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Biomedical subjects

R E Clark

Publications and source records attributed to R E Clark.

At least 109 records · Page 6Linked to original sources
PubMed1996

Dermatofibrosarcoma protuberans treated with Mohs surgery. A case with CD34 immunostaining variability.

BACKGROUND: Immunohistochemical stains for CD34 antigen can help in differentiating dermatofibrosarcoma protuberans (DFSP) from other fibrohistiocytic tumors and in demarcating its surgical margins during Mohs surgery. However, variable expression of CD34 antigen in nodular areas can sometimes result in negative staining of tissue sections creating diagnostic and therapeutic dilemmas. OBJECTIVE: To show the variable expression of CD34 antigen in a DFSP tumor. METHODS: Case presentation of DFSP with immunohistochemical staining using the ABC peroxidase macromolecular complex. RESULTS: Microscopic examination of paraffin-embedded sections showed CD34-negative DFSP tumor cells with positive staining of endothelial cells. On frozen sections at the time of surgery the tumor cells stained strongly positive for CD34. CONCLUSION: This case demonstrates the variable expression of CD34 antigen by DFSP tumors and emphasizes the need to interpret with caution the results of these immunostains during Mohs surgery.

Adult↗
PubMed1996

Measuring hospital use without claims: a comparison of patient and provider reports.

OBJECTIVE: We compared the validity of hospital admission and length of stay reports from patients, outpatient providers, and hospitals, and we examined possible sources of error. DATA SOURCES: Data were collected from people enrolled in a randomized trial of treatment for severe mental illness and substance use disorders, from community mental health centers (CMHCs), and from hospitals. Reports for each of the 74 study participants covered two-year time periods beginning and ending at various times between 1989 and 1993. STUDY DESIGN: We compared reports from the various sources and constructed a hybrid with data from all three sources. Using parametric and non-parametric statistics, we compared patient, CMHC, and hospital reports with each other and with the hybrid source. In subsequent regression analyses we explored correlates of reporting accuracy. PRINCIPAL FINDINGS: Single-source reports underestimated hospital use, but when patient and CMHC reports were combined, results were very similar to those obtained by the more laborious hybrid method. Patient reports became less accurate as the time between discharge and reporting increased; people with bipolar disorders reported admissions with greater accuracy than did people with schizophrenia. CMHC reporting accuracy decreased as the distance to the admitting hospital increased and were less accurate for people with more severe psychiatric symptoms. CONCLUSIONS: Reports from single sources are likely to underestimate hospital use for different reasons. Combining carefully collected data from patients and outpatient providers produces estimates of hospital use that are substantially the same as those developed through methods that are more laborious and costly.

Adult↗
PubMed1996

The influence of class II HLA type on the lymphoproliferative response of normal donors to a bcr-abl fusion peptide.

Chronic myelogenous leukemia (CML) is characterized by a t(9;22) chromosomal translocation resulting in the expression of a novel bcr-abl fusion protein. The region spanning the fusion point is novel to the immune system and hence represents a potential leukemia-specific antigen. The ability of a 21-mer b3a2 fusion peptide to induce an in vitro lymphoproliferative response in a panel of 54 normal donors has been tested. This gave a mean stimulation index of 2.73 (95% CI 2.42-3.05) and 50/54 (93%) of donors gave responses that were greater than those with bcr or abl control peptides. The mean stimulation index relative to that of the control peptides was 1.80 (95% CI 1.63-1.97; p < 0.001). Responses were optimal at concentrations ranging from 0.3-150 micrograms/mL and in most cases peaked at 9 days. There was no clear relationship between level of responsiveness to the b3a2 fusion peptide and the presence of any single HLA-A, -B, -DR, or -DQ allele. HIA-DRB1*0404 was the only allele that was not associated with responsiveness. It is therefore likely that the b3a2 fusion peptide can be presented to T cells during a primary immune response in the context of several different class II HLA allelic products, albeit at low efficiency. The implications for specific active immunotherapy of CML patients are discussed.

Alleles↗
PubMed1995

A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood loss and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting.

BACKGROUND: Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients. To examine the safety and dose-related efficacy of aprotinin, a prospective, multicenter, placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS: Two hundred eighty-seven patients were randomly assigned to receive either high-dose aprotinin, low-dose aprotinin, pump-prime-only aprotinin, or placebo. Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume. The percentage of patients requiring donor-red-blood-cell (RBC) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups (high-dose aprotinin, 54%; low-dose aprotinin, 46%; pump-prime only, 72%; and placebo, 75%; overall P = .001). The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo (high-dose aprotinin, 1.6 +/- 0.2 U; low-dose aprotinin, 1.6 +/- 0.3 U; pump-prime-only, 2.5 +/- 0.3 U; and placebo, 3.4 +/- 0.5 U; P = .0001). There was also a significant difference in total blood-product exposures among treatment groups (high-dose aprotinin, 2.2 +/- 0.4 U; low-dose aprotinin, 3.4 +/- 0.9 U; pump-prime-only, 5.1 +/- 0.9 U; placebo, 10.3 +/- 1.4 U). There were no differences among treatment groups for the incidence of perioperative myocardial infarction (MI). CONCLUSIONS: This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI.

Aged↗
PubMed1995

Optimization of antisense oligodeoxynucleotide structure for targeting bcr-abl mRNA.

Antisense oligodeoxynucleotides targeted to bcr-abl are potential ex vivo purging agents for use with autologous bone marrow transplantation in the treatment of chronic myeloid leukemia (CML). We investigated, in a cell-free system, the activity and nuclease resistance of phosphodiester, phosphorothioate, chimeric methylphosphonate/phosphodiester, and chimeric methylphosphonate/phosphorothioate antisense octadecamers directed against either b2a2 or b3a2 bcr-abl breakpoint RNAs. Certain chimeric compounds were shown to possess targeted activity broadly equal to the parent phosphodiester or phosphorothioate forms and greater resistance to the nucleases present in cell extracts. Selected chimeric structures were compared with phosphodiester and phosphorothioate analogues for antisense activity in human CML cells containing either b2a2 or b3a2 bcr-abl breakpoint mRNAs. We present results showing that all four structures can suppress bcr-abl mRNA level in vivo. The rank of in vivo activity is chimeric methylphosphonate/phosphodiester > or = phosphodiester > phosphorothioate > methylphosphonate/phosphorothioate. We show that b2a2 breakpoint RNAs can be more effectively targeted than b3a2 sequence RNAs both in vitro and in vivo and suggest that RNA secondary structure may be a possible explanation for this phenomenon.

Base Sequence↗
PubMed1995

The STS Cardiac Surgery National Database: an update.

Since inception in 1990, The Society of Thoracic Surgeons (STS) National Cardiac Database has grown rapidly. More than 1,500 surgeons working in 706 hospitals have contributed more than one half million patient records. Geographic distribution of those participating is proportional to the number of centers performing heart surgery. The STS system is in use in all 49 states where centers are operating. There has been a significant decrease in length of stay for most patients having heart operations and a modest fall in coronary artery bypass grafting operative mortality from 3.7% to 3.3% over the past 3 years. Coronary artery bypass grafting case mix also is changing nationally as evidenced by a decline of 17% in the best-risk cases and concomitant increases in those with predicted risks of 5% to 10% and greater. New uses for local data in addition to self assessment and quality assurance include development of critical clinical pathways, support for managed-care group applications, and regional use. Minnesota has established a statewide STS system and Florida is soon to follow. The key to acceptance has been a peer-reviewed risk-stratification system that continues to be refined each year. Finally, a major effort will be made this year to increase the participation of general thoracic surgeons, particularly with respect to lung cancer.

Cardiac Surgical Procedures↗
PubMed1995

Immunohistochemical techniques in Mohs micrographic surgery: their potential use in the detection of neoplastic cells masked by inflammation.

BACKGROUND: Histopathologic evaluation of tissue obtained from Mohs micrographic surgery is the key step in obtaining complete tumor removal. Residual undetected tumor may result in recurrence. OBJECTIVE: In circumstances in which the histopathologic interpretation is difficult, we assessed the potential use of immunohistochemical techniques to detect tumor in Mohs micrographic surgical specimens. METHODS: A rapid immunoperoxidase technique with monoclonal anticytokeratin antibodies was performed on Mohs frozen sections. Cases selected included morpheaform basal cell carcinomas, perineural tumors, and sections with dense inflammation without apparent tumor. RESULTS: Four cases are described as examples that highlight the potential usefulness of immunostaining of Mohs tissue sections. Anticytokeratin antibodies helped to confirm free tumor margins, thus avoiding the unnecessary sacrifice of normal tissue, and to delineate tumor not identified in hematoxylin and eosin frozen sections. CONCLUSION: Immunohistochemical staining of Mohs micrographic surgical specimens with anticytokeratin antibodies is particularly useful when dense inflammatory infiltrate is present, because the latter may obscure any residual tumor. Application of this technique to difficult cases may prevent tumor recurrences or unnecessary excision of normal tissue.

Aged↗
PubMed1995

Human recombinant stem-cell factor induces melanocytic hyperplasia in susceptible patients.

BACKGROUND: Recombinant human stem-cell factor (SCF), a cytokine acting on hematopoietic progenitor cells, has potential for the treatment of several hematologic and oncologic disorders. In a hematology-oncology phase I trial of SCF, several patients had cutaneous hyperpigmentation at the SCF subcutaneous injection sites. OBJECTIVE: Our purpose was to investigate the pathogenesis of this hyperpigmentation phenomenon. METHODS: Skin biopsy specimens were obtained before, at the completion of, and after SCF therapy and were processed for histology, immunohistology, and electron microscopy. RESULTS: Skin at the site of SCF injection had an increased number of melanocytes, increased melanocytic dendrite extension, and melanin as compared with noninjected tissue. Immunohistochemical stains revealed an increase in staining with melanocyte-specific monoclonal antibodies HMB-45 and NKI/beteb, and a monoclonal antibody to the receptor for SCF, c-kit. CONCLUSION: Subcutaneous injection of SCF results in hyperplasia of melanocytes. SCF may be useful in the treatment of melanocytopenic disorders, but caution may be necessary in patients with disorders of melanocyte proliferation.

Antibodies, Monoclonal↗
PubMed1995

Lymphoepithelioma-like carcinoma of the skin treated with Mohs micrographic surgery in combination with immune staining for cytokeratins.

Lymphoepithelioma-like carcinoma of the skin (LLCS) is a rare cutaneous neoplasm that histologically resembles nasopharyngeal lymphoepithelioma. Conventional surgical excision carries a considerable rate of recurrence (three of 11 reported cases with such treatment, with one patient dying of metastatic disease). We report the first case of lymphoepithelioma-like carcinoma of the skin treated with Mohs micrographic surgery. Because of its tendency to occur on the face and its potential for recurrence after incomplete removal, this tumor is a good candidate for treatment with Mohs micrographic surgery. Immunohistochemical staining of frozen sections for cytokeratins may help to detect neoplastic cells that may be obscured by the dense lymphoplasmacytic infiltrate associated with this tumor.

Aged↗
PubMed1995

Clinical study of location and reproducibility of three mandibular positions in relation to body posture and muscle function.

Clinical studies have confirmed the adequate reproducibility of both centric occlusion and centric relation when used as reference positions during treatment; however, the reproducibility of the neuromuscular position has been found inadequate. This study evaluated the location and reproducibility of these three mandibular positions in relation to body posture, sitting and supine, and bilateral muscle activity before and after the insertion of a flat mandibular positioning device equilibrated to balance the muscle functions, as shown by two electromyography biofeedback instruments. Intraoral recordings were made in 11 young subjects with complete natural dentition. Acrylic resin clutches that supported a screw point in the maxillary arch and painted glass in the mandibular arch were used and positioned not to interfere with the occlusion. The distances of the screw scratch from two of the edges of the painted glass were used to measure the anteroposterior and mediolateral locations with a micrometer. The reproducibility was evaluated by measuring the scratch surface by measuring the weight of the print cutouts made from photographs of the scratches taken with a stereoscope. The location and reproducibility of centric occlusion and centric relation were not affected by body posture. A more precise posterior neuromuscular position was obtained in the supine position. The insertion of a mandibular positioning device did not affect centric occlusion but gave a more precise centric relation. Neuromuscular position became as precise as centric occlusion and was located anteroposteriorly between centric occlusion and centric relation.

Acrylic Resins↗
PubMed1995

Microemboli during coronary artery bypass grafting. Genesis and effect on outcome.

Cerebral dysfunction after coronary artery bypass operations represents some of the most serious and costly complications of cardiac surgery. We used transcranial Doppler ultrasonography to detect and quantify the number of microemboli in the right middle cerebral artery of patients undergoing elective first coronary bypass operations (n = 117) and second coronary bypass operations (n = 10). We hypothesized that total microemboli were related to clinical outcome. A 2 MHz transducer was positioned in front of the ear above the zygomatic arch and depth gated to 50 mm. Microemboli were recorded as perturbations of the blood flow velocity in the middle cerebral artery and aurally monitored. Each episode of microembolism was specified both by clock time and as a perfusion or surgical event. Forty-one patients (32%) completed neuropsychologic evaluation with a battery of tests for cognitive function. Anxiety states and traits were also assessed. The distribution of microembolism showed that there were three groups of patients: < 30 microemboli (n = 83); 30 to 59 (n = 24); and > 60 (n = 20). Seven of 10 patients with cerebral complications (stroke, coma, delirium, aberrant behavior) were in the > 60 microemboli group. Those with cerebral complications had 20.7 +/- 4.5 microemboli from perfusion and 57.4 +/- 15.6 from surgical events. The 13 patients in the > 60 microemboli group without central nervous system symptoms had 95.5 +/- 19.5 microemboli from perfusion and 36.0 +/- 6.9 from surgical events. Neuropsychologic scores were most often depressed for memory (73%), comprehension (49%), attention (46%), and constructional ability (44%). The greatest change was in total score in the > 60 microemboli group (-3.3 +/- 0.6) compared with -1.1 +/- 0.2 and -1.9 +/- 0.2 for the 30 to 59 and < 30 groups, respectively. The incidences of cardiac and pulmonary complications and mortality were different between those patients with < 60 microemboli versus those with > 60 microemboli. Cardiac and pulmonary complications and mortality percentages were 4.7%, 3.7%, and 0.9%, respectively, for the < 60 microemboli group and 20%, 20%, and 15%, respectively, for the > 60 microemboli group. We concluded that transcranial Doppler ultrasonography is a useful technique to quantify and detect the source of microemboli during coronary artery bypass operations and may be useful in assessing new operative strategies, the quality of the perfusion, and potentially as an indicator for pharmacologic therapy in the operating room in patients with high microemboli counts.

Cardiopulmonary Bypass↗
PubMed1995

Hippocampectomy impairs the memory of recently, but not remotely, acquired trace eyeblink conditioned responses.

New Zealand male rabbits (Oryctolagus cuniculus) were trained on a trace eyeblink conditioning paradigm using a 250-ms tone conditioned stimulus, a 100-ms airpuff unconditioned stimulus, and a 500-ms trace interval. Rabbits received bilateral hippocampal aspirations either 1 day or 1 month after learning. Controls consisted of time-matched sham-operated and neocortical aspirated rabbits. When retested on the trace paradigm, rabbits with hippocampal aspirations 1 day after learning were significantly and substantially impaired in the retention of trace conditioned responses. In contrast, rabbits that received hippocampal aspirations 1 month after training retained trace conditioned responses at a level comparable to that of the controls. Moreover, hippocampectomy had no effect on the retention of delay eyeblink conditioning. Thus, the hippocampus appears to be necessary for the retention of recently acquired, but not remotely acquired, trace conditioned responses.

Animals↗
PubMed1995

Severe hypophosphataemia during stem cell harvesting in chronic myeloid leukaemia.

Peripheral blood stem cell autografts for the treatment of chronic myeloid leukaemia (CML) are currently under evaluation. A patient with CML received intensive chemotherapy followed by granulocyte colony-stimulating factor prior to the collection of peripheral blood derived stem cells. He developed unusually severe, and fatal, hypophosphataemia and this coincided with the rapid rise of his peripheral blood white cell count. The hypophosphataemia was considered to be due to a combination of severe anorexia, sepsis and the rapid growth factor-stimulated myeloid regeneration in CML.

Adult↗
PubMed1995

Distribution of CD44 variant isoforms in human skin: differential expression in components of benign and malignant epithelia.

Expression of cell adhesion molecules regulates epithelial cell differentiation and organization of complex tissues such as skin. The CD44 family of adhesion molecules is generated by alternative splicing of up to 10 variant exons encoding inserts into the extracellular domain. Expression of CD44 variant exons has been correlated with metastatic potential of some epithelial malignancies. We studied the distribution of total and variant CD44 isoforms containing exons v4, v6, and v9 in normal skin, basal cell carcinoma, and in control tissues using immunohistologic assays. While normal epidermis and other stratified squamous epithelia reacted strongly with antibodies specific for standard CD44 (CD44S) and CD44 isoforms containing exons v4, v6, and v9, the epithelium of eccrine glands was reactive, often in a polarized distribution, only with antibodies specific for CD44S and isoforms containing exon v9. These studies suggest that differential expression of CD44 variant exons may be important in development and organization of epithelial structures within skin. Malignant cells in basal carcinoma tissues were found to have low reactivity with antibodies specific for CD44S or variant CD44 molecules. The low expression of CD44 molecules in basal cell carcinomas may play a role in the relatively low probability of metastasis of these neoplasms.

Antibodies, Monoclonal↗
PubMed1995

Increased middle cerebral artery flow velocity during the initial phase of cardiopulmonary bypass may cause neurological dysfunction.

One hundred twenty-seven patients undergoing coronary artery bypass graft surgery were monitored by transcranial Doppler ultrasonography. Five patients had more than 50% increases in middle cerebral artery mean flow velocity during the initial phase (10-120 sec) of cardiopulmonary bypass. Four of these 5 developed neurological complications including stroke and encephalopathy. These results indicate that overperfusion of the basal cerebral arteries during cardiopulmonary bypass procedures may contribute to neurological dysfunction after the surgery.

Adult↗
PubMed1995

Poor cellular uptake of antisense oligodeoxynucleotides: an obstacle to their use in chronic myeloid leukaemia.

The molecular effect of the Philadelphia translocation typical of over 90% of chronic myeloid leukaemia (CML) patients is to create a novel hybrid gene, bcr-abl. The mRNA transcript of this CML-specific gene has only 2 alternative sequences, designated b3a2 and b2a2. Short oligodeoxynucleotide (ODN) sequences complementary (or antisense) to the bcr-abl junction may have potential as leukaemia-specific therapy. However, the studies on ODN targeting bcr-abl reported so far have used ODN linked by either phosphodiester or phosphorothionate linkages. Both of these ODN structures have drawbacks as potential therapeutic agents (nuclease sensitivity, non-specific effects). In contrast, ODN linked by a mixture of methylphosphonate and conventional linkages can mediate cleavage of bcr-abl mRNA target in a sequence-specific fashion, unlike conventionally linked ODN. Poor ODN uptake into intact cells remains a central difficulty for all ODN structures. Several strategies to improve cellular uptake of ODN are under current investigation.

Base Sequence↗
PubMed1995

Incentives for community treatment. Mental illness management services.

Serving people with mental and other chronic illnesses in community settings may improve compliance and satisfaction with treatment, but existing payment mechanisms often favor office-based treatment. This study examines the effect of a change in Medicaid payment on the location and amount of service provided by case managers. Amounts of service given by treatment providers to 185 of their clients in community settings and in mental health centers were compared before and after reimbursement changed from an all-inclusive prospective rate to a mixed prospective/retrospective payment. Clients were enrolled in two different treatment programs: continuous treatment teams with extensive training in in vivo treatment, and a case management program that emphasized office-based treatment. In-community service increased, and the amount of office-based treatment decreased. Continuous treatment teams increased in-community services more than case managers did; case managers decreased office-based treatment more. There was no change in total amount of services provided. It was concluded that mixed prospective and retrospective reimbursement can remove financial barriers to in-community treatment, but it works best in combination with a training program. Additional research is needed to determine the precise financial impact of such changes.

Adult↗