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Biomedical subjects

R Lambert

Publications and source records attributed to R Lambert.

At least 91 records · Page 5Linked to original sources

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↗

Cartilaginous airway dimensions and airflow obstruction in human lungs.

Airway wall remodeling in asthma and chronic obstructive pulmonary disease (COPD) can have a profound effect on the function of the airways. We tested the hypothesis that airflow obstruction and estimates of peripheral airway inflammation correlate with airway wall thickness and the amount of bronchial smooth muscle in cartilaginous airways. In addition, we estimated the theoretical relation between airway dimensions and airway resistance with a computational model. Lung tissue was obtained from 72 patients with different degrees of COPD who were operated on for a solitary peripheral lung lesion. In 341 transversely cut cartilaginous airway sections we measured airway size and airway wall dimensions. Inflammatory changes from the same lungs were scored in noncartilaginous airways. Preoperatively measured maximum expiratory flows and the response to a bronchodilator were correlated with airway wall dimensions. Maximum expiratory flow, the reversibility of airflow obstruction, and peripheral airway inflammation were significantly related to the airway wall area but not to the smooth muscle area. We conclude that airflow obstruction and its reversibility in COPD is in part caused by thickening of the cartilaginous airway wall and is related to inflammatory changes.

Airway Resistance↗

Right-hemisphere dysfunction in Asperger's syndrome.

Asperger's syndrome has many clinical features in common with acquired right-hemisphere dysfunction and has been postulated to result from a developmental abnormality of the right hemisphere. However, right-hemisphere abnormality has not previously been documented on neuroanatomic or functional imaging in patients with Asperger's syndrome. We report three patients with Asperger's syndrome found to have abnormal right-hemisphere function on single photon emission computed tomographic (SPECT) imaging. The subjects were two males and one female, ranging from 12 to 16 years of age. All were diagnosed on the basis of the presence of the complete constellation of clinical features previously outlined. All patients were investigated with computed tomographic (CT) scanning, magnetic resonance imaging (MRI), and SPECT scanning. In one subject, CT and MRI revealed enlargement of the right lateral ventricle, reflecting a mild degree of right hemispheric atrophy. CT and MRI studies on the other two subjects were normal. SPECT scanning demonstrated right hemispheric abnormalities in each subject: right temporal hypoperfusion with a central area of increased perfusion along with frontal polar hyperperfusion in one; diffusely decreased right hemispheric uptake in the second; and decreased frontal and occipital uptake in the third. Cerebellar abnormalities were also present: a smaller right hemisphere with increased uptake in the first; decreased uptake in the vermis and right hemisphere in the second; and decreased vermal uptake in the third. These findings support the hypothesis that the neurobiologic basis of Asperger's syndrome is a developmental abnormality of the right cerebral hemisphere.

Adolescent↗

Functional status and the use of formal home care in the year before death.

A national sample of persons who died in 1986 was analyzed to obtain a valid estimate of the relationship between functional status and the provision of formal home care during the last year of life. Community-based care has become increasingly important as the size of the elderly population increases and the cost for institutional care rises. When people need help in caring for themselves because of illness, frailty, or disability, community-based care may be more appropriate than acute or institutional care. The year before death is often a time of dependence and a high intensity of health service consumption. Although care at home is provided primarily by families, formal home care is also a critical component in any continuum of care.

Activities of Daily Living↗

Technetium-99m-sestamibi prone scintimammography to detect primary breast cancer and axillary lymph node involvement.

UNLABELLED: The purpose of this study was to evaluate prospectively the sensitivity and specificity of scintimammography in the detection of both primary breast cancer and axillary lymph node involvement. METHODS: Sixty-five consecutive women referred for a suspicious breast lesion on clinical examination and/or with abnormal mammographies suggestive of malignancies were studied with scintimammography using planar prone imaging (with a chest positioning device with semicircular lateral aperture on the imaging table) performed 15 min postinjection of 25-30 mCi 99mTc-sestamibi. Three planar views, right and left lateral prone and anterior supine thoracic views, were obtained (8-10 min/view). The entire breast and ipsilateral axillary region were included in the field of view. Excisional breast biopsy and/or fine needle aspiration cytology were performed in all patients within 4 wk after scintimammography. Axillary node dissection was also performed. RESULTS: The largest primary tumor measured 2 x 3 cm. There were 47 primary breast cancers (8 different histologic types) and 18 benign breast lesions (5 histologic types). The sensitivity of scintimammography for detecting primary breast cancer was 91.5% (43 true-positive, 4 false-negative) and the specificity was 94.4% (17 true-negative, 1 false-positive). Metastatic axillary lymph node involvement was seen in 19 of 41 patients. The sensitivity of scintimammography to detect metastatic lymph nodes was 84.2% (16 true-positive, 3 false-negative) and the specificity was 90.9% (20 true-positive, 2 false-positive). CONCLUSION: This preliminary study confirms the results of some previous reports, which showed the high diagnostic accuracy of scintimammography in detecting breast cancer. This study also shows the potential value of this procedure to detect axillary lymph node involvement as concomitant information.

Axilla↗

Structural studies on porphobilinogen deaminase.

The X-ray crystallographic analysis of porphobilinogen deaminase (hydroxymethylbilane synthase, EC 4.3.1.8) shows the polypeptide chain folded into three domains, (1) N-terminal, (2) central and (3) C-terminal, of approximately equal size. Domains 1 and 2 have a similar overall topology, a modified doubly wound parallel beta-sheet. Domain 3 is an open-faced three-stranded antiparallel beta-sheet, with one face covered by three alpha-helices. The active site is located between domains 1 and 2. The dipyrromethane cofactor linked to cysteine 242 protrudes from domain 3 into the mouth of the cleft. Flexible segments between domains 1 and 2 are thought to have a role in a hinge mechanism, facilitating conformational changes. The cleft is lined with positively charged, highly conserved, arginine residues which form ion pairs with the acidic side chains of the cofactor. Aspartic acid 84 has been identified as a critical catalytic residue both by its proximity to the cofactor pyrrole ring nitrogen and by structural and kinetic studies of the Asp-84-->Glu mutant protein. The active site arginine residues have been altered by site-directed mutagenesis to histidine residues. The mutant proteins have been studied crystallographically in order to reconcile the functional changes in the polymerization reaction with structural changes in the enzyme.

Crystallography, X-Ray↗

The three-dimensional structures of mutants of porphobilinogen deaminase: toward an understanding of the structural basis of acute intermittent porphyria.

Mutations in the human gene for the enzyme porphobilinogen deaminase give rise to an inherited disease of heme biosynthesis, acute intermittent porphyria. Knowledge of the 3-dimensional structure of human porphobilinogen deaminase, based on the structure of the bacterial enzyme, allows correlation of structure with gene organization and leads to an understanding of the relationship between mutations in the gene, structural and functional changes of the enzyme, and the symptoms of the disease. Most mutations occur in exons 10 and 12, often changing amino acids in the active site. Several of these are shown to be involved in binding the primer or substrate; none modifies Asp 84, which is essential for catalytic activity.

Amino Acid Sequence↗

Endoscopic ultrasonography in the preoperative staging of esophageal cancer.

Endoscopic ultrasonography is the best available method for the locoregional staging of esophageal carcinoma. Its main limitations are represented by a) tumor stenosis, b) distinguishing between malignant and benign lymph nodes, and c) distinguishing between mucosal and submucosal cancer. In untreated esophageal carcinoma, three main groups can be distinguished, based on clinical and morphological evaluation (endoscopy, abdominal ultrasound and CT). EUS is not useful when palliative treatment aiming to relieve dysphagia is the only treatment. In tumors with a superficial pattern at endoscopy, EUS is necessary to distinguish T1 from more invasive tumors, but endoscopic treatment (photodynamic therapy, strip biopsy) is indicated only in nonsurgical patients. In the last, and largest, group of tumors with no clear surgical contraindication, EUS is necessary when surgery is not the only treatment considered. EUS staging then improves patient management (surgery alone, surgery with preoperative treatment, or nonsurgical treatment; type of surgery). Moreover, it provides a good evaluation of the prognosis, and allows better follow-up after nonsurgical treatment.

Esophageal Neoplasms↗

[Misoprostol in the prevention of gastric erosions caused by nonsteroidal anti-inflammatory agents].

A multicenter, double-blind, placebo-controlled study was carried out to determine whether the synthetic prostaglandin E1 analog misoprostol is effective in preventing gastric and duodenal lesions induced by nonsteroidal anti-inflammatory drugs. Two hundred fifty-six patients under nonsteroidal anti-inflammatory drug treatment (diclofenac, naproxen, piroxicam, ibuprofen, indomethacin, ketoprofen, or tiaprofenic acid) for osteoarthritis, rheumatoid arthritis, or other rheumatic diseases were included in the study. None of the patients had patent gastroduodenal damage at entry (0 to 3 mucosal erosions or subepithelial hemorrhages on endoscopy). Patients were randomly assigned to treatment with misoprostol 400 micrograms/d (M 400), misoprostol 800 micrograms/d (M 800) or a placebo. Results of the follow-up endoscopy on day 28 in the 186 evaluable patients showed that gastric erosions were significantly less common (p < or = 0.02) in the two misoprostol groups (5% and 2% in the M 400 and M 800 groups respectively) than in the placebo group (19%). Similar small numbers of patients in the three groups had gastric subepithelial hemorrhages or duodenal lesions. Three patients developed gastric ulcers in the placebo group, versus none in the misoprostol groups. Misoprostol therapy did not modify the efficacy of the nonsteroidal antiinflammatory agent on pain or other rheumatologic manifestations. Diarrhea occurred in 1%, 10%, and 5% of patients in the M 400, M 800, and placebo groups, respectively. In conclusion, misoprostol given in combination with a nonsteroidal anti-inflammatory agent for 28 days significantly reduced the incidence of gastric erosions in a random sample of patients with a variety of rheumatic diseases. The daily dosage associated with the best risk/benefit ratio may be 400 micrograms/day.

Anti-Inflammatory Agents, Non-Steroidal↗

Characterization of wear in composite material orthopaedic implants. Part I: The composite trunnion/ceramic head interface.

Carbon fiber reinforced polyetheretherketone (C/PEEK) composite materials are being investigated as an alternative to metal in the femoral component of a total hip arthroplasty. Wear is among the issues that must be addressed before introducing a new orthopaedic implant material. This study examines the generation of wear debris when zirconia femoral heads are mechanically attached to C/PEEK trunnions and loaded under simulated physiological conditions. Mechanical testing was performed on a trunnion/head assembly loaded from 445 to 4450N at an angle of 39 degrees to the long axis of the trunnion. The trunnions were tested at a frequency of 20 Hz for 10 million cycles. After completion of the fatigue test, solution from the test assembly was characterized by laser scattering and by SEM image analysis to determine the size, shape, total number, and identify of the particles. In addition, the peak load to pull the head from the trunnion was measured. The total number of particles generated during the test was in the range of 10(5) as indicated by both laser scattering and (SEM) image analysis. Both carbon fiber and PEEK particles were found in an average proportion of about 1:13, respectively. The carbon fiber particle size average was 153 microns and the PEEK particle size average was 2.2 microns. The zirconia heads remained well attached to the C/PEEK trunnions as indicated by a mean peak distraction force of 1942 +/- 116N.

Benzophenones↗

Thallium-201-dipyridamole imaging: comparison between a standard dose and a high dose of dipyridamole in the detection of coronary artery disease.

UNLABELLED: The purpose of this study was to compare two different doses of dipyridamole as a pharmacologic stress test for 201Tl imaging. METHODS: Twenty-four patients with significant coronary artery disease (15 had undergone a coronary angiogram and 9 had undergone a previous 201Tl study with a significant lesion) were prospectively studied. Within 1 wk, all patients underwent two 201T-dipyridamole myocardial planar studies, one using a standard dose (STD) and the other, a high dose (HIGH) of dipyridamole. The protocol order was randomly assigned. The STD protocol used a dose of 0.14 mg/kg/min for a duration of 4 min (0.56 mg/kg), and the HIGH protocol used a dose of 0.14 mg/kg min for a duration of 6 min (0.84 mg/kg). The 201Tl was injected 3 min after the end of the dipyridamole infusion. Images, obtained 5 min and 4 hr later, were interpreted (divided into five segments each) by three blinded observers. RESULTS: The STD protocol showed normal, ischemia and scar in 252, 91 and 17 segments, respectively. The HIGH protocol detected 232, 118 and 10 segments, respectively. A side-by-side evaluation was done to evaluate the defect extent subjectively, which was greater with HIGH in 14, equal in six and smaller in four patients. One or more side effects were seen in 14 patients with STD and in 19 with HIGH. Increased heart rate (8 bpm for STD and 19 bpm for HIGH, p < 0.001) was the only significant change seen in the hemodynamic parameters. CONCLUSION: This preliminary study indicates that a high dose of dipyridamole seems to be safe and can be helpful to increase the sensitivity of 201Tl imaging.

Coronary Disease↗

Receptor imaging with atrial natriuretic peptide. Part 1: High specific activity iodine-123-atrial natriuretic peptide.

METHODS: Atrial natriuretic peptide (ANP) was labeled in high specific activity using 123I (p,2n). The biodistribution of 123I-ANP was studied in green vervet monkeys by gamma scintigraphy and in rats by dissection and gamma counting. Iodine-125-ANP was also studied in monkeys by in vitro autoradiography. RESULTS: Iodine-123-ANP showed rapid blood clearance with localization to ANP receptors in the kidneys and lungs, which accounted for 35% of total uptake. In vivo competition imaging studies using cold ANP99-126 and C-ANP102-121 proved that uptake is receptor mediated and allowed imaging of the differential biodistribution of A/B and C-ANP receptor families. Thus, it was possible through the use of selective receptor occupation to prevent uptake in certain organs and to effectively steer the labeled ANP to others. The observed biodistribution patterns were confirmed by an in vitro study using 125I-ANP in the same monkeys, which correlated the scintigraphic images with receptor distribution. An in vivo biodistribution study in rats showed a profound effect of specific activity on biodistribution, with a cutoff for receptor uptake at less than 3000 Ci/mmole. CONCLUSION: Gamma scintigraphy with 123I-ANP permits the imaging of ANP receptors in vivo. In contrast to receptor imaging with either organic molecules or antibodies, ANP provides rapid first-pass uptake and substantial accumulation (%dose/organ approximately 20% or greater) in receptors. The key to receptor imaging with peptides is high specific activity. Labeled ANP offers potential as a diagnostic tool for diabetic nephropathy, particularly for quantifying the involvement of glomerular disease.

Animals↗

Mutagens, N-nitroso compounds and their precursors in gastric juice from patients with and without precancerous lesions of the stomach.

This study examined whether elevated risk of gastric cancer is associated with high levels of total N-nitroso compounds (NOC), their precursors and nitrosation-dependent genotoxins in gastric juice (GJ). An improved method for quantifying total NOC was used and genotoxicity was assayed in E. coli. Results from patients (n = 210) with or without precancerous lesions of the stomach and living in three areas with up to 8-fold variations in gastric cancer risk (U.K., France, Colombia) were compared. The level of nitrite (range < 1-472 mumol/l) was found to increase with the pH of GJ from the three countries and was dependent on country of collection. The levels of NOC (range: < or = 0.01-8.0 mumol/l) in GJ were not affected by stomach histology and country of collection. NOC levels increased linearly with nitrite concentrations, but the slope of the regression line was greater for acidic GJ (pH < or = 4). These data together suggest that chemical nitrosation contributes at least as much as other nitrosation pathways to the intragastric formation of NOC. Acid-catalysed nitrosation of GJ in vitro increased the NOC concentration (range: 7-1332 mumol/l) up to several 1000-fold but this increase was not predictive of gastric cancer risk either by country or by stomach histology. After acid-catalysed nitrosation, direct genotoxicity (SOS-inducing potency) was significantly higher in GJ with original pH > 4 and highest in samples from Colombia. The results (a) provide no support that intragastric total NOC levels are elevated in subjects with precancerous stomach lesions or living in a high risk area for stomach cancer; (b) confirm that a high nitrite level and elevated pH in GJ are strongly associated, the level of nitrite being associated with precancerous stomach conditions only in Colombia; (c) reveal the presence of precursor compounds in GJ, that after nitrosation yield direct mutagens that probably contain NOC and other substances. As their concentrations were significantly higher in achlorhydric subjects and highest in Colombian patients, these data together provide support for a role of intragastrically formed nitrite-derived direct mutagens in gastric cancer aetiology.

Adult↗

Echoendoscopy prior to endoscopic tumor therapy--more safety?

Echoendoscopy has been found useful to better define gastrointestinal tract tumors which may be suitable for endoscopic treatment. In benign tumors, echoendoscopy may be used to decrease the risk of hemorrhage or perforation before resection of large polyps or submucosal lesions. The most important indications for echoendoscopy, however, are in the field of GI oncology, and the method may lead to a better selection of superficial cancers without lymph node metastases. However, endoscopic ultrasound is still limited in differentiating mucosal from submucosal tumors and in the detection and interpretation of small lymph nodes. Technical improvements and careful interpretation of echoendoscopy will increase the number of patients cured by non-surgical procedures in the future.

Colorectal Neoplasms↗