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Biomedical subjects

J Webb

Publications and source records attributed to J Webb.

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

Biospeciation, by potentiometry and computer simulation, of Sm-EDTMP, a bone tumor palliative agent.

153Sm-EDTMP (ethylenediaminetetra(methylenephosphonic) acid) is of considerable interest as a bone therapeutic radiopharmaceutical but its properties in solution are not yet well characterized. The protonation constants of EDTMP and the formation constants of the complexes of Sm-EDTMP have accordingly been measured potentiometrically by glass electrode titrations at 25 degrees C in 0.15 M NaCl. Six protonation constants (log beta 011 = 9.638, log beta 012 = 17.330, log beta 013 = 23.597, 10g beta 014 = 28.636, log beta 015 = 31.501, log beta 016 = 32.624) and the formation constants of the [Sm(EDTMP)H-1]6-(log beta 11-1 = 4.865), [SmEDTMP]5-(log beta 110 = 12.018), [Sm(EDTMP)H]4- (log beta 111 = 17.892) and [Sm(EDTMP)H2]3- (log beta 112 = 23.437) complexes were determined. Computer simulations indicate that the [SmEDTMP]5- and the hydroxy [Sm(EDTMP)H-1]6- species are the major Sm(III) complexes formed in blood plasma, which explains the high degree of localization in the kidney and urine observed in biodistribution studies. Calcium ions are probably the major competitor for EDTMP in blood plasma. As the presence of secondary skeletal metastases results in a high rate of bone turnover, it is possible that the high concentration of calcium at these sites encourages localization of 153Sm-EDTMP.

Bone Neoplasms↗
PubMed1996

Manual assessment of fracture stiffness.

A fracture stiffness of 15 Nm/degree measured biomechanically has been proposed as a reliable indicator of early fracture union. This study used a fracture model to examine the ability of orthopaedic surgeons to assess the stiffness of a fracture manually. Twenty orthopaedic surgeons were tested along with 20 controls. They each estimated the stiffness of seven rods representing mid-shaft diaphyseal fractures at different stages of healing, and were asked whether the stiffness suggested that union had progressed to the stage where the stabilizing device could be removed. Surgeons were unable to estimate the fracture stiffness accurately, and greatly overestimated rod stiffness particularly for the lower values. This meant that on 83 per cent of occasions when the stiffness was less than 15 Nm/degree, the surgeons considered the fracture models united to a sufficient degree to prescribe removal of the fixator. The results suggest that clinical assessment of fracture stiffness alone may put 83 per cent of patients at risk of refracture or malunion. Manual testing of the mechanical stability of a fracture appears not to be reliable.

Biomechanical Phenomena↗
PubMed1996

Pharmaceutical evaluation of new drug submissions for metered-dose inhalers--Canadian style.

New proposals for the testing of dose delivery from metered-dose inhalers (MDI's) are discussed. Data are presented to show that overdosing may be a problem the first time an inhaler is used. Delivery of amounts of drug in excess of 2-3 times the label claim was observed for the first spray in one product. The problem was less severe for a second product but was still present. Dose delivery problems remain after initial use of the MDI's studied but underdosing was observed. The severity of the problem depends on the product and on a number of factors, including valve orientation during periods of inactivity and whether an unprimed or a primed spray is examined. Testing protocols and requirements that would be appropriate during product development and for quality control are discussed.

Administration, Inhalation↗
PubMed1996

Preliminary observations on possible premalignant changes in bone marrow adjacent to worn total hip arthroplasty implants.

Previous epidemiologic studies have suggested that there may be a risk of malignancy, especially lymphoma and leukemia, after joint replacement, but the followup has been relatively short. This is a preliminary study to see if there is any biologic basis for such a risk. Blood and bone marrow samples from 71 patients at revision arthroplasty of a loose or worn prosthesis and 30 control patients at primary arthroplasty were analyzed with cytogenetic techniques and molecular biology. There was a higher chromosomal aberration rate in cells adjacent to the prosthesis at revision surgery compared with iliac crest marrow from the same patients or with femoral bone marrow at primary arthroplasty. Clonal expansion of lymphocytes without a serum paraprotein was seen in 2 of 21 patients at revision arthroplasty performed more than 10 years after primary arthroplasty. The results of this preliminary study suggest that future epidemiologic studies should concentrate on patients with longer postoperative intervals to see if there is any risk that would be pertinent to a young patient at primary arthroplasty.

Aged↗
PubMed1996

Effects of a partial agonist and a full antagonist acting at the glycine site of the NMDA receptor on inflammation-induced mechanical hyperalgesia in rats.

1. NMDA receptor antagonists have previously been shown to have antinociceptive effects in behavioural experiments, but controversy remains as to the role of NMDA receptors in mechanical hyperalgesia. We have studied the effects on mechanical nociceptive thresholds in rats with carrageenin-induced paw inflammation of L-687,414, a low efficacy partial agonist which acts as a functional antagonist at the glycine modulatory site of the NMDA receptor and of L-701,324, a structurally novel, highly selective, full antagonist at this site. 2. Mechanical thresholds were measured for both hind paws 1 h before and 3 h after carrageenin or saline was injected into 1 hind paw. Dose-response curves were constructed for each test compound in separate experiments, with test compound or vehicle being given i.p. 1 h before the final test. 3. Both compounds produced selective dose-dependent and statistically significant reversal of mechanical hyperalgesia, with minimum effective doses of 100 mg kg-1 L-687,414 and 3 mg kg-1 L-701,324. Neither L-687,414 nor L-701,324 affected the response threshold of the contralateral non-inflamed paw over the dose-range producing reversal of carrageenin-induced hyperalgesia. Neither compound had any effect on the paw oedema produced by carrageenin injection. 4. These results show that both a full antagonist and a low efficacy partial agonist at the glycine modulatory site of the NMDA receptor complex reverse inflammation-induced mechanical hyperalgesia, thus supporting the argument that maximal activation of the glycine site is required for transmission via NMDA receptors, and showing that NMDA receptor-mediated actions are important in mechanical hyperalgesia induced by inflammation.

Animals↗
PubMed1996

Reproductive toxicity and tissue concentrations of lindane in adult male rats.

1. The effects of lindane on the reproductive system and its concentration in different tissues were investigated. Groups were dosed orally with 6 mg lindane/kg for 5 days or with a single dose of 30 mg/kg body weight. 2. The results indicate that the number (mio) of spermatids counted in the testes of both treated groups 2 weeks after treatment were significantly reduced compared to the control rats. Effects on the number of sperms were observed in both treated groups, but significant differences were only revealed on those with 30 mg/kg. 3. The concentration (microgram/g tissue) of lindane in adipose tissue, liver, brain and testis was determined 24 h and 2 weeks after the last treatment. Lindane was detected in the testis of both groups 24 h and 2 weeks after the last treatment. 4. Histological investigation by electron microscopy revealed a pronounced ballooning of Sertoli cells accompanied by fragmentation or complete loss of organelles. 5. According to the result obtained, it is evident that lindane passes through the testis and exerts its toxic effect.

Adipose Tissue↗
PubMed1995

Purification, characterization, and cloning of a heme-binding protein (23 kDa) in rat liver cytosol.

A heme-binding protein (designated HBP23) has been purified from rat liver cytosol using heme-affinity chromatography and either reverse-phase high-performance liquid chromatography or sequential ion-exchange chromatography. The protein (23 kDa) binds heme with an affinity (Kd = 55 nM) higher than that of the abundant cytosolic heme-binding proteins, heme-binding protein (HBP)/liver fatty acid-binding protein (L-FABP) and the glutathione S-transferases (GSTs) (Kd = 100-200 nM). HBP23 is present in the cytosol of liver, kidney, spleen, small intestine, and heart, with the liver showing the highest content. A cDNA coding the 23-kDa protein was cloned using reverse transcription polymerase chain reaction with degenerative oligonucleotides derived from partial amino acid sequences. The cloned cDNA encoded 199 amino acids, and its amino acid sequence showed no homology to HBP/L-FABP, GSTs, or any other heme-binding proteins or hemeproteins. Homology search showed that HBP23 is highly homologous to mouse macrophage 23-kDa stress protein, which is inducible by oxidant stress in peritoneal macrophages [Ishii, T., Yamada, M., Sato, H., Matsue, M., Taketani, S., Nakayama, K., Sugita, Y., and Bannai, S. (1993) J. Biol. Chem. 268, 18633-18636]. Thioredoxin peroxidase as well as HBP23 and the mouse macrophage 23-kDa stress protein are members of the peroxiredoxin family, a recently recognized class of antioxidant proteins [Chae, H. Z., Chung, S. J., & Rhee, S. G. (1994) J. Biol. Chem. 269, 27670-27678]. An increase in HBP23 mRNA was observed in Hepa 1-6 cells after treatment with heme and cadmium and during liver regeneration after partial hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

The value of critical incident analysis as an educational tool and its relationship to experiential learning.

Experiential learning and teaching strategies designed to facilitate this, have become popular in nursing and midwifery education in recent years. It is advocated that such learning enables the development of knowledge, skills and attitudes grounded in practice through the use of reflection on action. One strategy that may be utilised by nursing/midwifery educators to develop reflective ability in both themselves and students is critical incident analysis. It is suggested that critical incident analysis has value and is appropriate for developing interpersonal skills and self-awareness. It is proposed that critical incident analysis is a valuable educational tool which enables nursing/midwifery students to draw on past experiences and make sense of them, not only facilitating learning from clinical practice but also going some way towards bridging the gap between theory and practice.

Education, Nursing↗
PubMed1995

Characterization of a ubiquitinated protein which is externally located in African swine fever virions.

An antiserum was raised against the African swine fever virus (ASFV)-encoded ubiquitin-conjugating enzyme (UBCv1) and used to demonstrate by Western blotting (immunoblotting) and immunofluorescence that the enzyme is present in purified extracellular virions, is expressed both early and late after infection of cells with ASFV, and is cytoplasmically located. Antiubiquitin serum was used to identify novel ubiquitin conjugates present during ASFV infections. This antiserum stained virus factories late after infection, suggesting that virion proteins may be ubiquitinated. This possibility was confirmed by Western blotting, which identified three major antiubiquitin-immunoreactive proteins with molecular masses of 5, 18, and 58 kDa in purified extracellular virions. The 18-kDa protein was solubilized from virions at relatively low concentrations of the detergent n-octyl-beta-D-glucopyranoside, indicating that it is externally located and is possibly in the virus capsid. The 18-kDa protein was purified, and N-terminal amino acid sequencing confirmed that the protein was ubiquitinated and was ASFV encoded. The ASFV gene encoding this protein (PIG1) was sequenced, and the encoded protein expressed in an Escherichia coli expression vector. Recombinant PIG1 was ubiquitinated in the presence of E. coli expressed UBCv1 in vitro. These results suggest that PIG1 may be a substrate for UBCv1. The predicted molecular masses of the PIG1 protein and recombinant ubiquitinated protein were larger than the 18-kDa molecular mass of the ubiquitinated protein present in virions. Therefore, during viral replication, a precursor protein may undergo limited proteolysis to generate the ubiquitinated 18-kDa protein.

African Swine Fever Virus↗
PubMed1995

Evaluation of myocardial infarction therapy at a Canadian tertiary referral hospital.

OBJECTIVE: To evaluate the appropriateness of acute and postmyocardial infarction (MI) treatment. DESIGN: A retrospective chart review. SETTING: Tertiary care teaching hospital. PATIENTS: All patients admitted with a potential MI or who experienced an MI during their hospital stay from November 18, 1991 to September 20, 1992. RESULTS: For acute treatment, thrombolytics, acetylsalicylic acid (ASA) and intravenous beta-blockers were used in 82%, 96% and 39% of eligible patients with a median time delay of 1.4, 4.4 and 1.8 h, respectively. For post-MI treatment, ASA, oral beta-blockers, warfarin and angiotensin-converting enzyme inhibitors were used in 93%, 68%, 50% and 71% of eligible patients, respectively. CONCLUSIONS: ASA use was considered acceptable while the other therapies were underused. The time delays in the initiation of therapies were also considered longer than desirable. Ongoing audit may aid in improving the quality of care in future patients with an MI.

Adrenergic beta-Antagonists↗
PubMed1994

Antinociceptive and toxic effects of (+)-epibatidine oxalate attributable to nicotinic agonist activity.

1. Epibatidine is an analgesic substance, isolated from the skin of the poisonous frog Epipedobates tricolor, for which the mechanism of action was previously unknown. 2. The IC50 of synthetic (+)-epibatidine oxalate (the naturally occurring isomer) for [3H]-nicotine binding to rat whole-brain membranes was 0.1 nM. The (-)-isomer also exhibited high affinity (IC50 = 0.2 nM). 3. (+)- and (-)-Epibatidine exhibited much lower affinity for displacement of the muscarinic ligand [3H]-N-methylscopolamine binding to rat cortical membranes (Kapp = 6.9 microM and 16.0 microM respectively). The (+)-enantiomer of epibatidine had an antagonist/agonist (NMS/oxo-M) binding ratio of 4.2 This is consistent with a muscarinic antagonist profile. 4. (+)-Epibatidine oxalate (10 microM) did not cause significant (> 30%) displacement of radioligand binding to opioid, excitatory amino acid, benzodiazepine, 5-HT, dopamine, adrenaline or peptide receptors. 5. (+)- and (-)-Epibatidine (5-20 micrograms kg-1 s.c.) doubled response latency in the mouse hot-plate test. Antinociception and behavioural depression induced by (+)-epibatidine (5 micrograms kg-1) was fully blocked by the nicotinic antagonists mecamylamine (2 mg kg-1 s.c.) or dihydro-beta-erythroidine (2 mg kg-1 s.c.). The muscarinic antagonist scopolamine (0.4 and 10 mg kg-1 s.c.) caused partial reversal of antinociception induced by (+)-epibatidine in mice, but not in rats. 6. These findings demonstrate that (+)-epibatidine oxalate salt is a highly selective and potent nicotinic analgesic agent.

Analgesics↗
PubMed1994

Angioplasty of large diameter coronary arteries and saphenous vein grafts utilizing modified appropriately large diameter balloon dilatation catheters.

Standard coronary angioplasty balloons have generally not been available in diameters exceeding 4 mm. Consequently angioplasty of larger arteries and grafts is commonly performed with undersized balloons. "Hugging balloon" techniques and the use of peripheral angioplasty balloons introduced without a guiding catheter have been advocated. We utilized oversized (4.5--6.0-mm diameter) modified angioplasty balloons to perform angioplasty in 20 patients with large coronary arteries and saphenous vein grafts. Oversize balloons were used in conjunction with otherwise standard coronary angioplasty equipment and intracoronary stents.

Adult↗
PubMed1994

Diagnostic evaluation of short children with height 3 SD or more below the mean.

Most children who are more than 2 SD below the mean in height (less than third percentile) have no definable cause and are considered short-normal, but for children who are 3 SD below the mean (the lowest 0.13%), the prevalence of organic disease is known to be considerably greater. To better define the frequency of different diagnoses in this subgroup and to identify useful clinical findings, we reviewed the charts of all children referred for growth evaluation over a 10-year period who were > or = -3 SD in height, > 2 years old, and prepubertal. Of 60 patients (36 males and 24 females), 22% had constitutional growth delay (CGD), 23% had growth hormone deficiency (GHD), 13% had Turner syndrome, and 22% had various forms of primary growth failure (mostly associated with intrauterine growth retardation). Eight percent had very slow growth over a prolonged period but no definable cause, and 12% did not fall into any of the above groups. For differentiating GHD from CGD, a subnormal height velocity for age during a 4- to 12-month observation period, a low insulin-like growth factor-1/somatomedin C (IGF-1/Sm-C), and low total or free T4, with normal TSH, were all highly predictive of a diagnosis of GHD.

Body Height↗