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Biomedical subjects

R McLeod

Publications and source records attributed to R McLeod.

At least 19 recordsLinked to original sources
PubMed2006

Enzymes of type II fatty acid synthesis and apicoplast differentiation and division in Eimeria tenella.

Apicomplexan parasites, Eimeria tenella, Plasmodium spp. and Toxoplasma gondii, possess a homologous plastid-like organelle termed the apicoplast, derived from the endosymbiotic enslavement of a photosynthetic alga. However, currently no eimerian nuclear encoded apicoplast targeted proteins have been identified, unlike in Plasmodium spp. and T. gondii. In this study, we demonstrate that nuclear encoded enoyl reductase of E. tenella (EtENR) has a predicted N-terminal bipartite transit sequence, typical of apicoplast-targeted proteins. Using a combination of immunocytochemistry and EM we demonstrate that this fatty acid biosynthesis protein is located in the apicoplast of E. tenella. Using the EtENR as a tool to mark apicoplast development during the Eimeria lifecycle, we demonstrate that nuclear and apicoplast division appear to be independent events, both organelles dividing prior to daughter cell formation, with each daughter cell possessing one to four apicoplasts. We believe this is the first report of multiple apicoplasts present in the infectious stage of an apicomplexan parasite. Furthermore, the microgametes lacked an identifiable apicoplast consistent with maternal inheritance via the macrogamete. It was found that the size of the organelle and the abundance of EtENR varied with developmental stage of the E. tenella lifecycle. The high levels of EtENR protein observed during asexual development and macrogametogony is potentially associated with the increased synthesis of fatty acids required for the rapid formation of numerous merozoites and for the extracellular development and survival of the oocyst. Taken together the data demonstrate that the E. tenella apicoplast participates in type II fatty acid biosynthesis with increased expression of ENR during parasite growth. Apicoplast division results in the simultaneous formation of multiple fragments. The division mechanism is unknown, but is independent of nuclear division and occurs prior to daughter formation.

Amino Acid Sequence↗
PubMed2005

Light-weight lead aprons--light on weight, protection or labelling accuracy?

X-ray transmission tests were performed on a Green-Lite (Infab Corporation) apron/vest combination, and compared to a number of other apron/vest combinations routinely used at Christchurch Hospital as well as a sheet of 0.5 mm lead. The materials were X-rayed using the primary beam of a Philips Optimus 50 X-ray machine over an energy range of 50-125 kVp. The entrance and exit doses were recorded and percentage transmission calculated for each kVp. The Green-Lite apron/vest (labelled as 0.5 mm lead at 85 kVp) relies on the overlap at the front to provide the nominal 0.5 mm protection for both the vest and the apron. It performed significantly worse than 0.5 mm of lead and other 0.5 mm lead equivalent apron/vest combinations and provided between 0.3 and 0.39 mm lead equivalent protection depending on the energy used. Vests from other manufacturers all achieved 0.5 mm lead equivalence for a single layer of vest material over the range of energies tested and so were comparable to 1.0 mm lead when doubled. Some aprons relied on a double layer of material to achieve the 0.5 mm lead equivalence (which was not always made clear on the label), while others stated their lead equivalence for a single layer. This resulted in some confusion among wearers of the aprons as to which apron was better.

Equipment Failure Analysis↗
PubMed2005

Toxoplasma gondii dense granule protein 3 (GRA3) is a type I transmembrane protein that possesses a cytoplasmic dilysine (KKXX) endoplasmic reticulum (ER) retrieval motif.

Studies using antibodies to immunolocalize the Toxoplasma gondii dense granule protein GRA3, have shown that this protein associates strongly with the parasitophorous vacuole membrane (PVM). However, as there was no predicted membrane-spanning domain this highlighted an unanswered paradox. We demonstrate that the previously published sequence for GRA3 is actually an artificial chimera of 2 proteins. One protein, of molecular weight 65 kDa, shares the C-terminus with published GRA3 and possesses no significant sequence similarity with any protein thus far deposited in Genbank. The second, with a predicted molecular weight of 24 kDa shares the N-terminal region, is recognized by the monoclonal antibody 2H11 known to react with the dense granules of T. gondii and is therefore the authentic GRA3. The corrected GRA3 has an N-terminal secretory signal sequence and a transmembrane domain consistent with its insertion into the PVM. Antibodies to recombinant GRA3 recognize a protein of 24 kDa in T. gondii excretory-secretory antigen preparations. The signal peptide is necessary and sufficient to target GFP to the dense granules and parasitophorous vacuole. A homologue was identified in Neospora caninum. Finally, GRA3 possesses a dilysine 'KKXX' endoplasmic reticulum (ER) retrieval motif that rationalizes its association with PVM and possibly the host cell ER.

Amino Acid Motifs↗
PubMed2005

Management of the patient and family with neurofibromatosis 2: a consensus conference statement.

A consensus conference on neurofibromatosis 2 (NF2) was held in 2002 at the request of the United Kingdom (UK) Neurofibromatosis Association, with particular emphasis on vestibular schwannoma (VS) surgery. NF2 patients should be managed at specialty treatment centres, whose staff has extensive experience with the disease. All NF2 patients and their families should have access to genetic testing because presymptomatic diagnosis improves the clinical management of the disease. Some clinical manifestations of NF2, such as ocular abnormalities, can be detected in infancy; therefore, clinical screening for at-risk members of NF2 families can start at birth, with the first magnetic resonance (MRI) scan at 10-12 years of age. Minimal interference, maintenance of quality of life, and conservation of function or auditory rehabilitation are the cornerstones of NF2 management, and the decision points to achieve these goals for patients with different clinical presentations are discussed.

Adult↗
PubMed2005

Electrical impedance scanning for melanoma diagnosis: a validation study.

BACKGROUND: A multicenter study was conducted to test the ability of electrical impedance scanning to differentiate between benign and malignant skin lesions. The performance of a dual electrical impedance scanning/image analysis device was also assessed. METHODS: Electrical impedance scanning measurements of 449 preoperative lesions found on 382 patients and including 53 melanomas from the trunk and extremities were performed. Results were correlated with histopathologic findings. In addition, ABCD parameters for the lesions were automatically calculated by the system. RESULTS: Electrical impedance scanning detected melanomas of the trunk and extremities with 91 percent sensitivity and 64 percent specificity. Moreover, sensitivity of electrical impedance scanning was increased to 100 percent for in situ and thin melanomas of smaller size (n = 27). Visual examination identified as malignant only 67 percent of these early tumors (p = 0.002). Clinical examination detected 96 percent of the larger or thicker melanomas (n = 26), whereas electrical impedance scanning detected only 81 percent of them. Combined electrical impedance scanning and image analysis detected 100 percent of the melanomas, independent of their thickness, and with no significant decrease of specificity. Because of electrical differences between the head/neck and the rest of the body, the assessed electrical impedance scanning parameters were not adequate for the diagnosis of melanomas from the head and neck. CONCLUSIONS: A validation study proved the value of electrical impedance scanning as a noninvasive technique for detection of melanoma lesions of the trunk and extremities, specifically, of in situ and thin type. In addition, image analysis was shown to be a valuable, complementary procedure. New parameters should be designed to optimize the performance of electrical impedance scanning for melanomas of the head and neck.

Adult↗
PubMed2004

A complete shikimate pathway in Toxoplasma gondii: an ancient eukaryotic innovation.

The shikimate pathway is essential for survival of the apicomplexan parasites Plasmodium falciparum, Toxoplasma gondii and Cryptosporidium parvum. As it is absent in mammals it is a promising therapeutic target. Herein, we describe the genes encoding the shikimate pathway enzymes in T. gondii. The molecular arrangement and phylogeny of the proteins suggests homology with the eukaryotic fungal enzymes, including a pentafunctional AROM. Current rooting of the eukaryotic evolutionary tree infers that the fungi and apicomplexan lineages diverged deeply, suggesting that the arom is an ancient supergene present in early eukaryotes and subsequently lost or replaced in a number of lineages.

Alcohol Oxidoreductases↗
PubMed2003

Delivery of antimicrobials into parasites.

To eliminate apicomplexan parasites, inhibitory compounds must cross host cell, parasitophorous vacuole, and parasite membranes and cyst walls, making delivery challenging. Here, we show that short oligomers of arginine enter Toxoplasma gondii tachyzoites and encysted bradyzoites. Triclosan, which inhibits enoyl-ACP reductase (ENR), conjugated to arginine oligomers enters extracellular tachyzoites, host cells, tachyzoites inside parasitophorous vacuoles within host cells, extracellular bradyzoites, and bradyzoites within cysts. We identify, clone, and sequence T. gondii enr and produce and characterize enzymatically active, recombinant ENR. This enzyme has the requisite amino acids to bind triclosan. Triclosan released after conjugation to octaarginine via a readily hydrolyzable ester linkage inhibits ENR activity, tachyzoites in vitro, and tachyzoites in mice. Delivery of an inhibitor to a microorganism via conjugation to octaarginine provides an approach to transporting antimicrobials and other small molecules to sequestered parasites, a model system to characterize transport across multiple membrane barriers and structures, a widely applicable paradigm for treatment of active and encysted apicomplexan and other infections, and a generic proof of principle for a mechanism of medicine delivery.

Amino Acid Sequence↗
PubMed2003

Fatty acid and sterol metabolism: potential antimicrobial targets in apicomplexan and trypanosomatid parasitic protozoa.

Current treatments for diseases caused by apicomplexan and trypanosomatid parasites are inadequate due to toxicity, the development of drug resistance and an inability to eliminate all life cycle stages of these parasites from the host. New therapeutics agents are urgently required. It has recently been demonstrated that type II fatty acid biosynthesis occurs in the plastid of Plasmodium falciparum and Toxoplasma gondii and inhibitors of this pathway such as triclosan and thiolactomycin restrict their growth. Furthermore, Trypanosoma brucei has recently been demonstrated to use type II fatty acid biosynthesis for myristate synthesis and to be susceptible to thiolactomycin. As this pathway is absent from mammals, it may provide an excellent target for novel antimicrobial agents to combat these diverse parasites. Leishmania and Trypanosoma parasites produce ergosterol-related sterols by a biosynthetic pathway similar to that operating in pathogenic fungi and their growth is susceptible to sterol biosynthesis inhibitors. Thus, inhibition of squalene 2,3-epoxidase by terbinafine, 14alpha-methylsterol 14-demethylase by azole and triazole compounds and delta(24)-sterol methyl transferase by azasterols all cause a depletion of normal sterols and an accumulation of abnormal amounts of sterol precursors with cytostatic or cytoxic consequences. However, Leishmania parasites can survive with greatly altered sterol profiles induced by continuous treatment with low concentrations of some inhibitors and they also have some ability to utilise and metabolise host sterol. These properties may permit the parasites to evade treatment with sterol biosynthesis inhibitors in some clinical situations and need to be taken into account in the design of future drugs.

Animals↗
PubMed2002

Ultra-relativistic electrons in Jupiter's radiation belts.

Ground-based observations have shown that Jupiter is a two-component source of microwave radio emission: thermal atmospheric emission and synchrotron emission from energetic electrons spiralling in Jupiter's magnetic field. Later in situ measurements confirmed the existence of Jupiter's high-energy electron-radiation belts, with evidence for electrons at energies up to 20[?]MeV. Although most radiation belt models predict electrons at higher energies, adiabatic diffusion theory can account only for energies up to around 20[?]MeV. Unambiguous evidence for more energetic electrons is lacking. Here we report observations of 13.8[?]GHz synchrotron emission that confirm the presence of electrons with energies up to 50[?]MeV; the data were collected during the Cassini fly-by of Jupiter. These energetic electrons may be repeatedly accelerated through an interaction with plasma waves, which can transfer energy into the electrons. Preliminary comparison of our data with model results suggests that electrons with energies of less than 20[?]MeV are more numerous than previously believed.

Journal Article↗
PubMed2001

Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I.

Fab I, enoyl acyl carrier protein reductase (ENR), is an enzyme used in fatty acid synthesis. It is a single chain polypeptide in plants, bacteria, and mycobacteria, but is part of a complex polypeptide in animals and fungi. Certain other enzymes in fatty acid synthesis in apicomplexan parasites appear to have multiple forms, homologous to either a plastid, plant-like single chain enzyme or more like the animal complex polypeptide chain. We identified a plant-like Fab I in Plasmodium falciparum and modelled the structure on the Brassica napus and Escherichia coli structures, alone and complexed to triclosan (5-chloro-2-[2,4 dichlorophenoxy] phenol]), which confirmed all the requisite features of an ENR and its interactions with triclosan. Like the remarkable effect of triclosan on a wide variety of bacteria, this compound markedly inhibits growth and survival of the apicomplexan parasites P. falciparum and Toxoplasma gondii at low (i.e. IC50 congruent with150-2000 and 62 ng/ml, respectively) concentrations. Discovery and characterisation of an apicomplexan Fab I and discovery of triclosan as lead compound provide means to rationally design novel inhibitory compounds.

Amino Acid Sequence↗
PubMed2001

Construction and validation of a polycompetitor construct (SWITCH) for use in competitive RT-PCR to assess tachyzoite-bradyzoite interconversion in Toxoplasma gondii.

The obligate intracellular protozoan parasite, Toxoplasma gondii exists as 2 life-cycle forms in intermediate hosts. The rapidly dividing tachyzoites responsible for acute disease, present in the first 14 days of infection, give rise to slowly dividing bradyzoites that reside in tissue cysts. Reactivation of disease is associated with conversion of bradyzoites to tachyzoites. A sensitive method for detection and assessment of the number of each life-cycle stage would be useful for following these events. Herein we describe the construction and validation of a plasmid (pSWITCH) containing a polycompetitor construct (SWITCH) for use in competitive reverse transcriptase-PCR (cRT-PCR). pSWITCH contains competitors for SAG2A and LDH2 genes, which are exclusively expressed by tachyzoite and bradyzoite stages respectively, and for beta-tubulin, a gene expressed by both stages. Using cRT-PCR, samples can first be accurately normalized for expression of the housekeeping gene, beta-tubulin and then the relative levels of SAG2A and LDH2 expression compared to follow stage conversion. The abundance of transcripts for other genes of interest can then be followed during this process as demonstrated here for the SAG2-related family of genes. This technique offers a powerful tool for studying the processes involved in tachyzoite and bradyzoite interconversion.

Animals↗
PubMed2001

Concerns of patients with inflammatory bowel disease: results from a clinical population.

OBJECTIVE: The impact of chronic illness is influenced not just by physical symptoms but also by psychosocial factors. The aim of this study was to determine the concerns of inflammatory bowel disease (IBD) patients in a clinical sample, if concerns differ between patients from varied clinical and demographic variables, and if concerns influence well-being beyond the influence of physical symptoms. METHODS: Subjects (n = 259) completed a validated measure of concerns specific to IBD and provided demographic and disease-related information. RESULTS: The most intense concerns involved both physical (e.g., energy level) and psychosocial issues (e.g., achieving full potential). There were numerous differences in disease concerns based on ability to work but none based on disease duration. Factor analysis yielded three indices: body image and interpersonal concerns, general physical impact, and disease stigma. Age and education only affected certain concern indices in subgroups of patients. Greater concerns negatively influenced well-being beyond the influence of physical symptoms. CONCLUSION: Psychosocial factors, in addition to physical symptoms, play an important role on the impact of illness in patients with IBD.

Adult↗
PubMed2001

Histopathological features of ocular toxoplasmosis in the fetus and infant.

BACKGROUND: Ocular disease is a frequent manifestation of congenital Toxoplasma gondii infection. There are only limited data available in the literature concerning early stages of this disease in fetuses and infants. The purpose of our study was to characterize histopathological features in the eyes of 10 fetuses and 2 infants with congenital toxoplasmosis. METHODS: Fifteen eyes from 10 fetuses, 3 eyes from 2 premature infants, and both eyes from a 2-year-old child with congenital toxoplasmosis were examined by light microscopy. Immunohistochemical analysis to identify inflammatory cells and T gondii antigens was performed. The findings in infected eyes were compared with those of age-matched control eyes. RESULTS: Retinitis (10/18 eyes), retinal necrosis (4/18 eyes), disruption of the retinal pigment epithelium (12/18 eyes), and choroidal inflammation and congestion (15/18 eyes) were characteristic findings. Optic neuritis was present in 5 of 8 fetal eyes with associated optic nerve available for evaluation. An eye obtained from a 32-week-old fetus showed retinal rosettes at the edge of a scar. T cells predominated in retinal lesions and choroid. Parasites were identified by immunohistochemical analysis in 10 of 18 eyes. CONCLUSIONS: Ocular toxoplasmosis causes irreversible damage to the retina in utero. The fetus and infant mount inflammatory responses that may contribute to ocular damage. These findings have important implications for serological screening programs and in utero therapy.

Antigens, CD↗
PubMed2000

Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III.

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.

Adolescent↗
PubMed2000

Chemoprevention of aflatoxin B1 hepatocarcinogenesis by coumarin, a natural benzopyrone that is a potent inducer of aflatoxin B1-aldehyde reductase, the glutathione S-transferase A5 and P1 subunits, and NAD(P)H:quinone oxidoreductase in rat liver.

Structurally diverse compounds can confer resistance to aflatoxin B1 (AFB1) hepatocarcinogenesis in the rat. Treatment with either phytochemicals [benzyl isothiocyanate, coumarin (CMRN), or indole-3-carbinol] or synthetic antioxidants and other drugs (butylated hydroxyanisole, diethyl maleate, ethoxyquin, beta-naphthoflavone, oltipraz, phenobarbital, or trans-stilbene oxide) has been found to increase hepatic aldo-keto reductase activity toward AFB1-dialdehyde and glutathione S-transferase (GST) activity toward AFB1-8,9-epoxide in both male and female rats. Under the conditions used, the natural benzopyrone CMRN was a major inducer of the AFB1 aldehyde reductase (AFAR) and the aflatoxin-conjugating class-alpha GST A5 subunit in rat liver, causing elevations of between 25- and 35-fold in hepatic levels of these proteins. Induction was not limited to AFAR and GSTA5: treatment with CMRN caused similar increases in the amount of the class-pi GST P1 subunit and NAD(P)H: quinone oxidoreductase in rat liver. Immunohistochemistry demonstrated that the overexpression of AFAR, GSTA5, GSTP1, and NAD(P)H:quinone oxidoreductase affected by CMRN is restricted to the centrilobular (periacinar) zone of the lobule, sometimes extending almost as far as the portal tract. This pattern of induction was also observed with ethoxyquin, oltipraz, and trans-stilbene oxide. By contrast, induction of these proteins by beta-naphthoflavone and diethyl maleate was predominantly periportal. Northern blotting showed that induction of these phase II drug-metabolizing enzymes by CMRN was accompanied by similar increases in the levels of their mRNAs. To assess the biological significance of enzyme induction by dietary CMRN, two intervention studies were performed in which the ability of the benzopyrone to inhibit either AFB1-initiated preneoplastic nodules (at 13 weeks) or AFB1-initiated liver tumors (at 50 weeks) was investigated. Animals pretreated with CMRN for 2 weeks prior to administration of AFB1, and with continued treatment during exposure to the carcinogen for a further 11 weeks, were protected completely from development of hepatic preneoplastic lesions by 13 weeks. In the longer-term dietary intervention, treatment with CMRN before and during exposure to AFB1 for a total of 24 weeks was found to significantly inhibit the number and size of tumors that subsequently developed by 50 weeks. These data suggest that consumption of a CMRN-containing diet provides substantial protection against the initiation of AFB1 hepatocarcinogenesis in the rat.

Aflatoxin B1↗
PubMed2000

Pharmacotherapy for inducing and maintaining remission in pouchitis.

OBJECTIVES: To determine the effectiveness of medical therapy (including metronidazole, bismuth carbomer enemas, oral probiotic bacteria, butyrate suppositories, and glutamine suppositories) for inducing a response or maintaining remission in pouchitis. SEARCH STRATEGY: Studies were selected using the MEDLINE data base (1966 - December 1997), abstracts from major gastrointestinal meetings and references from published articles and reviews. The Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Register were also searched. SELECTION CRITERIA: Four randomized controlled trials of medical therapy in adult patients with pouchitis were identified: two placebo controlled trials in active chronic pouchitis; one maintenance of remission trial comparing two active agents in chronic pouchitis; and one placebo-controlled maintenance of remission trial for chronic pouchitis. A single patient "n-of-1" trial for active chronic pouchitis was excluded. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent observers based on the intention to treat principle. Each study was given a quality score based on predetermined criteria. Extracted data were converted to 2X2 tables (response versus no response and medical therapy versus placebo or medical therapy versus medical therapy) and then synthesized in to a summary statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel (the "odds ratio" in MetaView). MAIN RESULTS: The odds ratios of inducing a response using oral metronidazole or bismuth carbomer foam enemas compared with placebo in active chronic pouchitis were 26.67 (95% CI 2.31-308.01) and 1.00 (95% CI 0.29-3.48), respectively. The numbers needed to treat with these therapies to prevent an additional relapse was 2 for oral metronidazole, and undefined for bismuth carbomer foam enemas (due to equal efficacy between the enema and placebo). The odds ratio of maintaining remission in chronic pouchitis for oral probiotic bacteria (VSL-3) compared with placebo was 205.00 (95% CI 9.89-4247.71), while the number needed to treat to prevent one additional relapse was 2. After discontinuation of suppressive medical therapy for chronic pouchitis, there was no difference in the odds ratio of maintaining symptomatic remission with glutamine suppositories compared to butyrate suppositories, 3. 00 (95% CI 0.46-19.59). The numbers needed to treat with glutamine suppositories to prevent an additional relapse was 4. REVIEWER'S CONCLUSIONS: The results presented in this review must be interpreted with extreme caution given the small numbers of trials and patients evaluated for any one comparison. Metronidazole appears to be an effective therapy for active chronic pouchitis. Bismuth carbomer foam enemas may not be an effective therapy for chronic active pouchitis. Oral probiotic therapy with VSL-3 appears to be an effective therapy for maintaining remission in patients with chronic pouchitis in remission. There is no evidence of a difference in the maintenance of symptomatic remission in patients with chronic pouchitis treated with glutamine versus butyrate suppositories, and it is unknown whether glutamine and butyrate are equally effective or ineffective. Additional randomized, double-blind, placebo-controlled, dose-ranging clinical trials are needed to determine the efficacy of empiric medical therapies currently being used in patients with pouchitis.

Adult↗
PubMed2000

Self-reported effects of computer workshops on physicians' computer use.

BACKGROUND: The need for physicians to be proficient in the use of computers is undeniable. As computers have become easier to use and more widespread, their use in medicine is expanding. Several organizations have produced continuing medical education programs to teach physicians about the use of computers in medicine but little has been reported on the effects of such programs. METHOD: We present the self-reported effects of a series of workshops that taught physicians about basic computer skills: information retrieval, the Internet, CD-ROMs, electronic mail, and computer-aided learning. RESULTS: A questionnaire mailed to 65 workshop participants yielded a response rate of 46% (n = 30). Of the 30 respondents, 27% (n = 8) had bought new hardware or software because of attending the workshops, with the most common purchase being a new computer. Fifty-seven percent (n = 17) had increased their use of computers, with the most common applications being use of the Internet for information retrieval and electronic mail.

Computer User Training↗