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Biomedical subjects

J Ferguson

Publications and source records attributed to J Ferguson.

At least 145 records · Page 8Linked to original sources
PubMed1996

Pharmacological and neurochemical differences between acute and tardive vacuous chewing movements induced by haloperidol.

Late onset vacuous chewing movements (VCMs) from chronic neuroleptic treatment have been used as a rat model of tardive dyskinesia (TD). Early onset VCMs have also been observed, raising questions about the validity of this model. To assess the relationship between these two types of VCMs, pharmacological and neurochemical properties of early and late onset VCMs were compared. "Acute" VCMs were induced by daily intraperitoneal injections for 1-21 days. "Tardive" VCMs were induced by intramuscular injections of haloperidol decanoate every 3 weeks for 30 weeks followed by a 24-week withdrawal period. Suppression was attempted for both types of VCMs using several doses of intraperitoneal haloperidol. Striatonigral activation was assessed by measuring mRNA expression levels of the neuropeptides dynorphin and substance P using in situ hybridization histochemistry. Enkephalin mRNA was also measured as an index of striatopallidal activation. The results indicate that acute VCMs cannot be suppressed with increased doses of haloperidol and are associated with reduced dynorphin and substance P. This profile is similar to that seen with an animal model of parkinsonism. Tardive VCMs, in contrast, were markedly suppressed by haloperidol. They have previously been shown to be associated with increased striatonigral activation as indicated by increased dynorphin mRNA. Enkephalin mRNA was elevated following both short and long term treatment. Although superficially similar, acute and tardive VCMs appear to have different pharmacological and neurochemical profiles, suggesting they are related to acute extrapyramidal side effects and tardive dyskinesia, respectively.

Animals↗
PubMed1996

Effects of rating parameters on assessment of neuroleptic-induced vacuous chewing movements.

Long-term administration of neuroleptics to rats produces a syndrome of vacuous chewing movements (VCMs). The validity of the VCM syndrome as a model for tardive dyskinesia (TD) in humans is unclear. This is due, in part, to inconsistencies between studies. Methods for rating VCMs have varied markedly and could account for the inconsistencies. The purpose of this study was to evaluate the importance of the different methods on VCM scores. The effects of habituation and length of rating sessions were examined in rats habituated for 2 min, 1 h, or several hours over 4 days, compared to unhabituated rats. Ratings with and without habituation were highly correlated, as were ratings from 2- and 5-min observation periods. Ratings from neuroleptic-treated rats in restraining tubes, however, were significantly correlated with unrestrained ratings only following several hours of habituation. Locomotor activity was not correlated with VCM scores. These results suggest that habituation to open cages is not an important factor in assessing VCMs. Use of restraining tubes, however, may alter scores. The lack of an habituation effect or of a relationship between activity and VCMs suggests that locomotor and oral behaviors are not necessarily in competition. Restraining rats to rate VCMs does not appear to be necessary and could alter the neurobiology of VCMs.

Animals↗
PubMed1996

Myocardial infarction patients in the 1990s--their risk factors, stratification and survival in Canada: the Canadian Assessment of Myocardial Infarction (CAMI) Study.

OBJECTIVES: This study sought to evaluate the in-hospital and postdischarge mortality of patients with an acute myocardial infarction in the 1990s. BACKGROUND: The widespread implementation of therapeutic interventions that modify the natural history of coronary artery disease has led to changes in the profile and survival of patients with an acute myocardial infarction. Although data exist for selected subsets of patients with an acute myocardial infarction, at this time there is little recent prospective information on all patients presenting with an acute myocardial infarction, particularly for survival after hospital discharge. METHODS: All patients < or = 75 years old presenting with an acute myocardial infarction between July 1, 1990 and June 30, 1992 at nine Canadian hospitals were prospectively evaluated and followed up for 1 year. From November 1991, patients of all ages were included. In two centers, recruitment continued until December 31, 1992. A total of 3,178 patients were recruited. RESULTS: The in-hospital mortality rate of patients < or = 75 years old was 8.4%, and that at 1 year after hospital discharge was 5.3%. For patients of all ages recruited after November 1, 1991, the in-hospital mortality rate was 9.9% and 7.1% for 1 year after hospital discharge. For patients < or = 75 years old, age carried an independent in-hospital but no post discharge risk. Female patients had a twofold greater risk of dying in hospital. After hospital discharge, only 1.7% of patients < or = 75 years old and 1.9% of patients of all ages died of a presumed arrhythmic death. Premature ventricular contractions had no independent prognostic value. The relatively low in-hospital (5.3%) and postdischarge (6.1%) reinfarction rate may have contributed to improved survival. A greater reinfarction rate in patients >75 years old (17.4% vs. 9.6%, p < 0.001) may have contributed to their poorer outcome. CONCLUSIONS: One-year mortality after acute myocardial infarction continues to decrease, and changes in the prognostic value of traditional methods of risk stratification have occurred.

Age Factors↗
PubMed1996

Hepatitis C virus: epidemiology and genotypes in the north east of England.

The epidemiology of hepatitis C virus (HCV) infection was studied in an English teaching hospital over an 18 month period. A total of 104 HCV antibody positive patients were referred for further investigation. They were divided into those diagnosed through screening (blood donors and intravenous drug abusers) and those diagnosed for other reasons, and their mean ages, known risk factors for HCV transmission, genotypes, and liver biopsy histology were analysed. Screened patients were significantly younger than the others. No significant difference in age was found between genotypes. Most patients genotyped (69%) were genotype 1. Intravenous drug abusers had a higher proportion of subtype 1a, and patients who acquired HCV through blood transfusion had a higher proportion of subtype 1b. Liver biopsy specimens were scored using a histological activity index for liver inflammation and fibrosis. Patients with subtype 1b had significantly more severe liver disease than other genotypes when the histological activity index scores for fibrosis were analysed (p < 0.05). Liver disease worsened significantly with age according to all three histological activity index scores (portal activity: p < 0.01, acinar activity: p < 0.001, fibrosis: p < 0.0001). Liver disease worsened with increased duration of infection (p < 0.002), and patients who also abused alcohol presented at a significantly younger age (cirrhosis, p < 0.05, hepatocellular carcinoma, p < 0.02).

Adult↗
PubMed1996

Clinically suspected scaphoid fracture: a comparison of magnetic resonance imaging and bone scintigraphy.

59 patients with clinical suspicion of scaphoid fracture, but negative radiographs at presentation and review, were examined by magnetic resonance imaging (MRI) and bone scintigraphy (BS). The diagnoses were compared with subsequent follow-up. There were four scaphoid fractures, 10 other fractures and three significant ligamentous injuries. All scaphoid fractures were identified by MRI and BS. MRI showed better interobserver agreement for scaphoid injury than BS and fewer false positive reports. Significant ligamentous injury and carpal instability diagnosed by MRI were not evident on scintigraphy. Using fast scanning protocols, the cost of MRI is comparable with that of BS. MRI should be considered as the appropriate second line investigation in these clinical circumstances.

Adolescent↗
PubMed1996

Plasma exchange therapy for solar urticaria.

We report two cases of severe idiopathic solar urticaria treated with plasma exchange therapy. Previous treatment which included antihistamines and, in one patient, desensitization with psoralens and ultraviolet A (PUVA) and narrowband ultraviolet B phototherapy produced only partial benefit. The effect of plasma exchange therapy was assessed using monochromator phototesting and intradermal injection of in vitro irradiated serum. One patient responded but relapsed within 2 weeks. We have failed to demonstrate a lasting benefit from plasma exchange therapy (PExT) in the treatment of two patients with idiopathic solar urticaria.

Adult↗
PubMed1996

8-MOP PUVA for psoriasis: a comparison of a minimal phototoxic dose-based regimen with a skin-type approach.

Two ultraviolet A (UVA) regimens for oral 8-methoxypsoralen (8-MOP) photochemotherapy (PUVA) for moderate/severe chronic plaque psoriasis using a half body study technique were compared. Each patient received both regimens. A higher-dose regimen based on minimal phototoxic dose (MPD) with percentage incremental increases was given to one-half of the body. The other half received a lower dose regimen based on skin type with fixed incremental UVA increases. Patients were treated twice weekly. Symmetrical plaques were scored to determine the rate of resolution with each regimen. In addition, the number of treatments, cumulative UVA dose and number of days in treatment to achieve overall clearance were recorded. Patients were reviewed monthly for 1 year to record remission data. Thirty-three patients completed the study. Both regimens were effective and well tolerated. With the MPD-based approach, the number of exposures was significantly less for patients with skin types I and II but not III. Although the cumulative UVA dose was higher with the MPD regimen for all skin types studied, the reduced number of exposures required for clearance for skin types I and II but not III, combined with the security of individualized MPD testing, has practical attractions. MPD testing also identified five patients who required an increased psoralen dose and six patients who required a reduction of the initial UVA dose with the skin type regimen. Forty-two percent were still clear 1 year after treatment and there was no significant difference in the number of days in remission between the regimens for those whose psoriasis had recurred. The reduction in the number of exposures required for clearance with the MPD-based regimen may be safer and more cost effective in the long term.

Adult↗
PubMed1995

Loligomers: design of de novo peptide-based intracellular vehicles.

Defined branched peptides (loligomers) incorporating cytoplasmic translocation signals, nuclear localization sequences, and fluorescent probes were designed and synthesized to demonstrate the feasibility and simplicity of creating novel classes of intracellular vehicles. Loligomers containing all the above signals were rapidly internalized by Chinese hamster ovary (CHO) cells and accumulated in their nucleus. At 4 degrees C, the interaction of peptide constructs with CHO cells was limited to membrane association. Loligomers entered cells at higher temperatures by adsorptive endocytosis. Inhibitors of ATP synthesis affected cytoplasmic import only weakly but abolished nuclear uptake. The peptide signals guided both cytoplasmic and nuclear localization events. The properties exhibited by loligomers suggest a strategy for the facile design of "guided" classes of intracellular agents.

Amino Acid Sequence↗
PubMed1995

The phototumorigenic potential of broad-band (270-350 nm) and narrow-band (311-313 nm) phototherapy sources cannot be predicted by their edematogenic potential in hairless mouse skin.

The new Philips TL01 narrow-band (311-313 nm) and conventional broad-band (e.g., Philips TL12; 270-350 nm) sources are effective for psoriasis phototherapy, for which treatment regimens are based on a predetermined minimal erythema dose. TL01 phototherapy treatment times are approximately half those with TL12 for psoriasis, whereas the cumulative exposure doses at clearing are similar. We compared the phototumorigenic potential of TL01 and TL12 radiation in mouse skin. Groups of albino Skh-1 hairless mice were exposed for 5 d/week at three dose levels. At each dose level, TL12 and TL01 doses were equally edematogenic. At each dose level, TL01 radiation was significantly more effective at producing first tumors of 1 mm in diameter and multiple tumors. At the lower two dose levels, TL01 radiation produced a significantly greater proportion of squamous cell carcinomas. This study demonstrates that TL01 radiation is more phototumorigenic than TL12 radiation at equally edematogenically weighted doses. This is in contrast with previous reports that edema production by polychromatic sources is predictive of their phototumorigenic effect in Skh-1 mice. The absolute cumulative TL12 dose needed to induce tumors was much less than that for TL01 radiation. The possibility of increased tumor risk with TL01 phototherapy should be considered but must be balanced against the high phototherapeutic efficacy of this source, short treatment times, and the low cumulative doses necessary for clearing of psoriasis.

Animals↗
PubMed1995

Lack of photosensitising potential of tenidap, a novel anti-rheumatic agent.

1. The potential of orally administered tenidap sodium, a novel anti-rheumatic agent under investigation for the treatment of rheumatoid arthritis and osteoarthritis, to cause phototoxic reactions was investigated. 2. Twenty-four healthy volunteers entered a randomised, double-blind study in which they received tenidap sodium 40 mg or 120 mg or placebo daily for 7 days. The minimal erythema dose was determined using wavelengths of 305-460 nm for 3 days prior to drug administration and on the last 3 days of dosing. Appropriate clinical and laboratory tests were performed before, during and after the dosing period. 3. Tenidap did not have a statistically significant effect on immediate or delayed photosensitivity. No drug-related side effects were reported and there were no clinically significant adverse findings from the laboratory tests. 4. At the dosage and duration of tenidap sodium used, a photosensitising potential has not been demonstrated.

Adult↗
PubMed1995

Narrow-band UVB (TL-01) phototherapy: an effective preventative treatment for the photodermatoses.

Twenty patients with photodermatoses [actinic prurigo (n = 6), hydroa vacciniforme (n = 4), idiopathic solar urticaria (n = 1), amiodarone-induced photosensitivity (n = 1) and a range of cutaneous porphyrias (n = 8)] were treated with a 'hardening' course of narrow-band ultraviolet B (TL-01) phototherapy in springtime. The response to phototherapy was monitored subjectively, by interviewing patients after the summer, and objectively by monochromator phototesting, before and after phototherapy. Fifteen patients reported that treatment was worthwhile. Monochromator phototesting after phototherapy revealed a fourfold increase in the minimal erythema dose in those with abnormal photosensitivity to ultraviolet A wavebands. Adverse effects included erythema (seven patients), pruritus (five) and provocation of the eruption (four). We now routinely consider narrow-band UVB phototherapy for problem photodermatoses.

Adolescent↗
PubMed1995

Methods to assess RAST results in patients exposed to chemical allergens.

RAST is routinely used to assess the presence of IgE antibodies against environmental allergens in the sera of symptomatic patients. With exposure to low-mol.-mass (chemical) allergens, RAST is also done, but the interpretation of results is more difficult. A study was undertaken to assess methods which have been employed to determine the positivity of sera and to develop an objective, statistically based procedure for determination of RAST positivity to chemical allergens. Sera were obtained from 14 nonsensitized (control) subjects and examined for total IgE by radioimmunoassay, and for cyanuric chloride (CyCl)-specific IgE by RAST. Linear regression analysis revealed the correlation between the tests to be 0.94. Equations for the 95% and 99% predicted intervals were obtained. Sera from 19 cyanuric chloride workers were tested for total and specific IgE. Positivity of RAST results was determined by three methods: RAST inhibition, RAST ratio (binding to CyCl-human serum albumin (HSA) disks/HSA disks), and the regression equation where values outside the 99% predicted interval were considered to be positive and those > 95% < 99% were considered to be borderline values. Determination of CyCl RAST positivity by the regression method gave results comparable to those obtained from RAST inhibition, whereas the RAST ratio resulted in many more false positive conclusions. This statistical approach to RAST analysis was also used to assess sera from patients exposed to the unrelated chemical allergens, toluene diisocyanate and formaldehyde. Conclusions based on the regression method were in good agreement with those from RAST inhibition assay. Moreover, use of one standard curve may be sufficient for interpretation of RAST results for diverse haptenic allergens. These results indicate that the regression method provides a statistical basis from which to determine positivity of RAST analyses while eliminating the need for RAST inhibition assays.

Allergens↗