Biomedical subjects
C MacDonald
Publications and source records attributed to C MacDonald.
Prevalence of posttraumatic stress disorder, depression and anxiety in a community sample of New Zealand Vietnam War veterans.
OBJECTIVE: The aim of the paper is to investigate the prevalence of posttraumatic stress disorder (PTSD), depression and anxiety in a community sample of New Zealand Vietnam War veterans. METHOD: Data were collected as part of a national survey on the health and mental health of New Zealand Vietnam veterans. Five hundred and seventy-three randomly selected male Vietnam veterans participated in a postal survey. The questionnaire contained a number of demographic, biographical and psychological measures. RESULTS: The results revealed that 10% of the veterans could be classified as PTSD cases and that these veterans exhibited high levels of depression and anxiety. In PTSD cases, 15% were also classified with anxiety, 6% with depression, and 73% were classified with both anxiety and depression. In PTSD cases 94% were classified with more than one additional disorder. In non-PTSD cases 27% were classified with anxiety, and 1% with depression, while 12% experienced both anxiety and depression. CONCLUSIONS: The consequences of comorbidity for research and treatment are discussed and it is suggested that health professionals should be attentive to military experience as a predictor of these disorders.
Interactions of orthopaedic metals with an immortalized rat osteoblast cell line.
The toxicity of nickel, chromium (III) and (VI), vanadium and aluminium was compared in an immortalized neonatal rat osteoblast cell line using the MTT assay and a novel index of cytotoxicity, alkaline phosphatase (ALP) activity. Where toxicity was observed, ALP was a consistently more sensitive detection method than the MTT assay. The toxicity of the metals increased in the order aluminium < chromium (III) < vanadium < nickel < chromium (VI). alpha-Tocopherol partially prevented nickel-induced toxicity (as assessed by ALP activity), whereas ascorbic acid had no protective effect. Chromium (VI) was more toxic than (III), with significant toxicity observed at 0.5 microM. It is thought that Cr (III) cannot readily penetrate the cell membrane and this may account for the lower toxicity. Aluminium had a stimulatory effect on cell growth at low concentrations (0.5 microM). The combination of immortalized rat osteoblasts and the ALP activity test provides a powerful tool for in vitro testing of orthopaedic materials.
In vitro biocompatibility testing of polymers for orthopaedic implants using cultured fibroblasts and osteoblasts.
The biocompatibility of two polymers for potential use as orthopaedic implant materials in an isoelastic hip prosthesis was investigated. The interactions of polyetheretherketone (PEEK) and epoxy resin polymers (with and without carbon fibre reinforcement) with both fibroblasts and osteoblasts were tested using cell protein, intracellular reduced glutathione (GSH), leakage of lactate dehydrogenase and the MTT assay as indices of cellular cytotoxicity. The epoxy resin polymer was slightly cytotoxic to and inhibited the growth rate of fibroblasts (as assessed by total cell protein), and depleted GSH in both cell types. In contrast, the PEEK material did not display overt signs of cytotoxicity and, in fact, increased osteoblast cell protein content. This suggests that, of these two materials, PEEK would be the one of choice for development of an isoelastic implant and, in view of its stimulatory effect on osteoblast protein content, it may encourage ingrowth of bone around the prosthesis and thus minimize joint loosening.
Nurse in profile. Interview by Peter Schwab.
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Establishment and characterization of murine macrophage-like cell lines following transformation with simian virus 40 DNA deleted at the origin of replication.
Differentiated mammalian cell lines can be established by introducing viral oncogenes into primary cells. Such lines can retain their original specialised functions while being adapted to prolonged life in culture; but most transformed cell lines obtained in this way characteristically show altered properties compared with the primary cells. The result of these changes is that transformed cell lines no longer provide a good model of the original tissue, and indeed often resemble other transformed lines more than the initial cell type. In our laboratory three murine peritoneal macrophage-like cell lines have been isolated by transforming primary cells with SV40 origin-deleted DNA. These lines have been in continuous culture for approximately 1 year and have been shown to express many macrophage-specific properties throughout this time, including Fc receptors and staining for non-specific esterase. The cell lines phagocytosed IgG-coated particles, they were positive for the murine macrophage-specific marker F4/80 and they showed antigen-presentation function. Lysozyme, acid phosphatase, plasminogen activator, collagenase, prostaglandin E2 and 5'-nucleotidase activities have also been detected in these lines. In this paper the method of DNA transformation will be described as well as some of the assays used for the characterization of the three immortalized cell lines.
Analysis of the adenylate cyclase signalling system, and alterations induced by culture with insulin, in a novel SV40-DNA-immortalized hepatocyte cell line (P9 cells).
An immortalized cell line, called P9, was derived from hepatocytes by transfection with SV40 DNA. These cells expressed enzyme activities characteristic of hepatocytes, namely glucose-6-phosphatase, glycogen phosphorylase, bilirubin glucuronyltransferase and both glucagon- and prostaglandin E1 (PGE1)-stimulated adenylate cyclase activities, albeit at decreased levels compared with native hepatocytes. Levels of the G-protein subunits alpha-Gi-2, alpha-Gi-3, G beta and the 'long' form of alpha-G2 (45 kDa) were approximately 4-fold higher relative to native hepatocytes, whereas those of the 'short' form of alpha-G2 (42 kDa) were lower by approximately 40%. Associated with this were marked alterations in the guanine nucleotide regulation of adenylate cyclase. Receptor-mediated stimulation, achieved by either PGE1 or glucagon, was apparent in P9 cells, although the latter was only evident upon amplification with forskolin. Glucagon-stimulated cyclic AMP accumulation in P9 cells did not exhibit desensitization, as in hepatocytes, nor was the phosphorylation of alpha-Gi-2 evident. Culture of P9 cells with insulin led to a dose-dependent decrease (EC50 0.2 +/- 0.1 nM) in the ability of PGE1 to stimulate adenylate cyclase activity, with the maximum effect attained after approximately 6 h. A comparable attenuation of stimulation was seen for glucagon- and guanine-nucleotide-stimulated adenylate cyclase activities. In cells cultured with insulin, lower levels of GTP were required to stimulate adenylate cyclase, ADP-ribosylation of the 45 kDa form of alpha-Gs with cholera toxin was attenuated, and the expression of both alpha Gi-2 and alpha-Gi-3 was increased. It is suggested that the expression of alpha-Gi-2 and alpha-Gi-3 may be directly regulated by the action of insulin in hepatocytes and P9 cells.
Production of immortal human endothelial cell lines by strontium phosphate transfection and electroporation of SV40 sequences.
Eleven human endothelial cell lines have been produced by introducing sequences from the DNA tumor virus SV40 into human umbilical vein endothelial cells either by strontium phosphate coprecipitation or electroporation. The resultant lines were confirmed as being endothelial in origin by their production of endothelial-specific von Willebrand factor. The growth characteristics of the different lines in normal and reduced levels of serum was determined, as was their cellular response to endothelial cell growth supplement in combination with heparin, basic fibroblast growth factor, transforming growth factor-alpha, and epidermal growth factor.
Dual task performance in amnesic and normal people: does resource depletion cause amnesia?
Normal peoples' memory can be seriously disrupted if their cognitive resources are depleted by means of an experimental manipulation (such as distraction at encoding or at retrieval). By analogy, it has also been suggested that amnesia might result directly from pathological loss of cognitive capacity. This hypothesis was examined in 12 mixed amnesics and 12 normal people by means of a 'dual task' study. It was argued that if amnesics have reduced cognitive resources they should be disproportionately impaired in dual task performance relative to single task performance and in comparison to controls. This result was unambiguously demonstrated using a visual (letter detection) task combined with an auditory (semantic decision) task. However, correlations with measures of frontal function and with indicants of severity of amnesia proved insignificant and so the role of resource depletion in amnesia remains, as yet, unproven.
Magnetic resonance imaging of the iliofemoral arteries after balloon dilation angioplasty of aortic arch obstructions in children.
BACKGROUND: We wished to determine the nature and incidence of changes in the iliofemoral arteries after balloon dilation angioplasty (BDA) for aortic arch obstruction in children and to determine the reliability of gradient magnetic resonance imaging (MRI) in their detection. METHODS AND RESULTS: Sixty-three children, including 62 with and 1 without arch obstruction, underwent MRI of the iliofemoral vessels. Of these, 36 patients had undergone transfemoral BDA (7 after previous transfemoral diagnostic catheterization), 12 had undergone diagnostic transfemoral catheterization but not BDA, and 15 had no history of femoral arterial catheterization. The iliofemoral arteries were normal on MRI in all 15 children without catheterization. Among the 36 children who had undergone BDA, the ipsilateral iliofemoral artery was normal in 15, mildly narrowing in 7, and severely stenotic or occluded in 14 (39%), including 6 of 9 patients treated for acute femoral artery thrombosis and 8 with no history of femoral artery thrombosis. Two patients had documentation of progressive obstruction. Six patients had concordant conventional angiography. There was a significant correlation between the number of balloon catheters used for the angioplasty and severe occlusive changes. Nine of 19 patients who had undergone diagnostic transfemoral catheterization had severe obstructive changes on MRI; 8 of 9 weighed < 10 kg at catheterization. CONCLUSIONS: Obstructive lesions of the iliofemoral arteries are common after transfemoral BDA of arch obstructions (58%) and can be reliably evaluated with gradient MRI. Catheter size and manipulation are the main contributing factors.
Expression of liver functions in immortalised rat hepatocyte cell lines.
The differentiated hepatic function of two rat liver cell lines, P9 and SV40RH1, immortalised by transfection with SV40 DNA has been investigated in terms of the glutathione synthesis, and the activities of gamma-glutamyltransferase, glutathione-S-transferase and UDP-glucuronosyltransferase. SV40RH1 is a highly differentiated cell line at early passage, but the expression of some aspects of its differentiated phenotype is unstable and some functions are lost by passage 12-13. P9 is a less-well differentiated cell line, with relatively stable expression of functions between passages 4 and 13. In terms of differentiated function both cell lines represent a marked improvement over primary cultures of rat hepatocytes which de-differentiate rapidly within 24-48 h in culture. This retention of liver function in proliferating cell lines offers the opportunity to use such cells in in vitro toxicological studies.
A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression.
OBJECTIVE: To directly compare the efficacy of lithium carbonate and liothyronine sodium (triiodothyronine) in the augmentation of therapeutic response in antidepressant nonresponders. DESIGN: A randomized, double-blind, placebo-controlled study of 2 weeks' duration. SETTING: The Mood Disorders Program, Clarke Institute of Psychiatry and the University of Toronto, Ontario. PATIENTS: Fifty outpatients, males and females, with unipolar, nonpsychotic major depression who had failed to respond to treatment with desipramine hydrochloride or imipramine hydrochloride. RESULTS: Both liothyronine and lithium were more effective than placebo in reducing scores on the Hamilton Rating Scale for Depression. However, the antidepressant augmenting effect of these two compounds did not differ from each other. When response was defined as a 50% or more reduction in the Hamilton Rating Scale for Depression scores and a final score less than 10, we found that 10 of 17 subjects responded to liothyronine, nine of 17 responded to lithium and three of 16 responded to placebo. CONCLUSIONS: Our study suggests that both lithium and liothyronine may be considered as alternatives in augmenting antidepressant response in patients who do not respond to treatment with a tricyclic antidepressant.
Safety, success, and restenosis after elective coronary implantation of the Palmaz-Schatz stent in 100 patients at a single center.
We report the immediate safety, efficacy, and 6-month angiographic follow-up after elective implantation of the Palmaz-Schatz stent (Johnson & Johnson Interventional Systems, Warren, N.J.) in the first 100 consecutive patients at a single center. Patients with suitable cardiac anatomy and no contraindications to anticoagulation were prospectively entered into the study. One hundred two stents were successfully implanted in 99 patients. The mean diameter stenosis was 70% +/- 11% before implantation and was reduced to 20% +/- 11% after stent implantation. There were no deaths, Q-wave myocardial infarcts, urgent bypass operations, or strokes during the procedure or follow-up period. Stent thrombosis occurred in two patients; in both vessel patency was successfully accomplished by balloon angioplasty. There were three gastrointestinal hemorrhages, two of which required transfusion. Angiographic follow-up was performed in 98% of patients at 6.3 +/- 2.6 months after the procedure. Restenosis (> or = 50% stenosis within or immediately adjacent to the stent) occurred in 32%. Stent restenosis was associated with male sex (36% vs 7% for female subjects; p = 0.03) and stent implantation in a restenosis lesion (47% vs 25% for de novo lesions; p = 0.03); it was inversely associated with current cigarette smoking (0% vs 36% for nonsmokers; p = 0.02). In conclusion, the Palmaz-Schatz stent can be electively implanted with high success and low complication rates. The restenosis rate appears to be similar to that of balloon angioplasty.
Anxiety disorders and anxiety symptoms in a clinic sample of seasonal and non-seasonal depressives.
Thirty-eight patients with seasonal affective disorder (SAD) were compared with 33 non-seasonal recurrent major depressives (non-SAD) who presented during the winter months for differences in the prevalence of concurrent anxiety disorders and the impact of anxiety on treatment response. SAD patients received light therapy, whereas non-SAD patients received antidepressant medications. There was no differences in the prevalence of any anxiety disorder, or on scores of anxiety on the Hamilton Rating Scale for Depression between the SAD and non-SAD groups. The presence of any anxiety disorder was associated with a better response rate in SAD patients, and an inferior response rate in non-SAD patients. The findings refute previous suggestions that anxiety is more common in SAD than in non-SAD, but suggest that the presence of anxiety may be associated with differential treatment response rates.
A comparison of the cardiac safety and therapeutic efficacy of trimipramine versus doxepin in geriatric depressed patients.
OBJECTIVE: To compare the cardiac safety and therapeutic efficacy of trimipramine and doxepin. DESIGN: A 1-week single-blind placebo period followed by a 5-week randomized double-blind parallel group clinical trial. SETTING: Psychiatric out-patient clinic of a general hospital. PATIENTS: 37 young-elderly patients with a diagnosis of Major Depressive Episode (DSM-III criteria). INTERVENTIONS: Placebo for 1 week, 2 weeks of titration with either drug in the dosage range of 75 mg/day up to a maximum of 200 mg/day. MEASUREMENTS: We measured the psychiatric effects with the Hamilton Rating Scale for Depression, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression Scale. Cardiovascular effects were assessed on 12-lead standard electrocardiograms plus 1-minute rhythm and high speed recordings; orthostatic (lying/standing) blood pressures were also taken. Physical exams, lab tests, cognitive functions (Buschke Selective Reminding Test, Hierarchic Dementia Scale, Word Fluency) and adverse reactions were also noted. RESULTS: Both drugs were equally effective in relieving symptoms of depression and anxiety. The cardiovascular effects of both drugs were minimal. Trimipramine did lower blood pressure but this was without clinical significance. Three trimipramine patients and five doxepin patients developed occasional premature ventricular or atrial contractions. Of these, two trimipramine patients and one doxepin patient were among those with abnormal ECG's at entry. The doxepin patient was withdrawn from the study after 21 days of treatment when the PVC's became increasingly frequent. CONCLUSIONS: Trimipramine and doxepin are equally safe and effective antidepressants in the young-elderly.
Predictors of response to lithium and triiodothyronine augmentation of antidepressants in tricyclic non-responders.
Although both lithium and triiodothyronine (T3) augmentation strategies may be rapid, safe, and effective ways of treating patients who fail to respond to tricyclics, little is known about the clinical or biochemical correlates of response. We examined clinical and endocrine variables which distinguished T3 and lithium responders from each other and from non-responders in a post-hoc analysis of two studies involving 51 subjects who had received these augmentation strategies under double-blind conditions. Lithium non-responders were more severely depressed and had more insomnia and weight loss than responders. T3 responders could be distinguished from lithium responders by greater weight loss. There were no reliable clinical differences between T3 responders and non-responders. Thyroid function tests did not differ between any of the treatment or response groups. Our findings suggest that clinical but not endocrine variables may distinguish responders to these two augmentation strategies.
Immortalization of murine primary spleen cells by v-myc, v-ras, and v-raf.
Growth factor-independent cell lines, including four lines characterized as macrophages, were isolated by infection of BALB/c mouse primary spleen cells with combinations of three retroviruses encoding v-myc, v-ras, and v-myc/v-raf. Proliferating cell lines were isolated only rarely, and after long crisis periods, following the introduction of myc and raf by infection with J2 virus, or of myc and ras by coinfection with myc309 and raszip6 viruses. However, sequential infections with all three viruses--myc plus ras cells reinfected with J2, or J2 followed by myc plus ras coinfection--resulted in rapid outgrowth of cell lines which grew at high growth rates to high densities. When cells were treated with anti-IgG F(ab')2/IL-4/IL-5 to specifically stimulate B cells, cell lines were isolated readily by infection with myc plus ras alone, J2 alone, or all three viruses. These cell lines arose after shorter crisis times and all grew at high growth rates and to high densities. Analysis of cell surface markers and immunoglobulin gene arrangement revealed no lymphoid characteristics in any of the lines. Four cell lines express all three macrophage markers analyzed (F4/80, Mac1, FcR), and many others are Mac1+ and/or FcR+. Out of 20 immortalized cell lines tested, 13 show clonal growth in soft agar, and 3/6 of these produced tumors in BALB/c mice, indicating that fully transformed cells may be isolated by these procedures. In at least one of the cell lines, integration of all three infecting viruses has occurred.
Amnesics have a disproportionately severe memory deficit for interactive context.
Two experiments were used to compare the recognition memory of amnesic and normal subjects for intentionally encoded words (targets) and for incidentally encoded words that were meaningfully related to the targets and presented at the same time (interactive context). In both experiments the target recognition of the two groups was matched at a high level by presenting the amnesics with much shorter lists of words to remember. Experiment 1 compared 20 amnesics and their matched controls and showed that whereas the amnesics' recognition of the target words did not benefit significantly when they were presented together with their interactive context words (relative to their recognition when the target words were presented alone), that of the controls did. Experiment 2 compared 14 amnesics and their matched controls and showed that when patients and their controls were matched on their target word recognition in isolation, then the patients still showed worse recognition for the interactive context words. These effects were not found only in Korsakoff patients, and their size did not correlate with behavioural measures of frontal-lobe damage. It is concluded that amnesics may be more impaired at recognizing incidentally encoded interactive context than they are at recognizing target material, and this deficit may be an essential feature of the syndrome.