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Biomedical subjects

J Barrett

Publications and source records attributed to J Barrett.

At least 127 records · Page 7Linked to original sources

Novel technetium-99m-labeled platelet GPIIb/IIIa receptor antagonists as potential imaging agents for venous and arterial thrombosis.

OBJECTIVES: Either venous or arterial thrombosis is a potentially life-threatening event and existing diagnostic modalities are inadequate to diagnose and to determine the morphology of the evolving thrombus. Thus development of a noninvasive imaging agent that can detect clot location remains a critical and unmet need in nuclear diagnostic medicine. The present study was undertaken to determine the potential of platelet GPIIb/IIIa receptors compared with direct thrombin inhibitors, in the detection of venous and arterial clots. METHODS: Initially, the validity of exploiting the degree and extent of specific uptake and retention of a potent GPIIb/IIIa receptor antagonist in venous and in arterial thrombus was confirmed in vitro in artificially created arterial- or venous-type clots, using the radiolabeled antagonist, 3H-DMP728. This was followed by comparing the in-vivo clot/blood distribution of various technetium-99m (99mTc)-labeled, DMP728-derived, GPIIb/IIIa receptor antagonists and of thrombin inhibitors, over time, in mixed arterial/venous or venous clots in arteriovenous shunt and in venous clot models in dogs. In addition, we performed noninvasive single-photon emission tomographic imaging of the venous clot in a deep vein thrombosis model in dogs. RESULTS: Our data confirmed that potency for the platelet GPIIb/IIIa receptors was maintained after radiolabeling of the parent active GPIIb/IIIa receptor antagonists. DMP728 demonstrated a relatively greater affinity for activated than for unactivated human platelets, which might be essential for attaining an optimal thrombus/blood (target/background) distribution ratio and the optimal detection of small clots (i.e. greater sensitivity). CONCLUSIONS: These data suggest a potential utility of 99mTc-GPIIb/IIIa receptor antagonists, but not of direct thrombin inhibitors, in the diagnosis of venous clots in deep vein thrombosis, pulmonary embolism and arterial thromboembolic disorders including stroke and coronary and peripheral artery thrombotic disorders.

Analysis of Variance↗

Sphingomyelin synthesis in helminths: a minireview.

Sphingolipids are a diverse and ubiquitous group of lipids. They are widely distributed in parasites and a number of novel forms have been described. Sphingolipid synthesis has been investigated in the malarial parasite, cestodes, digeneans and nematodes. Although there are differences in detail, the synthetic pathways involved are similar to those found in mammals.

Animals↗

Characterisation and properties of an intracellular lipid-binding protein from the tapeworm Moniezia expansa.

The tapeworm Moniezia expansa contains an extremely abundant cytoplasmic lipid-binding protein (LBP). It is a small protein consisting of 66 amino acids with a molecular mass of 7943 +/- 1.5 Da. The amino acid sequence has been established by Edman degradation and confirmed by PCR analysis. The Moniezia LBP shows no sequence similarity with any previously described binding protein, but does show similarity with antigen B from Echinococcus glanulosus and Echinococcus multilocularis and with Taenia crassiceps antigen. The predicted structure for Moniezia LBP shows four helices and a putative tyrosine kinase site on the loop between helix 1 and 2. Each of the four helices has a well defined hydrophobic face. Studies with fluorescent probes suggest a single hydrophobic binding site. Results indicate that the single tryptophan residue in the molecule (Trp41) is involved in ligand binding, and calculation of the Stern-Volmer quenching constant shows that Trp41 is in a relatively hydrophobic environment.

Amino Acid Sequence↗

Effects of aerosolized surfactant in patients with stable chronic bronchitis: a prospective randomized controlled trial.

CONTEXT: Chronic bronchitis, estimated to affect more than 13 million adults in the United States, is characterized in part by retention of airway secretions, but no approved or effective therapy for airway mucus retention in patients with chronic bronchitis has been established. Surfactant reduces sputum adhesiveness, which contributes to difficulty in clearing secretions, but surfactant has not been tested in patients with chronic bronchitis. OBJECTIVE: To examine the effects of exogenous surfactant on sputum clearance and pulmonary function in patients with stable chronic bronchitis. DESIGN: A prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled comparison of the effects of 2 weeks of treatment with 3 doses of aerosolized surfactant (palmitoylphosphadidylcholine [DPPC]) or saline (placebo). SETTING: Four US teaching hospitals. PARTICIPANTS: A total of 87 adult patients with the diagnosis of stable chronic bronchitis. MAIN OUTCOME MEASURES: Pulmonary function, respiratory symptoms, and sputum properties before treatment (day 0), after 2 weeks of treatment (day 14), and 7 days after stopping treatment (day 21). RESULTS: A total of 66 patients were randomized to surfactant treatment and 21 to saline treatment. Patient demographic characteristics between groups were similar at baseline. In patients who received a DPPC dose of 607.5 mg/d for 2 weeks, prebronchodilator forced expiratory volume in 1 second (FEV1) increased from 1.22 L (SEM, 0.08 L) at day 0 to 1.33 L (SEM, 0.09 L) at day 21 (P=.05), an improvement of 11.4%; postbronchodilator FEV1 improved 10.4% by days 14 and 21 (P=.02); and the ratio of residual volume to total lung capacity, a measure of thoracic gas trapping, decreased 6.2% by day 21 (P=.009). In the surfactant groups, there was a dose-dependent increase in the ability of sputum to be transported by cilia in vitro. CONCLUSION: Aerosolized surfactant improved pulmonary function and resulted in a dose-related improvement in sputum transport by cilia in patients with stable chronic bronchitis.

Administration, Intranasal↗

Plaque radiotherapy for the management of uveal metastasis.

BACKGROUND: Radiotherapy is effective for the management of most uveal metastases, and standard external beam radiotherapy is generally administered during a 3-to 4-week period. For those patients in whom external beam radiotherapy or other methods fail or those patients with solitary uveal metastases, plaque radiotherapy may be an alternative method. OBJECTIVE: To determine the effectiveness of plaque radiotherapy for the management of uveal metastasis. METHODS: A retrospective review of 36 patients with uveal metastases who were examined at the Oncology Service at Wills Eye Hospital, Philadelphia, Pa, and treated with plaque radiotherapy. The clinical findings and follow-up data of the primary tumor and the uveal metastasis were analyzed. RESULTS: Of the 36 patients, 27 (75%) received plaque treatment as primary therapy for the uveal metastasis and 9 (25%) received plaque treatment as secondary therapy after failure of the uveal tumor to respond to external beam radiotherapy, chemotherapy, or hormonal therapy. During treatment, 22 patients (61%) had no other systemic metastasis and 14 (39%) had controlled systemic metastasis. No patients had active metastasis elsewhere. The uveal metastasis was solitary and well circumscribed in all but 1 patient; it measured a mean of 11 mm in basal dimension and 4 mm in thickness. The mean time for treatment was 86 hours, and the mean therapeutic dose was 68.80 Gy to the tumor apex and 235.64 Gy to the tumor base. Regression of the uveal metastasis was documented in 34 patients (94%) during a mean follow-up of 11 months. As early as 3 months after treatment, the mean tumor thickness had decreased to 2 mm. Plaque radiotherapy salvaged 5 of the 6 eyes that had failed prior external beam radiotherapy. Radiation retinopathy, radiation papillopathy, or both were found in 3 patients (8%) and occurred at a mean of 8 months after treatment. At the last examination, 18 patients (50%) were alive (11 with and 7 without active systemic metastasis) and 18 (50%) were dead from systemic metastasis. CONCLUSIONS: Plaque radiotherapy is an effective method for treating selected solitary uveal metastasis. It offers a high degree of tumor control, especially for those eyes in which other methods have failed. Plaque treatment is provided during a short period, minimizing the time demand for these patients with a limited life expectancy.

Adult↗

Sensitivity and positive predictive value of Medicare Part B physician claims for rheumatologic diagnoses and procedures.

OBJECTIVE: To examine the sensitivity and positive predictive value of Medicare physician claims for select rheumatic conditions managed in rheumatology specialty practices. METHODS: Eight rheumatologists in 3 states abstracted 378 patient office records to obtain information on diagnosis and office procedures. The Medicare Part B physician claims for these patient visits were obtained from the Health Care Financing Administration. The sensitivity of the claims data for a specific diagnosis was calculated as the proportion of all patients whose office records for a particular visit documented that diagnosis and who also had physician claims for that visit which identified that diagnosis. The positive predictive value was evaluated in a separate sample of 331 patient visits identified in Medicare physician claims. The positive predictive value of the claims data for a specific diagnosis was calculated as the proportion of patients with that diagnosis coded in the claims for a particular visit who also had the diagnosis documented in the medical record for that visit. RESULTS: Ninety percent of abstracted office medical records were matched successfully with Medicare physician claims. The sensitivity of the Medicare physician claims was 0.90 (95% confidence interval [CI] 0.85-0.95) for rheumatoid arthritis (RA), 0.85 (95% CI 0.73-0.97) for systemic lupus erythematosus (SLE), and 0.85 (95% CI 0.78-1.0) for aspiration or injection procedures. The sensitivity for osteoarthritis (OA) of the hip or knee was < or = 0.50 if 5-digit codes specifying anatomic site were required. The sensitivity for fibromyalgia (FM) was 0.48 (95% CI 0.28-0.68). The positive predictive values were at least 0.90 for RA, SLE, and aspiration or injection procedures. Positive predictive values for FM and the 5-digit site-specific codes for OA of the knee were 0.83 (95% CI 0.66-1.0) and 0.88 (95% CI 0.75-1.0), respectively, while the positive predictive value of the 5-digit site-specific codes for OA of the hip was zero (95% CI 0-0.26). The positive predictive value of OA at any site was 0.83 (95% CI 0.76-0.90). CONCLUSION: In specialty practice, Medicare physician claims had high sensitivity and positive predictive value for RA, SLE, OA without specification of anatomic site, and injection or aspiration procedures. The claims had lower sensitivity and predictive value for FM and for OA of the hip. The accuracy of Medicare physician claims for other conditions and in the primary care setting requires further investigation.

Aged↗

Parasite sulphur amino acid metabolism.

This paper reviews current knowledge regarding the metabolism of the sulphur-containing amino acids methionine and cysteine in parasitic protozoa and helminths. Particular emphasis is placed on the unusual aspects of parasite biochemistry which may present targets for rational design of antiparasite drugs. In general, the basic pathways of sulphur amino acid metabolism in most parasites resemble those of their mammalian hosts, since the enzymes involved in (a) the methionine cycle and S-adenosylmethionine metabolism, (b) the trans-sulphuration sequence, (c) the transminative catabolism of methionine, (d) the oxidative catabolism of cysteine and (e) glutathione synthesis have been demonstrated variously in several helminth and protozoan species. Despite these common pathways, there also exist numerous differences between parasite and mammalian metabolism. Some of these differences are relatively subtle. For example, the biochemical properties (and primary amino acid structures) of certain parasite methionine cycle enzymes and S-adenosylmethionine decarboxylases differ from those of the corresponding mammalian enzymes, and nematodes and trichomonads possess a novel, non-mammalian form of the trans-sulphuration enzyme cystathionine beta-synthase. The most profound differences between parasite and mammalian biochemistry relate to a number of unusual enzymes and thiol metabolites found in parasitic protozoa. In certain protozoa the pathway for methionine recycling from 5'-methylthioadenosine differs markedly from the mammalian route, and involves 2 exclusively microbial enzymes. Trypanosomatid protozoa contain the non-mammalian antioxidant thiol compounds ovothiol A and trypanothione, together with unique trypanothione-linked enzymes. Specific anaerobic protozoa possess another exclusively microbial enzyme, methionine gamma-lyase, which catabolises methionine (and homocysteine); the physiological significance of these non-mammalian activities is not fully understood. These unusual features offer opportunities for chemotherapeutic exploitation, and in some cases represent metabolic similarities with bacteria. Additionally, some anaerobic protozoa contain unidentified thiols and this implies the presence of further unusual enzymes/pathways in these organisms. So far, no truly unique targets for chemotherapy have been found in helminth sulphur amino acid metabolism, and to some degree this reflects the relative lack of detailed study in the area.

Amino Acids, Sulfur↗

Effect of Fasciola hepatica excretory-secretory products on the metabolic burst of sheep and human neutrophils.

F. hepatica excretory-secretory (ES) products were found to inhibit superoxide output in phorbol myristate acetate (PMA)-stimulated sheep and human neutrophils as measured by spectrophotometry. Luminol-enhanced chemiluminescence by PMA-stimulated neutrophils from both species was again inhibited. However, nitric oxide output by PMA-stimulated human neutrophils was significantly increased in the presence of ES products, whilst in sheep it was inhibited. No major effects were noted using resting neutrophils. The results are discussed in relation to the evolution of parasite defence mechanisms.

Animals↗

Routine preoperative "one-shot" intravenous pyelography is not indicated in all patients with penetrating abdominal trauma.

BACKGROUND: To determine which patients need a "one-shot" intravenous pyelogram (IVP) before laparotomy for penetrating abdominal trauma. STUDY DESIGN: Over a 15-month period, 240 laparotomies were performed for penetrating trauma at our urban level I trauma center. Prospectively collected data included clinical suspicion of genitourinary injury, results of preoperative IVP, intraoperative findings, and operative decisions influenced by the IVP. RESULTS: Preoperative IVP was performed in 175 patients (73%). Of these, 71 (41%) had suspicion of a renal injury based on the presence of a flank wound or gross hematuria. The IVP was believed to influence operative decisions in six patients, all in this group. Each of these six patients had either a shattered kidney or a renovascular injury and had a nephrectomy performed with the knowledge that a normal functioning kidney was present on the contralateral side. No patient without a flank wound or gross hematuria had an IVP that was judged to be helpful intraoperatively. Preoperative IVP was helpful only in patients with flank wounds or gross hematuria. Nephrectomy was performed in two additional patients who did not undergo IVP, both of whom presented in shock. CONCLUSIONS: Routine preoperative IVP is not necessary in all patients undergoing laparotomy for penetrating trauma. The number of IVPs can be safely reduced by 60% if the indications are narrowed to include only those stable patients with a flank wound or gross hematuria.

Abdominal Injuries↗

Anti-oxidant enzymes in Cryptosporidium parvum oocysts.

Oocysts of Cryptosporidium parvum showed relatively low levels of SOD activity. The SOD which had a pI of 4.8 and an approximate molecular weight of 35 kDa appeared to be iron dependent. Catalase, glutathione transferase, glutathione reductase and glutathione peroxidase activity could not be detected, nor could trypanothione reductase. No NADH or NADPH oxidase activity could be detected, nor could peroxidase activity be demonstrated using o-dianisidine, guaiacol, NADPH or NADH as co-substrates. However, an NADPH-dependent H2O2 scavenging system was detected in the insoluble fraction.

Animals↗

Electrophysiological analysis of the response of males of the potato cyst nematode, Globodera rostochiensis, to fractions of their homospecific sex pheromone.

Electrophysiological techniques and behavioural assays were used to determine the response of males of Globodera rostochiensis to 4 fractions of the homospecific sex pheromone from virgin females, separated using reverse-phase high-pressure liquid chromatography. Sex pheromone activity was confined to 2 of the fractions. The sex pheromone of G. rostochiensis appears to be composed of several weakly basic, polar compounds.

Animals↗

Ineffective esophageal motility (IEM): the primary finding in patients with nonspecific esophageal motility disorder.

Nonspecific esophageal motility disorder (NEMD) is a vague category used to include patients with poorly defined esophageal contraction abnormalities. The criteria include "ineffective" contraction waves, ie, peristaltic waves that are either of low amplitude or are not transmitted. The aim of this study was to identify the prevalence of ineffective esophageal motility (IEM) found during manometry testing and to evaluate esophageal acid exposure and esophageal acid clearance (EAC) in patients with IEM compared to those with other motility findings. We analyzed esophageal manometric tracings from 600 consecutive patients undergoing manometry in our laboratory following a specific protocol from April 1992 through October 1994 to identify the frequency of ineffective contractions and the percentages of other motility abnormalities present in patients meeting criteria for NEMD. Comparison of acid exposure and EAC was made with 150 patients who also had both esophageal manometry and pH-metry over the same time period. Sixty-one of 600 patients (10%) met the diagnostic criteria for NEMD. Sixty of 61 (98%) of these patients had IEM, defined by at least 30% ineffective contractions out of 10 wet swallows. Thirty-five of these patients also underwent ambulatory esophageal pH monitoring. Patients with IEM demonstrated significant increases in both recumbent median percentage of time of pH <4 (4.5%) and median distal EAC (4.2 min/episode) compared to those with normal motility (0.2%, 1 min/episode), diffuse esophageal spasm (0%, 0.6 min/episode), hypertensive LES (0%, 1.8 min/episode), and nutcracker esophagus (0.4% 1.6 min/episode). Recumbent acid exposure in IEM did not differ significantly from that in patients with systemic scleroderma (SSc) for either variable (5.4%, 4.2 min/episode). We propose that IEM is a more appropriate term and should replace NEMD, giving it a more specific manometric identity. IEM patients demonstrate a distinctive recumbent reflux pattern, similar to that seen in patients with SSc. This finding indicates that there is an association between IEM and recumbent GER. Whether IEM is the cause or the effect of increased esophageal acid exposure remains to be determined.

Adult↗

A method of determining peritoneal penetration in gunshot wounds to the abdomen.

BACKGROUND: It has previously been shown that 98% of gunshot wounds that penetrate the peritoneal cavity cause injuries that require surgical repair. Many gunshot wounds in the vicinity of the abdomen (GSWA) may actually be tangential and not penetrate the peritoneal cavity at all. Patients with such wounds may not require laparotomy. It is important to determine which patients with a potential tangential GSWA actually have penetration of the peritoneal cavity to minimize negative laparotomies. This study was undertaken to determine the sensitivity, specificity, and accuracy of diagnostic peritoneal lavage (DPL) in the determination of peritoneal penetration for patients who sustain GSWA. METHODS: DPL was performed for all patients who had sustained a GSWA in whom peritoneal penetration was unclear, i.e., patients whose GSWA appeared to be tangential, thoracoabdominal, or transpelvic and for whom a clear indication for laparotomy (shock, peritonitis, etc.) did not exist. Our threshold for a positive DPL was 10,000 red blood cells (RBC)/mm3. A prospective data base was kept with information on the location of the wound, DPL result, findings at laparotomy, and outcome. RESULTS: During a 4-year period, 429 consecutive DPLs were performed for GSWA at our urban Level I trauma center. One hundred fifty DPLs were positive, with more than 10,000 RBC/mm3. Six of these patients were found to have no peritoneal penetration at laparotomy (false-positive). The remaining 144 patients with positive DPLs were found to have operative injuries (true-positive). Of the 279 patients with DPL counts less than 10,000 RBC/mm3, 2 developed indications for laparotomy and were found to have intraperitoneal injuries (false-negative). The remaining 277 patients had no peritoneal injuries (true-negative). This was demonstrated either by laparotomy done for another indication (n = 7) or by uneventful inpatient observation for 24 hours (n = 270). The sensitivity, specificity, and accuracy of DPL in determining peritoneal penetration in GSWA is therefore 99, 98, and 98%, respectively. CONCLUSION: For patients who sustain GSWA for whom peritoneal penetration is unclear, DPL is a sensitive, specific, and accurate test to determine the need for laparotomy. It remains our test of choice when confronted with these patients.

Abdominal Injuries↗

The allogeneic CD4+ T-cell-mediated graft-versus-leukemia effect.

CD4+ T-cells have emerged as important cells in the initiation and delivery of the GVL response. Nevertheless it seems likely that they act in concert with other T-cells and NK cell effectors to produce the full in vivo effect of GVL. How they interact with other effectors is yet to be determined. Furthermore it is very likely that different hematological malignancies have different susceptibility to attack by various lymphocyte subsets, depending upon their MHC expression, nature of the antigens presented and other properties not yet defined. Here we specifically focus on the role of CD4+ T-cells in mediating GVL, particularly in chronic myeloid leukemia. Candidate antigens recognised by CD4+ cells are described and new approaches to GVL modulation in clinical bone marrow transplantation are discussed.

Bone Marrow Transplantation↗