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Biomedical subjects

M Carter

Publications and source records attributed to M Carter.

At least 73 records · Page 4Linked to original sources

The incidence of prostate cancer progression with undetectable serum prostate specific antigen in a series of 394 radical prostatectomies.

PURPOSE: Serum prostate specific antigen (PSA) has been reported to be a sensitive indicator of recurrent carcinoma after radical prostatectomy but it is not absolute. Disease progression with undetectable PSA levels has been described but the incidence of this phenomenon is unknown. MATERIALS AND METHODS: We retrospectively analyzed the records of 394 consecutive men who underwent radical prostatectomy between 1980 and 1991 to characterize the incidence of recurrent carcinoma despite undetectable serum PSA levels. RESULTS: Of the 394 men 133 had documented evidence of disease recurrence, 3 (2.3%) despite undetectable serum PSA levels (2 had local and systemic evidence of disease progression). Histological dedifferentiation characterized these recurrences. CONCLUSIONS: Although a post-prostatectomy detectable serum PSA level precedes clinical evidence of disease progression by years, rare patients (2.3% in our series) in whom recurrent disease is characterized by marked histological dedifferentiation will remain negative for PSA.

Aged↗

The electronic patient record: a strategic planning framework.

Sunnybrook Health Science Center (Sunnybrook) is a multifacility academic teaching center. In May 1994, Sunnybrook struck an electronic patient record taskforce to develop a strategic plan for the implementation of a comprehensive, facility wide electronic patient record (EPR). The taskforce sought to create a conceptual framework which provides context and integrates decision-making related to the comprehensive electronic patient record. The EPR is very much broader in scope than the traditional paper-based record. It is not restricted to simply reporting individual patient data. By the Institute of Medicine's definition, the electronic patient record resides in a system specifically designed to support users through availability of complete and accurate data, practitioner reminders and alerts, clinical decision support systems, links to bodies of medical knowledge, and other aids [1]. It is a comprehensive resource for patient care. The taskforce proposed a three domain model for determining how the EPR affects Sunnybrook. The EPR enables Sunnybrook to have a high performance team structure (domain 1), to function as an integrated organization (domain 2), and to reach out and develop new relationships with external organizations to become an extended enterprise (domain 3) [2]. Domain 1: Sunnybrook's high performance teams or patient service units' (PSUs) are decentralized, autonomous operating units that provide care to patients grouped by 'like' diagnosis and resource needs. The EPR must provide functions and applications which promote patient focused care, such as cross functional charting and care maps, group scheduling, clinical email, and a range of enabling technologies for multiskilled workers. Domain 2: In the integrated organization domain, the EPR should facilitate closer linkages between the arrangement of PSUs into clinical teams and with other facilities within the center in order to provide a longitudinal record that covers a continuum of care. Domain 3: In the inter-enterprise domain, the EPR must allow for patient information to be exchanged with external providers including referring doctors, laboratories, and other hospitals via community health information networks (CHINs). Sunnybrook will prioritize the development of first domain functionality within the corporate constraints imposed by the integrated organization domain. Inter-enterprise computing will be less of a priority until Sunnybrook has developed a critical mass of the electronic patient record internally. The three domain description is a useful model for describing the relationship between the electronic patient record enabling technologies and the Sunnybrook organizational structures. The taskforce has used this model to determine EPR development guidelines and implementation priorities.

Medical Records Systems, Computerized↗

A surgical process management tool.

Inspired by a shortage of qualified nursing personnel at local facilities, a group of University of Toronto researchers has created a simulation based decision support tool that enables hospitals to determine the overall effect of making modifications to operating room schedules, as well as a number of other system parameters, including the number of inpatient beds and the amount of nursing time available on surgical wards.

Appointments and Schedules↗

Adapting symptom validity testing to evaluate suspicious complaints of amnesia in medicolegal evaluations.

Symptom validity testing was adapted to assess suspicious complaints of amnesia. In the adaptation, two-alternative, forced-choice memory questions were generated for subject matter claimed to be forgotten. The number of questions correctly answered was then compared to the expected number of questions to be correctly answered if no knowledge actually existed. Three case studies are presented, two of competency-to-stand-trial evaluees and one of an insurance medical examinee. In each case, the use of this procedure generated the conclusion that the knowledge claimed to be forgotten was actually remembered; however, not all individuals were classified as malingerers.

Accidents, Traffic↗

Prevalence and clinical correlations of MLL gene rearrangements in AML-M4/5.

Rearrangements of the human trithorax gene (MLL, HRX, Htrx-1, All-1) were studied by Southern blotting in blast cells stored at presentation from 65 adults with de novo acute myelomonocytic (AML-M4) and acute monocytic leukemia (AML-M5). MLL rearrangements were demonstrated in 15 (23%) cases, including eight patients in whom karyotype analysis had failed to detect abnormalities of chromosome band 11q23. The patients with MLL rearrangements did not differ significantly from those with germline configurations in terms of the sex and age of the patients, the presence of lymphadenopathy, hepatosplenomegaly, or central nervous system involvement, and the absolute blast count at diagnosis. Kaplan-Meier analysis of the treated patients demonstrated no difference in survival for patients with MLL rearrangements compared with those without rearrangements. Therefore, in contrast to infantile acute leukemia, in adults with AML-M4 and AML-M5, MLL rearrangements do not identify a subgroup of patients with different clinical features or prognosis.

Adolescent↗

Fragile X induction systems in CVS cultures: effect on cytogenetic, PCR, and genomic Southern Blot DNA analyses of the FMR-1 gene.

Low fragile X frequencies have been commonly observed in chorionic villus sample (CVS) cultures, compared to subsequent analysis in whole blood or products of conception (POC). To investigate possible mechanisms for this effect, CVS cultures from a previously identified fragile X positive male, were restudied and compared to subsequent POC cultures from lung, muscle, skin, and thymus. Cultures were exposed, for the last 24 hours before harvesting, to FUdR, excess thymidine, and a combination of both. For CVS, only those cultures that were exposed to a combination of FUdR and excess thymidine showed positive cytogenetic findings (1/90 or 1.1%), agreeing with our original positive cytogenetic results (2/86 or 2.3%) for cultures exposed to excess thymidine. Fragile X frequencies in the POC tissues from this fetus increased to an average of 14%. PCR analyses showed full mutations (> 200 CGG repeats) in uninduced CVS cultures but induced cultures exhibited apparently smaller sizes in the range of 120-180 repeats. The results showed variability. In one instance, the banding pattern from one of the uninduced cultures was similar to the results where cultures were exposed to a double induction system. When PCR analyses were conducted on induced POC cultures, full mutations were observed in virtually all samples. Southern blot genomic analysis using probe StB12.3 showed an unmethylated full mutation in CVS cultures. Southern blot patterns from cultures of muscle revealed size variations of DNA bands in the premutation range representing unmethylated DNA as well as methylated full mutations. Finally, variations were also observed in lung and skin cultures, compared to CVS and muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Southern↗

Chronic adenosine A1 receptor agonist and antagonist: effect on receptor density and N-methyl-D-aspartate induced seizures in mice.

The effect of chronic administration of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on N-methyl-D-aspartate (NMDA)-evoked seizures was studied in C57BL/6 mice (20/group). Animals were injected i.p. for 9 days with either 1.0 mg/kg CPA or 1.0 mg/kg CPX followed by 2 injection-free days (the washout period) and subsequent administration of a single dose of 60 mg/kg NMDA. As in our previous study, this dose of NMDA caused clonic/tonic seizures resulting in high (60%) mortality within 3 h after injection of the drug. Despite insignificant changes in seizure latency, chronic pretreatment with CPA increased the incidence of clonic/tonic episodes and end-point mortality. Conversely; chronic exposure to CPX completely eliminated clonic/tonic episodes, significantly increased average survival time, and reduced end-point mortality (P < 0.05). The results indicate that chronic treatment with adenosine A1 receptor antagonist may protect against NMDA-evoked seizures to the same degree as previously observed following a single, acute exposure to CPA. Since the density of adenosine receptor binding sites was unchanged after chronic treatment with either CPX or CPA, it is likely that the mechanism behind the observed protection may rest at the level of second messenger systems coupled to adenosine A1 receptors.

Adenosine↗

Nap studies underestimate the incidence of gastroesophageal reflux.

Shorter nap (1 and 4 hr) pH studies inaccurately diagnosed gastroesophageal reflux (GER) in a group of infants evaluated for apparent life threatening events (ALTE) and recurrent apnea. Twenty-five infants with a postconceptional age of 42 +/- 8 SD weeks, were evaluated by 12-hr polysomnography (PSG). Prior to the start of the 12-hr study, a 1-hr Tuttle Test was performed. By means of the 12-hr study 11 infants were diagnosed as having GER while the Tuttle Test incorrectly diagnosed 6 infants, 5 as having no GER and 1 as having GER when no GER was present (P < 0.05). No differences in the amount of periodic breathing (PB) or apnea density (AD) were found between the two studies. In addition, the first 4 hr of the 12-hr PSG segment following the first feeding was evaluated separately. In the 4-hr segment, two of the infants were incorrectly diagnosed as not having GER. In this study, nap studies failed to diagnose all of the infants with GER. Therefore, we conclude that an infant cannot be accurately diagnosed as not having GER without prolonged pH recording.

Female↗

Use of recombinant virus to assess human cytomegalovirus early and late promoters in the context of the viral genome.

We have developed a system to study human cytomegalovirus (HCMV) cis-acting promoter elements within the context of the viral genome. A recombinant HCMV (RV134) containing a marker gene (beta-glucuronidase) was used to insert HCMV promoter-chloramphenicol acetyltransferase gene constructs into the viral genome between open reading frames US9 and US10. Using this system, we have studied the promoters for the early DNA polymerase gene (UL54), the early-late lower matrix phosphoprotein gene (pp65, UL83), and the true late 28-kDa structural phosphoprotein gene (pp28, UL99). Transient-expression assays demonstrated that the pp65 and pp28 promoters are activated earlier and to higher levels than typically observed with the endogenous gene. In contrast, insertion of these promoters into the viral genome resulted in kinetics which mimicked that of the endogenous genes. In addition, we have also tested a variant of the pp28 promoter (d24/26CAT) which is deleted from -609 to -41. This promoter behaved similarly to the wild-type pp28 promoter, indicating that sequences from -40 to +106 are sufficient for conferring true late kinetics. Taken together, these data demonstrate that the viral genome affords a level of regulation on HCMV gene expression that has been previously unrealized. Therefore, these experiments provide a model system for the analysis of cis-acting promoter regulatory elements in the context of the viral genome.

Blotting, Southern↗

The comprehensive health enhancement support system.

This article describes the process of using needs assessment data to develop an interactive information technology specifically designed to support patients in a health-related crisis. The Comprehensive Health Enhancement Support System (CHESS) is an interactive information, social support, and problem-solving system that was developed by a team at the University of Wisconsin. This article looks at the program developed for breast cancer patients and their families.

Breast Neoplasms↗

Effects of N6-cyclopentyl adenosine and 8-cyclopentyl-1,3-dipropylxanthine on N-methyl-D-aspartate induced seizures in mice.

The effect of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on N-methyl-D-aspartate (NMDA)-evoked seizures was studied in C57BL/6 mice (20/group). Animals were injected i.p. either with CPA (0.5, 1, 2 mg/kg) or CPX (1, 2 mg/kg) 15 min prior to administration of NMDA (30, 60, 125 mg/kg). Administration of NMDA alone resulted in a complete locomotor arrest at 30 mg/kg, while clonic/tonic seizures and progressively increasing mortality were seen at higher doses. Prior administration of CPA resulted either in a delay of seizure onset and unchanged mortality (0.5 mg/kg CPA, 60 mg/kg NMDA) or in elimination of tonic episodes and a significant reduction in postictal mortality (1, 2 mg/kg CPA; 60, 125 mg/kg NMDA). Pretreatment with CPX at either 1 or 2 mg/kg eliminated locomotor depression in animals injected with NMDA at 30 mg/kg. At 60 mg/kg NMDA, the effect of CPX administration resulted in mortality equivalent to that seen with 125 mg/kg NMDA administered alone. The results indicate that A1 receptor agonists may protect against NMDA-evoked seizures and that the adenosine A1 receptor may be directly involved in these actions.

Adenosine↗

Typing of feline calicivirus isolates from different clinical groups by virus neutralisation tests.

One hundred and thirteen isolates of feline calicivirus originating from seven different clinical groups were typed by virus neutralisation tests using eight different cat antisera. The clinical groups comprised 'healthy' cats, cases of acute oral/respiratory disease, chronic stomatitis, acute febrile lameness syndrome, vaccine reactions (clinical disease seen within 21 days of vaccination) and vaccine breakdowns (clinical disease seen more than 21 days after but within one year of vaccination). Isolates from the vaccine reaction cases were grouped into those associated with acute oral/respiratory disease alone and those associated with the lameness syndrome, and the latter group was further subdivided according to the vaccine used. Two groups appeared significantly different from others with some of the antisera. Thus the lameness vaccine reaction isolates associated with vaccine B were significantly different from the isolates from all the other clinical groups, including other lameness isolates, with a number of the antisera. In addition, the chronic stomatitis isolates were significantly different from those from the 'healthy' and the acute oral/respiratory disease groups with one or two of the antisera. Eighty-five to 88 per cent of the isolates were neutralised by antisera raised against F9 or F9-like vaccine strains at a dilution of 1 in 2. Twenty antibody units of such antisera neutralised 42 to 80 per cent of the isolates. A bivalent antiserum raised against a vaccine F9 strain and field strain LS015 neutralised 96 per cent of the isolates at a dilution of 1 in 2, and 20 antibody units neutralised 68 per cent of isolates. Antisera to field strain F65 neutralised all the remaining isolates at a dilution of 1 in 2 and 44 per cent of the remaining isolates at a dilution of 20 antibody units. Therefore, strains LS015 and F65 may be of use in the production of a polyvalent feline calicivirus vaccine, together with the widely used strain F9.

Animals↗

Expression of Drosophila Rrp1 protein in Escherichia coli. Enzymatic and physical characterization of the intact protein and a carboxyl-terminally deleted exonuclease-deficient mutant.

Drosophila Rrp1 protein purified from embryos has four tightly associated enzymatic activities: DNA strand transfer, single-strand DNA renaturation, 3'-exonuclease, and apurinic endonuclease. Copurifying with these activities is a single polypeptide that has an apparent M(r) of 105,000 when estimated by SDS-polyacrylamide gel electrophoresis. To determine if this polypeptide is sufficient for these activities, it has been overexpressed in Escherichia coli. In crude extracts of E. coli cells, an ATP-independent Mg(2+)-dependent strand transfer activity is observed upon activation of the promoter that drives expression of Rrp1. Rrp1 protein purified from induced E. coli cells has electrophoretic, chromatographic, and enzymatic properties similar to those of Drosophila Rrp1 protein. The carboxyl-terminal region of Rrp1 (amino acids 428-679) is homologous to E. coli exonuclease III. Rrp1 deleted for this region cannot carry out DNA strand transfer, but can renature complementary single-strand DNA. The strand transfer activity of this truncated protein can be restored if DNA 3'-exonuclease is provided in trans by pretreating the double-strand DNA substrate with E. coli exonuclease III. This demonstrates a likely role of the exonuclease in the in vitro DNA strand transfer reaction carried out by Rrp1 protein. Such a role is also suggested by an analysis of the polarity of the strand transfer reaction.

Animals↗

Laser-assisted enterocystoplasty in rats.

The employment of laser welds to anastomose bowel to bladder in urological surgery has never been described. Using rats, we compared laser-assisted enterocystoplasty (LAE) with conventional sutured enterocystoplasty (CSE). A "patch" ileocystoplasty was performed using distal ileum. Operative time, intraluminal bursting pressure and histologic changes were evaluated. Operative time was 38% less in the LAE (p < 0.001). No statistically significant differences in bursting pressure between LAE and CSE groups was demonstrated (p = 0.654) in rats sacrificed 2 weeks postoperatively. Histologic findings in the laser-assisted enterocystoplasties included early loose granulation tissue and later organization of the granulation tissue with significant collagen deposition. In our preliminary study, laser welding of bowel within the urinary stream was safe, efficacious and rapid and resulted in a mechanically comparable surgical outcome.

Anastomosis, Surgical↗

Monoclonal antibodies of three different immunoglobulin G isotypes produced by immunization with a synthetic peptide or native protein protect mice against challenge with Plasmodium yoelii sporozoites.

Passive transfer of monoclonal antibodies (MAbs) against malaria circumsporozoite (CS) proteins protects animals against malaria. Active immunization with synthetic or recombinant peptides induces a level of polyclonal antibodies to sporozoites comparable to those found after passive immunization but does not provide comparable protection. In the Plasmodium yoelii system, synthetic or recombinant peptide-induced antibodies have never been shown to protect. The current studies were designed to determine whether immunogen structure (native protein versus synthetic peptide) or immunoglobulin G (IgG) subclass of antibodies was responsible for the absolute differences between protective, passively transferred MAbs and nonprotective, actively induced polyclonal antibodies. In this study we produced two MAbs, QGP-S1 (IgG1) and QGP-S2 (IgG2b), by immunization with a synthetic peptide based on the P. yoelii CS major repeat, (QGPGAP)4, conjugated to keyhole limpet hemocyanin. These MAbs were compared tp NYS1 (IgG3), an anti-CS protein MAb previously produced by immunization with irradiated P. yoelii sporozoites, which recognizes (QGP GAP)2. QGP-S1 and QGP-S2 passively transferred protection. However, when compared with NYS1, there was a hierarchy of protection, NYS1 > QGP-S1 > QGP-S2. There was no correlation between antibody level at challenge as determined by immunofluorescent antibody test against sporozoites or enzyme-linked immunosorbent assay against (QGPGAP)2 or apparent antibody avidity for (QGPGAP)2 by sodium thiocyanate elution assay. The data demonstrate that a synthetic peptide can induce protective antibodies and that a specific antibody subclass is not required for protection. Work to determine whether antibody affinity or fine specificity can explain the hierarchy of protection among the MAbs is under way.

Amino Acid Sequence↗

T cell receptor-beta mRNA splicing: regulation of unusual splicing intermediates.

The expression of functional T cell receptor-beta (TCR-beta) transcripts requires the activation of programmed DNA rearrangement events. It is not clear whether other mechanisms dictate TCR-beta mRNA levels during thymic ontogeny. We examined the potential role of RNA splicing as a regulatory mechanism. As a model system, we used an immature T cell clone, SL12.4, that transcribes a fully rearranged TCR-beta gene but essentially lacks mature 1.3-kb TCR-beta transcripts in the cytoplasm. Abundant TCR-beta splicing intermediates accumulate in the nucleus of this cell clone. These splicing intermediates result from inefficient or inhibited excision of four of the five TCR-beta introns; the only intron that is efficiently spliced is the most 5' intron, IVSL. The focal point for the regulation appears to be IVS1C beta 1 and IVS2C beta 1, since unusual splicing intermediates that have cleaved the 5' splice site but not the 3' splice site of these two introns accumulate in vivo. The block in 3' splice site cleavage is of interest since sequence analysis reveals that these two introns possess canonical splice sites. A repressional mechanism involving a labile repressor protein may be responsible for the inhibition of RNA splicing since treatment of SL12.4 cells with the protein synthesis inhibitor cycloheximide reversibly induces a rapid and dramatic accumulation of fully spliced TCR-beta transcripts in the cytoplasm, concomitant with a decline in TCR-beta pre-mRNAs in the nucleus. This inducible system may be useful for future studies analyzing the underlying molecular mechanisms that regulate RNA splicing.

Animals↗

Cancer prevention and early detection: nursing students' knowledge, attitudes, personal practices, and teaching.

This study evaluated the impact of an educational workshop on nursing students' knowledge, attitudes, and personal practices regarding cancer prevention and early detection (CP&ED), as well as the effect that it had on their teaching of CP&ED recommendations. Four one-day workshops--which included lectures, small group discussions, and practice of early detection skills--were held in three cities in Minnesota. Students from baccalaureate, associate-degree, and practical nursing programs participated (N = 220). Preworkshop, postworkshop, and six-month follow-up surveys were used to evaluate the knowledge, attitudes, and self-practice of the participants, as well as their teaching of clients, family, friends, and peers. Data were analyzed with matched paired t-tests, chi-square, correlation, and analysis of variance. The postworkshop and six-month follow-up surveys showed improvement in the students' knowledge and attitudes; however, the only self-practice behaviors that changed within six months of the workshop were breast/testicular self-examinations. The results also showed that the students felt more confident and subsequently taught more clients, family, friends, and peers about the CP&ED recommendations. These findings indicate that educating students early in their careers may increase the number of people practicing CP&ED recommendations.

Adult↗