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Biomedical subjects

M Hunt

Publications and source records attributed to M Hunt.

At least 55 records · Page 3Linked to original sources
PubMed1996

Pitfalls of patient education. Limited success of a program for back pain in primary care.

STUDY DESIGN: Low back pain patients seen in primary care were allocated randomly to one of two educational interventions or to usual care. OBJECTIVE: To evaluate educational interventions designed to improve the outcomes of primary care for low back pain. SUMMARY OF BACKGROUND DATA: Patients with back pain are frequently dissatisfied with their medical care and identify lack of information as the most insufficient aspect. METHODS: In a large Health Maintenance Organization clinic, 293 subjects were allocated randomly to receive usual care, an educational booklet, or a 15-minute session with a clinic nurse, including the booklet and a follow-up telephone call. Outcome measures included satisfaction with care, perceived knowledge, participation in exercise, functional status, symptom relief, and health care use. Outcomes were assessed 1, 3, 7, and 52 weeks after the intervention. RESULTS: The nurse intervention resulted in higher patient satisfaction than usual care (P < 0.001) and higher perceived knowledge (P < 0.001). Self-reported exercise participation was also higher in the nurse intervention group after a 1-week follow-up period (97% vs. 65% in the other groups; P < 0.0001). There were no significant differences among the three groups in worry, symptoms, functional status, or health care use at any follow-up interval. Differences in self-reported exercise and perceived knowledge were no longer significant after 7 weeks. CONCLUSIONS: These findings challenge the value of purely educational approaches in reducing functional impact or health care use related to back pain and also challenge the value of fitness exercise in the most acute phase of back pain.

Adult↗
PubMed1996

Immunity and vaccine development in Pasteurella multocida infections.

The role of LPS in immunity was studied using monoclonal antibodies (MAbs) and active immunisation experiments. A panel of six MAbs produced against Pasteurella multocida serotype B:2 reacted with the LPS of serotypes B:2 and B:5, but not with other serotypes. The MAbs could opsonise P. multocida for phagocytosis by mouse macrophages, but were not bactericidal in the presence of complement. They conferred only partial passive protection in mice. Similar results showing only partial protection were obtained when purified LPS was used to actively immunise mice prior to challenge, suggesting that LPS plays a partial role in immunity to infection. The aroA gene from P. multocida serotypes A:1 and A:3 was cloned and inactivated by insertion of a kanamycin resistance gene. The mutated gene was re-introduced onto the chromosome by allelic exchange. The resultant aroA mutants were highly attenuated in a mouse model system, with a 6-log decrease in ID50. Virulence could be restored by complementation with a functional aroA gene. Mice immunised with two doses of the live mutants were protected against lethal challenge with the homologous parental strain, but not against the heterologous strain. P. multocida A:1 and A:3 expressed unique proteins when grown in iron-restricted medium. Moreover, the outer membrane (OM) fractions of these cells contained novel proteins of 75 kDa, 85 kDa and 94 kDa molecular mass. Mice were immunised with OM fractions prepared from serotype A:3 grown in iron-restricted (OM Fe-) or iron-replete (OM Fe+) media. When low challenge doses were used, both immunogens protected mice against serotype A:3, but only the OM Fe- fraction protected mice against heterologous challenge with serotype A:1. When higher challenge doses were used, only partial protection was observed.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1996

Deactivation of vascular endothelium by monoclonal anti-tumor necrosis factor alpha antibody in rheumatoid arthritis.

OBJECTIVE: To assess whether monoclonal antibody to tumor necrosis factor alpha (TNF alpha) reduces endothelial activation in rheumatoid arthritis (RA). METHODS: Levels of serum E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1), and circulating leukocytes (differential counts) were measured in RA patients before and up to 4 weeks after infusion of either placebo or chimeric anti-TNF alpha antibody cA2 (1 or 10 mg/kg). RESULTS: Treatment with anti-TNF alpha decreased serum E-selectin and ICAM-1 levels, with the earliest detectable changes observed on days 1-3 after anti-TNF alpha infusion. No effect on VCAM-1 levels was detected. In parallel, there was a rapid and sustained increase in circulating lymphocytes. The extent of the decrease in serum E-selectin and ICAM-1 levels and the increase in lymphocyte counts was significantly higher (P < or = 0.05) in patients in whom a clinical benefit of anti-TNF alpha was observed ( > or = 20% response, by Paulus criteria, at week 4) compared with that in patients who failed to respond to anti-TNF alpha at this time point. CONCLUSION: We propose that decreased serum levels of adhesion molecules may reflect diminished activation of endothelial cells in the synovial microvasculature, leading to reduced migration of leukocytes into synovial joints, and thus prolonging the therapeutic effect of anti-TNF alpha in RA.

Antibodies, Monoclonal↗
PubMed1996

The control of oral secretions in bulbar ALS/MND.

For the bulbar ALS/MND patient with dysphagia, the accumulation of oral secretions is a distressing problem. The control of these secretions, particularly the thick mucus form, is very difficult. In approaching this problem it is important to realise that the source of these secretions is not just from the oral salivary glands. The nose and lungs also contribute a constant flow of serous and particularly mucoid fluids. The neural control of these different forms of secretion is of importance in controlling them. Stimulation of cholinergic receptors produces thin serous secretions whereas beta adrenergic receptors produce thick protein and mucus-rich secretions. Therefore 16 bulbar ALS/MND patients were treated with beta antagonists after maximising other therapy. 75% of this group had fast and significant relief from their thick secretions. It is therefore proposed to perform a large controlled trial of beta blockers in the control of thick oral secretions in ALS/MND based on these promising pilot data.

Adrenergic beta-Antagonists↗
PubMed1996

Benzothiadiazole induces disease resistance in Arabidopsis by activation of the systemic acquired resistance signal transduction pathway.

Benzothiadiazole (BTH) is a novel chemical activator of disease resistance in tobacco, wheat and other important agricultural plants. In this report, it is shown that BTH works by activating SAR in Arabidopsis thaliana. BTH-treated plants were resistant to infection by turnip crinkle virus, Pseudomonas syringae pv 'tomato' DC3000 and Peronospora parasitica. Chemical treatment induced accumulation of mRNAs from the SAR-associated genes, PR-1, PR-2 and PR-5. BTH treatment induced both PR-1 mRNA accumulation and resistance against P. parasitica in the ethylene response mutants, etr1 and ein2, and in the methyl jasmonate-insensitive mutant, jar1, suggesting that BTH action is independent of these plant hormones. BTH treatment also induced both PR-1 mRNA accumulation and P. parasitica resistance in transgenic Arabidopsis plants expressing the nahG gene, suggesting that BTH action does not require salicylic acid accumulation. However, because BTH-treatment failed to induce either PR-1 mRNA accumulation or P. parasitica resistance in the non-inducible immunity mutant, nim1, it appears that BTH activates the SAR signal transduction pathway.

Arabidopsis↗
PubMed1996

Improving schizophrenic in-patients' Wisconsin card-sorting performance.

The effectiveness of a training procedure to improve schizophrenic patients' Wisconsin Card Sorting Test performance was investigated. In the absence of the monetary incentive often employed, 10 schizophrenic in-patients' performance improved with training. This study provides further evidence that the cognitive deficiency associated with the frontal lobe, implied by schizophrenic patients' typically poor Wisconsin Card-Sorting Test performance, is remediable.

Analysis of Variance↗
PubMed1996

Pain mechanisms in osteoarthritis of the knee: effect of intraarticular anesthetic.

OBJECTIVE: The causes of pain in osteoarthritis (OA) remain unclear. We examined the effect of intraarticular (IA) local anesthetic (LA) on pain perception in OA knee to test the hypothesis that pain arises from structures in contact with the intraarticular surface. The effect of intervention on one knee on perception of pain in the other was also studied. METHODS: Using a single blind, blind observer design, 20 subjects with bilateral symptomatic OA knee were randomized to receive either IA LA (bupivacaine 0.25%, 5 ml) or placebo into the most painful knee. Pain from both knees was assessed at 1 h, 24 h, and 7 days using a 100 mm visual analog scale (VAS). Pain descriptors using a standardized questionnaire (McGill) were recorded. RESULTS: At 1 h there was a significant fall in pain in LA knees (median VAS 61.5 to 0.0; p = 0.007). The change at VAS was significantly different between knees receiving LA and placebo (median change -45.5 vs +3.5; p = 0.03). 6/10 LA knees scored 0 on VAS at 1 h. Noninjected knees also showed a fall in pain scores. For knees contralateral to those receiving LA, the fall was from median 28.0 to 1.0 (p = 0.08). The reduction in pain was much less in knees contralateral to those receiving placebo (median 43.5 to 38.0), though the difference between the changes did not reach statistical significance. VAS scores remained below baseline for 7 days, though this difference was not significant. McGill pain scores fell in the LA group (for all categories of pain), but did not change in the placebo group. CONCLUSION: Pain in some cases of OA knee can be abolished by IA LA, suggesting that the structures responsible for pain are in contact with the intraarticular environment. As well, interventions in one knee have significant effects on pain perception in the contralateral knee.

Aged↗
PubMed1996

Children's understanding of the meaning and functions of verbal irony.

We investigated children's understanding of irony and sensitivity to irony's meanness and humor. In Study 1, 89 participants (5-6-year-olds, 8-9-year-olds, adults) heard ironic and literal criticisms, and literal compliments. Comprehension of irony emerged between 5 and 6 years of age. Ratings of humor increased with age; ratings of meanness did not (showing that all ages perceived irony as more muted than literal criticism). In Study 2, results from 135 participants (6-7-year-olds, 8-9-year-olds, and adults) replicated these findings and revealed the role of form and intonation. Thus, comprehension of irony emerges between 5 and 6 years of age, and sensitivity to the muting function develops prior to sensitivity to the humor function.

Age Factors↗
PubMed1995

Lith1, a major gene affecting cholesterol gallstone formation among inbred strains of mice.

The prevalence of cholesterol gallstones differs among inbred strains of mice fed a diet containing 15% (wt/wt) dairy fat, 1% (wt/wt) cholesterol, and 0.5% (wt/wt) cholic acid. Strains C57L, SWR, and A were notable for a high prevalence of cholelithiasis; strains C57BL/6, C3H, and SJL had an intermediate prevalence; and strains SM, AKR, and DBA/2 exhibited no cholelithiasis after consuming the diet for 18 weeks. Genetic analysis of the difference in gallstone prevalence rates between strains AKR and C57L was carried out by using the AKXL recombinant inbred strain set and (AKR x C57L)F1 x AKR backcross mice. Susceptibility to gallstone formation was found to be a dominant trait determined by at least two genes. A major gene, named Lith1, mapped to mouse chromosome 2. When examined after 6 weeks on the lithogenic diet, the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.88) was downregulated as expected in the gallstone-resistant strains, AKR and SJL, but this enzyme failed to downregulate in C57L and SWR, the gallstone-susceptible strains. This suggests that regulation of the rate-limiting enzyme in cholesterol biosynthesis may be pivotal in determining the occurrence and severity of cholesterol hypersecretion and hence lithogenicity of gallbladder bile. These studies indicate that genetic factors are critical in determining gallstone formation and that the genetic resources of the mouse model may permit these factors to be identified.

Animals↗
PubMed1995

Purification and characterization of phospho enol pyruvate carboxykinase from Trypanosoma brucei.

ATP-dependent phospho enol pyruvate carboxykinase (EC 4.1.1.49; PEPCK, ATP) was purified from glycosomes of cultured procyclic Trypanosoma brucei to electrophoretic homogeneity. The purified enzyme exhibited a mean specific activity of 83 units mg-1, as measured in the carboxylation direction at 30 degrees C. A similar activity was obtained for the decarboxylation reaction. The enzyme was shown to be a homodimer in solution with a subunit molecular mass of 59 kDa. Amino acid sequence analysis suggested that the PEPCK (ATP) is identical to the trypanosomal protein p60, the sequence of which was previously predicted from the corresponding nucleotide sequence by other investigators. The basic nature of the enzyme was indicated by a high isoelectric point (pH 8.9). The enzyme was found to be strictly dependent on adenosine nucleotides for activity, as well as on the presence of Mn2+. Mg2+ was found to be ineffective as activator of the trypanosomal enzyme, but a combination of subsaturating (< or = 300 microM) concentrations of Mn2+ and high concentrations of Mg2+ caused a synergistic effect on the carboxylation activity, indicating a dual cation requirement. Mn2+ is necessary to activate the enzyme and Mn2+ or Mg2+ most likely forms the cation-nucleotide complex as the active form of the substrate. Relatively high (5 mM) levels of ATP were required to produce a significant inhibition of the carboxylation reaction. Quinolinic acid, a structural analogue of oxaloacetate, completely inhibited the decarboxylation reaction at a 1 mM concentration. The apparent Michaelis constants of the enzyme were 490 microM for PEP, 37 microM for oxaloacetate, 40 microM for ADP, 10.3 microM for ATP, 970 microM for Mn2+ and 26 mM for HCO3-. Endogenous substrate concentrations were found to be 327 nmol PEP, 1486 nmol ADP, 4200 nmol ATP and 11.5 nmol Mn2+ (ml cell volume)-1. Our kinetic data suggest that under physiological conditions PEPCK (ATP) in T. brucei is bidirectional and that its activity is regulated primarily by mass action. The physiological relevance of the enzyme in procyclic T. brucei is discussed.

Amino Acid Sequence↗
PubMed1994

Effects of beam modifiers and immobilization devices on the dose in the build-up region.

PURPOSE: To analyze the effect that immobilization devices used in conjunction with beam modifiers may have on the dose to the skin and build-up region. METHODS AND MATERIALS: Central axis depth dose measurements were made in a polystyrene phantom in the build-up regions using the 6 and 15 MV photon beams, at two different source-to-phantom distances, and various field sizes. The effects of acrylic blocking trays, lead wedges, and cerrobend blocks were assessed in conjunction with the enhancement of dose in the build-up region due to immobilizing devices using plaster and thermoplastic casting materials of different thicknesses. RESULTS: For the 6 MV photons, solid (3 mm) thermoplastic casting material was found to have the greatest effect on surface dose: for a 12 x 12 cm field we measured 79% of maximum dose when treating through the material versus 22% of maximum dose when no beam modifiers or immobilization devices are used. Measurements were also made to evaluate the effect of the immobilization of patients receiving three-dimensional conformal treatments using a 15 MV photon beam. CONCLUSIONS: The relevance of these results to treatments in the pelvis, breast, and head and neck regions is discussed. For 6 MV beams, special consideration should be given if the need arises to treat through the immobilization device, as unacceptable skin reactions may result.

Dose-Response Relationship, Radiation↗
PubMed1994

Studies on compounds promoting the in vitro transformation of Trypanosoma brucei from bloodstream to procyclic forms.

In vitro differentiation of pleomorphic blood-stream forms of Trypanosoma brucei to procyclic culture forms occurred rapidly and at high rates at 27 degrees C in a culture medium containing 1 mM cis-aconitate as the transformation-inducing agent. Citrate was required at a much higher concentration (10 mM) to produce a similar transformation rate. The highest percentage of transformed cells was obtained when bloodstream-form trypanosomes were treated with pronase in the absence of a feeder-cell layer. However, under these conditions, the amount of procyclic forms obtained after 72 h was lower than that obtained in the presence of cis-aconitate. Trypsin was also capable of inducing transformation in the absence of a feeder-cell layer, but this treatment again resulted in low numbers of transformed cells. Blood-stream-form trypanosomes were incapable of taking up citrate to any significant extent and the citrate content of these stages was negligible. After 72 h of exposure to citrate (3 mM), intracellular levels of this compound remained very low (< 1 nmol (10(9) cells)-1), increasing in established procyclic stages to approximately 1.7 nmol (10(9) cells)-1. These observations suggest that the tricarboxylic acid (TCA)-cycle metabolite-dependent transformation may be initiated externally to the trypanosome cell membrane. The ability of both citrate and cis-aconitate to bind calcium and, thus, to reduce the concentration of this cation in the culture medium was found not to be responsible for the triggering effect on trypanosome transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aconitic Acid↗
PubMed1994

Recombinant human erythropoietin for the treatment of the anaemia associated with autologous bone marrow transplantation.

Patients with solid tumours undergoing high-dose chemotherapy with autologous bone marrow transplantation use an average of 10 units of packed red blood cells (PRBC) while awaiting haemopoietic reconstitution. They are also known to have inappropriately low endogenous erythropoietin levels for their degree of anaemia. This pilot study was designed to determine the effects of recombinant human erythropoietin (rHuEPO) on erythroid recovery and PRBC transfusion requirements. Ten patients received high-dose chemotherapy (days -7 to -3), bone marrow reinfusion (day 0), and then rHuEPO (day 1 onward). RHuEPO (200 units/kg intravenous bolus daily), along with iron supplementation, was administered for 28 d or until a haematocrit (Hct) of 35% (independent of transfusions) was reached, whichever occurred first. PRBCs were routinely given for Hct < or = 25% and platelets for counts < 20,000/microliters. Eight (80%) patients developed a brisk reticulocytosis (median peak reticulocyte count 0.32 x 10(9)/l) and a haematocrit > or = 30% independent of red blood cell transfusions within 32 d of receiving marrow, as compared to 20/37 (54%) similarly treated controls. An unexpected finding was the more rapid engraftment in myeloid and platelet lineages in a subset of rHuEPO-treated patients. Quick return of red blood cells (17 v 33 d) (P = 0.0001), platelets (14 v 19 d) (P = 0.04), and neutrophils (13 v 25 d) (P = 0.01) (with circulating myeloblasts and early myeloid forms) characterized recovery from an ifosfamide-based intensification with rHuEPO support. Similar trilineage enhancement of haemopoiesis did not occur with the possibly more myeloablative cyclophosphamide-based regimens. Despite the enhancement by rHuEPO on reticulocytosis, there was no significant decrease in PRBC transfusion requirements. RHuEPO proved to be a well-tolerated agent in enhancing reticulocytosis following high-dose chemotherapy. Further study to elucidate the activity of erythropoietin on both erythroid and non-erythroid growth and maturation appears warranted.

Adult↗
PubMed1994

Using the Delphi survey technique to develop a professional definition of nursing for analysing nursing workload.

This paper describes the use of the Delphi survey technique to develop a professional definition of nursing which is used as a framework for analysing the contribution made to care by learner nurses prior to the introduction of Project 2000. A detailed account is provided of the importance of generating a theoretical nursing perspective to structure the first round of the Delphi survey. The paper goes on to question the validity of developing a consensus about nursing priorities in subsequent rounds of the Delphi survey and argues instead that priorities about nursing care needs can only be determined in the context of practice.

Activities of Daily Living↗
PubMed1994

Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.

We have examined several aspects of neurotransmitter function in the brains of mice carrying a deletion mutation in the gene encoding the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). During the first 6 weeks of postnatal development, dopamine levels in whole-brain extracts from the mutant mice (HPRT-) failed to increase at rates comparable to normal animals, resulting in 40% lower dopamine levels throughout adulthood. Regional analysis in adult animals showed the caudoputamen to be the most severely affected region, with dopamine deficits of 48-64%. Dopamine levels in other regions were normal or less severely affected. The decrease in dopamine was accompanied by a decrease in tyrosine hydroxylase (TH) activity, the rate-limiting step in dopamine synthesis. Kinetic analysis of TH extracted from the caudoputamen of normal and HPRT- mice demonstrated a 45% decrease in Vmax with an increased affinity for the tetrahydropterin cofactor in the mutants. Labeling of midbrain dopamine neurons using TH immunohistochemistry revealed no obvious deficits in the number of midbrain dopamine neurons, but quantitative autoradiographic studies revealed significant reductions in the binding of 3H-N-[1-(2-benzo(beta)thiophenyl)cyclohexyl]piperidine (3H-BTCP) to dopamine uptake sites in the forebrain of the mutants. In contrast to these abnormalities of the dopamine systems in the mutant mice, other neurotransmitter systems appeared relatively unaffected. Norepinephrine, 5-HT, tryptophan hydroxylase, and glutamic acid decarboxylase were present at normal levels in the brains of the mutants. ChAT activity was slightly lower than normal in the caudoputamen of the mutant animals, but was normal in all other brain regions examined. These results indicate that HPRT deficiency is associated with a relatively specific deficit in basal ganglia dopamine systems that emerges during the first 2 months of postnatal development.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Intensive combined modality therapy for limited-stage small-cell lung cancer.

BACKGROUND: Conventional-dose chemotherapy for small-cell lung cancer has resulted in high response rates but rarely in a cure. The addition of thoracic radiotherapy (chemoradiotherapy) has improved survival for patients having limited disease, resulting in a median survival of 14-18 months. Previous trials evaluating high-dose chemotherapy and autologous bone marrow transplantation have demonstrated enhanced complete response rates without documenting overall survival benefit. PURPOSE: The purpose of this phase II trial was to determine the disease-free and overall survival, toxic effects, and relapse patterns in patients with limited small-cell lung cancer who were in partial or complete response to first-line conventional-dose chemotherapy and then received intensive systemic combined modality therapy. METHODS: Adults with stage III small-cell lung cancer who had achieved at least a partial response to conventional-dose induction chemotherapy were treated with high-dose cyclophosphamide, cisplatin, and carmustine combined with autologous bone marrow transplantation. Cumulative doses of the three drugs were 5625, 165, and 480 mg/m2, respectively. After recovery, patients received thoracic radiotherapy (50-60 Gy in 25-30 fractions over 5-6 weeks) and cranial radiotherapy (30 Gy in 15 fractions during 3 weeks). RESULTS: Of 19 patients in the study, six had achieved complete response, eight had a greater than 90% reduction in tumor size, and five had a 50%-90% reduction in tumor size. After high-dose therapy, 15 of the 19 were in complete response. Overall, median time to treatment failure after high-dose therapy was 12 months. Overall survival was 73% (95% confidence interval [CI] = 42%-89%) at 1 year and 53% (95% CI = 22%-77%) at 2 years. Of the 14 patients in or near complete response before high-dose therapy, 10 remain disease free with no further chemotherapy a median of 15 (4-69+) months after therapy. Actuarial 2-year disease-free survival is 57% (95% CI = 20%-82%). One patient died of Candida sepsis. Morbidity was low, and most patients returned to full-time work. With the exception of herpes zoster, there were no complications more than 3 months after high-dose therapy. CONCLUSIONS: The majority of the patients in this study are experiencing prolonged and unmaintained disease-free survival. Our findings suggest that patients in or near complete response before high-dose therapy have the most favorable prognosis. IMPLICATIONS: A randomized comparison between this approach and conventional-dose therapy is planned to define the utility of dose intensification with autologous bone marrow transplantation in the treatment of patients with limited-stage small-cell lung cancer who are in or near complete response.

Actuarial Analysis↗