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Biomedical subjects

R E Clark

Publications and source records attributed to R E Clark.

At least 55 records · Page 3Linked to original sources
PubMed1999

Research on the individual placement and support model of supported employment.

This paper reviews research on the Individual Placement and Support (IPS) model of supported employment for people with severe mental illness. Current evidence indicates that IPS supported employment is a more effective approach for helping people with psychiatric disabilities to find and maintain competitive employment than rehabilitative day programs or than traditional, stepwise approaches to vocational rehabilitation. There is no evidence that the rapid-job-search, high-expectations approach of IPS produces untoward side effects. IPS positively affects satisfaction with finances and vocational services, but probably has minimal impact on clinical adjustment. The cost of IPS is similar to the costs of other vocational services, and cost reductions may occur when IPS displaces traditional day treatment programs. Future research should be directed at efforts to enhance job tenure and long-term vocational careers.

Cost-Benefit Analysis↗
PubMed1999

Clinical use of streptolysin-O to facilitate antisense oligodeoxyribonucleotide delivery for purging autografts in chronic myeloid leukaemia.

Antisense oligodeoxyribonucleotides (ODN) targeted against the breakpoint in BCR-ABL mRNA will specifically decrease BCR-ABL mRNA, provided cells are first permeabilised with streptolysin-O (SL-O). We used 18-mer chimeric methylphosphonodiester: phosphodiester linked (4-9-4) ODN complementary to 9 bases either side of the BCR-ABL junction to purge harvests ex vivo in three CML patients who remained completely Ph positive after multiple chemotherapy courses. After CD34+ cell selection and SL-O permeabilisation, harvests were purged with 20 microM ODN. After purging, all individual CFU-GM colonies grown from the two b3a2 breakpoint cases remained positive for BCR-ABL mRNA. In contrast, all 24 colonies grown from the b2a2 breakpoint case were BCR-ABL mRNA negative. Patients were conditioned with busulphan 16 mg/kg. The initial post-transplant course was uneventful, although the time to return to 0.5 x 10(9)/l neutrophils was slow at 25-51 days. Both chronic phase patients remain in haematological remission at +724 and +610 days, although each has cytogenetic evidence of relapse. The b2a2 accelerated phase patient died of myeloid blast transformation at day +91. The present SL-O-facilitated ODN purging strategy appears to be without significant toxicity, and offers considerable improvements in ODN delivery to the cytosol.

Antigens, CD34↗
PubMed1999

Chemotherapy-induced acral erythema (CIAE) with bullous reaction.

Chemotherapy-induced acral erythema (CIAE) is a cutaneous response to a number of different chemotherapeutic agents. It causes a symmetrical, painful erythema of both the palms and soles which is self-limiting. CIAE with bullous reaction has been reported in relation to methotrexate, but it has been more commonly associated with cytosine arabinoside. We describe a case of CIAE with bullous reaction in a patient treated for Hodgkin's disease with a number of chemotherapeutic agents. We discuss the differential diagnosis of this condition which includes eccrine squamous syringometaplasia and acute graft vs. host disease

Adult↗
PubMed1999

Identification of a good c-myc antisense oligodeoxynucleotide target site and the inactivity at this site of novel NCH triplet--targeting ribozymes.

A region of c-myc mRNA was identified which permitted very efficient antisense effects to be achieved in living cells using chimeric methylphosphonate--phosphodiester antisense effectors. Novel inosine--containing ribozymes (which cleave after NCH triplets) were directed to an ACA triplet within this region and delivered into living cells. No ribozyme intracellular activity could be identified. Very low ribozyme function was also observed in in vitro assays using a 1700nt substrate RNA.

Bacterial Proteins↗
PubMed1999

The effect of vertical dimension and mandibular position on isometric strength of the cervical flexors.

This study compared the peak isometric strength of the cervical flexors in deep bite temporomandibular dysfunction (TMD) patients while biting in four bite positions: habitual occlusion, edge-to-edge, lateral shift and retruded. These values were then compared to those of the same subjects' bite positions elevated to a functional criterion (maximum isometric strength of the deltoid muscles). The mean height increase was 2.4 mm with a range of 1.5-3.8 mm. Fifteen of eighteen deep bite subjects met an inclusionary criterion, at least 13.3 Newtons (N) stronger cervical muscle strength with mandible relaxed open than habitual bite. Peak strength biting edge-to-edge was significantly greater than biting in habitual occlusion. Strength was found to increase significantly when biting in each of four mandibular positions when the bite was elevated to the functional criterion. The greatest strength was obtained from elevated habitual and edge-to-edge positions. The findings are of clinical significance, suggesting that cervical muscle isometric strength is affected by bite position and vertical dimension of occlusion. The results suggest that when biting, individuals with deep bite may be functioning at about 60% of their potential cervical flexor, isometric strength. The interaction between occlusal position, vertical dimension and cervical muscle function suggests a craniomandibular-cervical masticatory system.

Adult↗
PubMed1999

Antisense morpholino oligonucleotide analog induces missplicing of C-myc mRNA.

A 28-mer morpholino oligonucleotide analog was designed to hybridize to 8 bases of intron 1 and extend 2 bases beyond the translation initiation codon in exon 2 of the unspliced c-myc RNA transcript. Delivery of this compound into human chronic myeloid leukemia KYO1 cells, by streptolysin O permeabilization, resulted in almost total ablation of the 65 kDa c-MYC protein expression for at least 24 hours after treatment. An unexpected band with SDS-PAGE electrophoretic mobility indicating a protein of about 47 kDa was apparent on the 24-hour western blots that were developed using antibodies that recognize MYC protein C terminal epitopes. No inhibition of the approximately 2400 nt c-myc mRNA expression was observed by northern hybridization, a result of the inability of morpholino analogs to direct the activity of ribonuclease H. In fact, high molecular weight c-myc RNA species were found to have accumulated in antisense-treated KYO1 cells. Control sense and scrambled antisense morpholino analogs did not inhibit MYC protein expression or induce the appearance of the anomalous RNA and protein bands. Molecular analyses by RT-PCR and sequencing revealed that the morpholino antisense effector had (1) inhibited splicing of the c-myc pre-mRNA, (2) induced missplicing of the pre-mRNA, and (3) inhibited translation of normal spliced c-myc mRNA. Identical results were obtained with acute promyelocytic leukemia, acute lymphoblastic leukemia, and histiocytic lymphoma cell lines.

Base Sequence↗
PubMed1999

Legal system involvement and costs for persons in treatment for severe mental illness and substance use disorders.

OBJECTIVE: Persons with co-occurring severe mental illness and substance use disorders were followed for three years to better understand how they are involved with the legal system and to identify factors associated with different kinds of involvement. METHODS: Data came from a three-year study of 203 persons enrolled in specialized treatment for dual disorders. Cost and utilization data were collected from multiple data sources, including police, sheriffs and deputies, officers of the court, public defenders, prosecutors, private attorneys, local and county jails, state prisons, and paid legal guardians. RESULTS: Over three years 169 participants (83 percent) had contact with the legal system, and 90 (44 percent) were arrested at least once. Participants were four times more likely to have encounters with the legal system that did not result in arrest than they were to be arrested. Costs associated with nonarrest encounters were significantly less than costs associated with arrests. Mean costs per person associated with an arrest were $2,295, and mean costs associated with a nonarrest encounter were $385. Combined three-year costs averaged $2,680 per person. Arrests and incarcerations declined over time. Continued substance use and unstable housing were associated with a greater likelihood of arrest. Poor treatment engagement was associated with multiple arrests. Men were more likely to be arrested, and women were more likely to be the victims of crime. CONCLUSIONS: Effective treatment of substance use among persons with mental illness appears to reduce arrests and incarcerations but not the frequency of nonarrest encounters. Stable housing may also reduce the likelihood and number of arrests.

Adult↗
PubMed1999

The role of sclerotherapy in abnormal varicose hand veins.

Large, tortuous veins involving the dorsa of the hands often become more prominent with the passage of time and are a common source of patient dissatisfaction. The objective was to evaluate the results of sclerotherapy in the management of unsightly varicose veins of the dorsum of the hand. From January of 1987 to August of 1998, 100 healthy, ambulatory female patients with a mean age of 56.5 years (range, 35 to 78 years) underwent sclerotherapy treatment for abnormally dilated veins on the dorsum of the hands. Patients were divided into two groups: group A consisted of 20 patients treated with 0.5% sodium tetradecyl sulfate (Sotradecol Elkins-Sin, Inc., Cherry Hill, N.J.) or 1.5% polidocanol (Aethoxysklerol Kreussler, Chemische-Fabrik, Wiesbaden, Germany). Group B consisted of 80 patients treated with 3% polidocanol. Postsclerotherapy compression was utilized in all cases. Failure was observed in 16 patients (80 percent) in group A. Successful elimination of varicose veins was obtained in 76 of 80 patients (95 percent) in group B. The diameter of treated vessels ranged from 1 to 6 mm (mean, 3 mm). Adverse events observed included pain, ecchymosis, various degrees of edema, and thrombosis of the treated veins. One patient (1 percent) developed transient neuropraxia of the superficial branch of the radial nerve following treatment of vessels located on the thenar web. Eleven of the 76 patients (14.5 percent) treated successfully with higher concentration developed microscopic neovascularization (matting). In conclusion, (1) low concentrations of sclerosing agents were associated with a high incidence of failure (80 percent); (2) the use of higher concentrations of polidocanol (3%) produced good results in 95 percent of treated patients; (3) adverse events common to sclerotherapy were observed in 90 percent of the treated patients-there were no serious adverse events; and (4) when appropriate sclerosant concentrations were employed, compression sclerotherapy proved to be an effective method of treatment for varicose veins involving the dorsum of the hand.

Adult↗
PubMed1998

Improving the intracellular delivery and molecular efficacy of antisense oligonucleotides in chronic myeloid leukemia cells: a comparison of streptolysin-O permeabilization, electroporation, and lipophilic conjugation.

The hybrid gene BCR-ABL that typifies chronic myeloid leukemia (CML) represents an attractive target for therapy with antisense oligodeoxyribonucleotides (ODN). A central obstacle in the therapeutic application of ODN is their poor cellular uptake. Adding various lipophilic conjugates to the ODN backbone has been reported to improve uptake, and electroporation of target cells has also been shown to enhance intracellular ODN delivery. We have shown that (1) BCR-ABL-directed ODN will specifically decrease the level of BCR-ABL mRNA, provided that cells are first permeabilized with Streptolysin-O (SL-O), and (2) chimeric methylphosphonodiester:phosphodiester ODN directed against 9 bases either side of the BCR-ABL junction are more efficient ODN effectors than structures composed solely of phosphodiester or phosphorothioate linkages. In this study, we compared the efficacy of lipophilic conjugation, SL-O permeabilization and electroporation on the intracellular delivery and molecular effect of BCR-ABL-directed ODN. b2a2- and b3a2-directed chimeric ODN were synthesized either unmodified or with one of the following groups at the 5' end: cholesterol, vitamin E, polyethylene glycol of average molecular weight 2,000 or 5,000, N-octyl-oligo-oxyethylene, or dodecanol. ODN associated with Lipofectin was also studied. Comparison was made in untreated, electroporated, and SL-O permeabilized KYO1 cells. Uptake was examined by fluorescence microscopy and flow cytometry, using ODN structures that were 3' labeled with fluorescein. The effect on target BCR-ABL mRNA expression was analyzed by Northern blotting. Several conjugated structures associated avidly with the cell membrane without achieving significant intracellular uptake or molecular effect. Similarly, ODN:Lipofectin complexes moderately increased cell association, without enhancing intracellular levels of ODN or inducing detectable molecular effect. In SL-O permeabilized or electroporated cells, uptake was approximately 1 to 2 logs greater than in untreated cells, and rapid nuclear localization was seen, especially with unmodified chimeric ODN. In SL-O permeabilized cells treated with ODN directed to the b2a2 and b3a2 junctions respectively, b2a2 BCR-ABL mRNA levels at 4 hours were reduced to 2. 6% +/- 2.1% and 38.4% +/- 1.3% of control values. In cells permeabilized by electroporation, BCR-ABL mRNA levels were decreased to 4.0% +/- 1.4% of control levels by b2a2 directed ODN, although very little nontargeted suppression was seen with b3a2-targeted ODN (93.4% +/- 4.2% of control). Greater cell to cell variation in ODN uptake was seen for SL-O permeabilized cells when compared with electroporated cells, suggesting that, after SL-O permeabilization, relatively unpermeabilized and overpermeabilized populations may coexist. No structure had any effect on the level of irrelevant (p53, MYC, and GADPH) mRNA levels. We conclude that the conjugation of chimeric ODN with one of the above-mentioned lipophilic groups or the complexing of ODN with Liopfectin does not improve either intracellular delivery of ODN or the molecular effect. In contrast, both electroporation and SL-O permeabilization (1) considerably enhanced uptake of chimeric ODN (even for structures without a conjugate group) and (2) achieved significant suppression of target mRNA levels.

Bacterial Proteins↗
PubMed1998

Classical conditioning and brain systems: the role of awareness.

Classical conditioning of the eye-blink response, perhaps the best studied example of associative learning in vertebrates, is relatively automatic and reflexive, and with the standard procedure (simple delay conditioning), it is intact in animals with hippocampal lesions. In delay conditioning, a tone [the conditioned stimulus (CS)] is presented just before an air puff to the eye [the unconditioned stimulus (US)]. The US is then presented, and the two stimuli coterminate. In trace conditioning, a variant of the standard paradigm, a short interval (500 to 1000 ms) is interposed between the offset of the CS and the onset of the US. Animals with hippocampal lesions fail to acquire trace conditioning. Amnesic patients with damage to the hippocampal formation and normal volunteers were tested on two versions of delay conditioning and two versions of trace conditioning and then assessed for the extent to which they became aware of the temporal relationship between the CS and the US. Amnesic patients acquired delay conditioning at a normal rate but failed to acquire trace conditioning. For normal volunteers, awareness was unrelated to successful delay conditioning but was a prerequisite for successful trace conditioning. Trace conditioning is hippocampus dependent because, as in other tasks of declarative memory, conscious knowledge must be acquired across the training session. Trace conditioning may provide a means for studying awareness in nonhuman animals, in the context of current ideas about multiple memory systems and the function of the hippocampus.

Aged↗
PubMed1998

Selecting optimal oligonucleotide composition for maximal antisense effect following streptolysin O-mediated delivery into human leukaemia cells.

It is widely accepted that most cell types efficiently exclude oligonucleotides in vitro and require specific delivery systems, such as cationic lipids, to enhance uptake and subsequent antisense effects. Oligonucleotides are not readily transfected into leukaemia cell lines using cationic lipid systems and streptolysin O (SLO) is used to effect their delivery. We wished to investigate the optimal oligonucleotide composition for antisense efficacy and specificity following delivery into leukaemia cells using SLO. For this study the well characterised chronic myeloid leukaemia cell line KYO-1 was selected and oligonucleotides (20mers) were targeted to an empirically identified accessible site of c- myc mRNA. The efficiency and specificity of antisense effect was measured 4 and 24 h after SLO-mediated delivery of the oligonucleotides. C5-propyne phosphodiester and phosphorothioate compounds were found to present substantial non-specific effects at 20 microM but were inactive at 0.2 microM. Indeed, no antisense-specific effect was noted at any concentration at either time. All of the other oligonucleotides tested induced some measurable antisense effect, except 7 (chimeric, all-phosphorothioate, 2'-methoxyethoxy termini) which was essentially inactive at 20 microM. The rank efficiency order of the remaining antisense compounds was 4 = 3 >> 9 >> 10 = 8 = 5 = 6 > 11. The efficient antisense effects induced by the chimeric methylphosphonate-phosphodiester compounds were found to be highly specific. Increased phosphorothioate content in the oligonucleotide backbone correlated with reduced antisense activity (efficacy: 2'-methoxyethoxy series 9 >> 8 >> 7, 2'-methoxytriethoxy series 10 > 11). No consistent evidence was obtained for increased activity correlating with increased oligonucleotide-mRNA heteroduplex thermal stability. In conclusion, the chimeric methylphosphonate-phosphodiester oligodeoxynucleotides present the most favourable characteristics of the compounds tested, for efficient and specific antisense suppression of gene expression following SLO-mediated delivery.

Bacterial Proteins↗
PubMed1998

Benefits and costs of supported employment from three perspectives.

Administrators, consumers, and policy makers are increasingly interested in supported employment as a way of helping persons with severe mental illness get and keep competitive jobs. However, in an atmosphere of increased expectations for performance and declining public financing, administrators want to know the costs and benefits of different approaches before they reallocate scarce treatment or rehabilitative dollars. This article discusses the net benefits of two approaches to supported employment that were compared in a randomized trial: Individual Placement and Support (IPS) and Group Skills Training (GST). The authors analyze costs and benefits from societal, government, and consumer perspectives. Although a previous analysis showed that IPS participants were significantly more likely to find work, worked more hours, and had higher earnings, net benefits of the two programs were not significantly different. The authors also discuss some of the strengths and weaknesses of cost-benefit analysis in mental health care and suggest future directions for policy and research.

Adult↗
PubMed1998

Desmoglein in multiple self-healing squamous epithelioma of Ferguson-Smith--comparison of staining patterns with actinic keratoacanthoma and squamous cell carcinoma of the skin.

BACKGROUND: Multiple self-healing squamous cell epithelioma of the skin (MSSE) is the most common variant of multiple keratoacanthoma. Although the morphology of the lesions in MSSE is similar to classical actinic keratoacanthoma (KA), several distinctive features in clinical presentation and histology have been emphasized. Desmosomes have been shown to be downregulated in certain types of carcinoma. Desmogleins (Dsg) are transmembrane desmosomal glycoproteins that exist as three isoforms. Dsg markers have been found to be reduced or absent in squamous cell carcinoma (SCC) but preserved in KA. OBJECTIVE: This study was designed to determine the pattern of Dsg staining in MSSE. METHODS: Eight tumors from two female patients with MSSE were stained with the antidesmoglein monoclonal antibody 32-2B, which recognizes Dsgl and Dsg3. RESULTS: All eight tumors showed uniform pericellular Dsg staining throughout the nonkeratinized layers of the neoplastic epithelium. This pattern is entirely similar to that observed in actinic KA, normal epidermis or follicular epithelium. CONCLUSION: Despite the differences, uniform preservation of Dsg seems to be the invariable feature of both MSSE and KA. Further studies are necessary to evaluate this antibody in routine dermatopathology of MSSE and SCC.

Aged↗
PubMed1998

Nail surgery.

Nail deformities may present as wither medical or cosmetic problems, often requiring surgical intervention. These deformities have a number of etiologic factors including infections, inflammatory disease processes, congenital abnormalities, trauma, tumors, and systemic diseases. This article discusses several nail problems and surgery techniques.

Bandages↗
PubMed1998

Trace eyeblink classical conditioning in the monkey: a nonsurgical method and behavioral analysis.

Classical eyeblink conditioning has been used extensively to study the neurobiology of associative learning and memory in rabbits and in humans. During the last several years, new developments have renewed interest in the possibility of studying classical conditioning in monkeys. Specifically, it is now known that impaired conditioning can be observed in humans with various neurologic problems, including amnesia, and thus there is now considerable interest in the neurobiology of human eyeblink conditioning. Research involving monkeys, in which discrete lesions of anatomically defined neural structures can be produced, has the potential to provide information that might not be readily available from work in humans. Here, the authors present a simple, nonsurgical method for classically conditioning the eyeblink response in monkeys and report behavioral results using a trace conditioning paradigm that is sensitive to hippocampal damage in both rabbits and humans. This method is reliable and effective for recording eyeblinks and shows that robust eyeblink classical conditioning can be readily established in the monkey.

Analysis of Variance↗
PubMed1998

Assertive community treatment for patients with co-occurring severe mental illness and substance use disorder: a clinical trial.

Integrated mental health and substance abuse treatment within an assertive community treatment (ACT) approach was compared to that within a standard case management approach for 223 patients with dual disorders over three years. ACT patients showed greater improvements on some measures of substance abuse and quality of life, but the groups were equivalent on most measures, including stable community days, hospital days, psychiatric symptoms, and remission of substance use disorder.

Adult↗
PubMed1998

Methodological issues in assertive community treatment studies.

Recent evaluations of ACT programs have produced equivocal findings, often leading to the invocation of methodological problems as responsible for the lack of positive results. This paper discusses issues of theory and methodology as they pertain to improving research of ACT, with particular attention paid to issues of sampling, process evaluation, measurement, and data analysis.

Bias↗