both metallo- and Schiff base-aldolases and therefore represents an intriguing combination of both classes of enzyme. Lead ions, which inhibit ALAD potently, replace the zinc bound to the enzyme's unique triple-cysteine site.

Amino Acid Sequence↗
PubMed1997

Review article: current practice and future perspectives in the management of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GERD) is primarily due to incompetence of the lower oesophageal sphincter (LOS) and crural diaphragm, with transient LOS relaxation frequently accounting for daytime reflux. In the absence of drugs that adequately correct the motility defects of GERD, treatment is directed towards decreasing gastric acidity. Oesophageal healing is related to control of 24-h intragastric acidity, the degree of acid suppression and duration of treatment. H2-receptor antagonists are generally less effective in GERD than in peptic ulcer disease. While providing symptomatic relief in non-erosive GERD, they are often ineffective in healing erosive oesophagitis. Proton pump inhibitors provide more rapid and complete healing and symptom resolution. They are superior to H2-receptor antagonists in the long-term management of erosive oesophagitis and in reducing recurrence of oesophageal stricture following mechanical dilatation. In Barrett's oesophagus, high-dose proton pump inhibitors in combination with laser/photodynamic ablation therapy can produce metaplastic regression, although this does not preclude future emergence of adenocarcinoma. Surgical morbidity and mortality rates in GERD generally remain higher than those associated with long-term pharmacotherapy. However, direct comparisons between laparascopic anti-reflux surgery and proton pump inhibitor maintenance therapy remain to be performed. Although there is no evidence that H. pylori infection worsens the severity of oesophagitis or that H. pylori is carcinogenic in the metaplastic oesophageal mucosa. It has been suggested that H. pylori-positive patients requiring long-term proton pump inhibitor therapy receive bacterial eradication therapy to reduce the risk of developing atrophic gastritis.

Anti-Ulcer Agents↗
PubMed1997

Coating of titanium alloy with soluble laminin-5 promotes cell attachment and hemidesmosome assembly in gingival epithelial cells: potential application to dental implants.

The formation of a biological seal around the transmucosal portion of dental implants may be crucial for the long-term success of these therapies. Data to date suggest that the gingival epithelium attaches to dental implants through the formation of hemidesmosomes. Biochemical and genetic data indicate that the laminin isoform, laminin-5, a component of basement membranes, plays a crucial role in the assembly and maintenance of hemidesmosomes. We report the use of soluble laminin-5 as a biological coating of titanium-alloy to promote cell attachment of the gingival epithelial cell line, IHGK. Monoclonal antibodies reactive with laminin-5 depleted the coating solution of all cell attachment activity and blocked cell attachment to laminin-5-coated disks. Immunodepletion with antibodies to fibronectin had no effect. Finally, we demonstrate that IHGK cells assembled hemidesmosomes within 24 h of attachment to laminin-5-coated titanium alloy but not to the titanium alloy alone. These results suggest that soluble laminin-5 may have clinical applications as a dental implant coating to promote the formation of a biological seal.

Alloys↗
PubMed1997

Analysis by confocal laser scanning microscopy imaging of undilated bile canaliculi F-actin staining in the hepatocytes of human extrahepatic cholestatic liver.

Many studies have demonstrated the role of bile canalicular microfilaments in bile secretion and bile flow. It is now admitted that modification of bile canalicular network of microfilaments play a role in dysfunction of bile secretion observed in many cases of cholestasis. This work intends to study F-actin, a major component of microfilaments, in human hepatocytes in extrahepatic cholestasis. Normal and extrahepatic cholestatic liver were studied. F-actin was stained with fluorescent phallotoxin and quantified by using confocal laser scanning microscopy and an image analysis method. Mean specific fluorescence (MSF) of bile canaliculi was measured. Since dilated and bile plugged canaliculi were rarely observed in cholestatic liver sections, only undilated bile canaliculi were analysed. Bile canalicular MSF was significantly increased (p < 0.05) in cholestatic hepatocytes (1.3 to 1.7 fold higher than in controls). These data demonstrate a pericanalicular thickening of F-actin microfilaments in human extrahepatic cholestatis, similar to that described in literature in many cases of human intrahepatic and extrahepatic cholestasis cases as well as in experimentally induced cholestasis. However, further studies are needed to understand this increase in F-actin pericanalicular microfilaments in human extrahepatic cholestasis.

Actin Cytoskeleton↗
PubMed1996

Chloroplastic aspartate aminotransferase from Arabidopsis thaliana: an examination of the relationship between the structure of the gene and the spatial structure of the protein.

A clone encoding a plastid isoenzyme of aspartate amino-transferase (AAT5) was isolated from an Arabidopsis genomic library and its complete sequence determined. The gene for AAT5 (asp5) contains an open reading frame of 2447 bp comprising 11 exons separated by introns ranging in length from 74 to 207 bp. The upstream regulatory region contains a putative TATA box and multiple copies of two sequence motifs, CTCTT and AAAGAT, previously associated with nodule-specific gene activity in legumes. The deduced primary amino acid sequence of the protein product of asp5 was used to generate a three-dimensional structure of the AAT5 protein by using the computer program Sybyl: Biopolymer Composer and known AAT structures on the protein databases. Both the mature protein and its precursor protein containing a putative N-terminal transit peptide were modelled. The resulting structure of the precursor protein indicated that the transit peptide might also inhibit dimerization of the protein until after its translocation across the chloroplast membrane. The derived structure of the mature protein was then analysed in terms of its component elements of secondary structure, and the positions on the polypeptide back-bone corresponding to intron insertion sites were determined. It is observed that the introns tend to map to regions between structural subdomains of the protein and also map to sites on the surface of the molecule. The asp5 gene in Arabidopsis is thus consistent with Gilbert's exon-shuffling theory of gene evolution [Gilbert (1985) Science 228, 823-824]. A high degree of conservation of intron insertion sites between AAT genes from different plants and animals is observed, particularly within the part of the gene encoding a large beta-sheet structure that forms the structural and functional core of the protein. This beta-sheet structure is thus believed to compromise an ancient and very highly conserved moiety of the molecule.

Amino Acid Sequence↗
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↗