Search PubMed⌕ Search

Biomedical subjects

S Mitchell

Publications and source records attributed to S Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed1995

A prospective randomized trial of FK506-based immunosuppression after renal transplantation.

A group of 204 adult patients was entered into a prospective, randomized trial comparing FK506/prednisone with FK506/azathioprine/prednisone after renal transplantation between August 1, 1991 and October 11, 1992. The purpose of the study was to see if the addition of azathioprine would reduce the incidence of rejection and improve graft survival. The recipient population was unselected, with 61 (30%) patients undergoing retransplantation, 37 (18%) having a panel-reactive antibody greater than 40%, and 33 (16%) over 60 years of age. The mean recipient age was 43.8 +/- 13.7 years (range 17.6-78). The mean donor age was 34.0 +/- 20.1 years (range 0.3-75); 13% of the cadaveric kidneys were from pediatric donors less than 3 years of age and were transplanted en bloc. The mean cold ischemia time was 31.4 +/- 8.4 hr. Living donors were the source of 13% of the kidneys. The mean follow-up was 22 +/- 4 months (range 12-29). Overall one-year actual patient survival was 94%. Overall one-year actual graft survival was 87%. Patients starting on double therapy had a one-year actual patient survival of 96% and a one-year actual graft survival of 92%. Patients starting on triple therapy had a one-year actual patient survival of 91% (P = ns compared with double therapy), and a one-year actual graft survival of 82% (P < 0.02, compared with double therapy). Overall results with first cadaver transplants included a one-year actual patient survival of 94% and one-year actual graft survival of 88%, with no differences between double and triple therapy. The overall incidence of rejection was 48%, with 54% in the double therapy group and 41% in the triple therapy group (P < .07). The incidence of steroid-resistant rejection requiring antilymphocyte therapy (OKT3 or ATGAM) was 13%, and was not different between the double and triple therapy groups. The mean serum creatinine was 1.8 +/- 0.8 mg/dl. The mean BUN was 33 +/- 21 mg/dl, with no significant difference between the therapy groups. The mean serum cholesterol was 192 +/- 49 mg/dl. A total of 56% of the patients are off prednisone, and 35% of the patients are not taking any antihypertensive medications. Other complications included cytomegalovirus--14%; new-onset diabetes--16% (half of which was reversible); and posttransplant lymphoproliferative disorder--1%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Fish odour syndrome: verification of carrier detection test.

An oral trimethylamine challenge test has been used to confirm the heterozygous status of patients with 'fish-odour syndrome'. By measuring the percentage of total urinary trimethylamine-related material excreted as the N-oxide, no discrimination could be made between obligate heterozygotes (parents of 'fish-odour syndrome' patients) (n = 15; 96 +/- 2%, range 92-98%) and control individuals (parents of unaffected children) (n = 16; 96 +/- 2%, range 93-99%) on a normal diet. However, after ingesting a trimethylamine load (600 mg base) the obligate heterozygotes were clearly distinguishable (76 +/- 3%, range 71-79%) from controls (95 +/- 2%, range 91-99%) (t-test; p <0.001). One of a hundred apparently normal volunteers who were subsequently challenged with trimethylamine had a N-oxidation capacity which fell within the range found among the obligate heterozygotes.

Adult↗
PubMed1995

Community-based health care: a different approach to health outcomes.

Health sector organisations are undergoing a period of fundamental change. One set of changes is about increasing the capacity of the system to provide integrated client care. This paper discusses the practices that community health care workers have used to approach some basic issues of service integration. Although the discussion is about practices in community health, the issues are important for health care providers, managers and policy-makers throughout the health care system.

Australia↗
PubMed1995

Isolation and characterization of a candidate gene for progressive myoclonus epilepsy on 21q22.3.

The Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1) and autoimmune polyglandular disease type I (APECED) have been mapped to human chromosome 21q22.3 by genetic linkage analysis and/or linkage disequilibrium studies. In order to isolate the genes for these disorders, we have constructed BAC contigs in this region and a 14 week trisomy 21 fetal brain cDNA library. A direct cDNA selection technique, modified to permit the recovery 5' and 3' ends of cDNA, was applied to gene identification using the BAC contigs. We have isolated and characterized a novel gene defined by three overlapping but distinct cDNAs of 5, 3, and 3 kb in size all named EHOC-1 (Epilepsy, HOloprosencephaly Candidate-1). This gene maps less than 45 kb centromeric of D21S25, and spans at least 56 kb of genomic DNA. Northern analysis of the 5 kb cDNA revealed that 8, 7.5 and 5.3 kb transcripts are ubiquitously expressed in adult tissues. DNA sequence analysis of the 5 kb cDNA showed a complete coding sequence of 3570 bp that has multiple putative transmembrane domains and has partial homologies to transmembrane proteins including sodium channel proteins. This gene (EHOC-1) is a good candidate for APECED, and particularly for EPM1 because of the location, size, structure and homologies.

Amino Acid Sequence↗
PubMed1995

A high-fidelity physical map of human chromosome 21q in yeast artificial chromosomes.

Understanding of the human genome has been advanced significantly by the development of large DNA fragment libraries. To create a map of chromosome 21q that integrates the physical, cytogenetic, and linkage maps, we have characterized a subset of 127 chromosome 21 yeast artificial chromosome (YAC) clones for size, by pulsed field gel electrophoresis, for chimerism and cytogenetic location, by fluorescence in situ hybridization (FISH), and for sequence-tagged sites (STS) content, by PCR. It was found that 54% generated unique map locations on chromosome 21, and 45% detected sites on other chromosomes, of which 33% likely represented true chimerism. Using a simple algorithm, the data from nonchimeric clones have been combined to generate a size-corrected minimal tiling pathway including 58 chromosome 21q YACs that represent approximately 33 Mb and include 9 gaps. To confirm the resulting order and relationship to the cytogenetic map, the breakpoints from 23 cell lines partially aneuploid for chromosome 21 have been analyzed by quantitative Southern blot dosage analysis and FISH with a subset of the markers. As one way of investigating the relationship of the genetic to the physical map, the genetic map was superimposed on the physical map using a subset of well-defined markers common to both. The results suggest potential hot spots for recombination and/or gaps in the physical map. This integrated map will facilitate the search for the genes responsible for the Down syndrome phenotypes and provide a better understanding of genome organization and chromosome structure.

Aneuploidy↗
PubMed1995

Neuronal ceroid-lipofuscinosis in a cat.

Neuronal ceroid-lipofuscinosis was diagnosed in a young adult domestic short-haired cat euthanatized because of severe progressive neurologic disease. Clinical signs included blindness, seizures, and decreased mentation. An autofluorescent pigment, identified as ceroid-lipofuscin by electron microscopy and staining properties, was found within neurons of the central and peripheral nervous systems. A diffuse reactive astrocytosis accompanied by multifocal microgliosis was visible in all areas of the brain. Retinal atrophy with intraneuronal lipopigment accumulation was also identified. Contrary to the human neuronal ceroid-lipofuscinoses, pigment deposition appeared to be restricted to neural tissues.

Animals↗
PubMed1995

Reconstructions of populations of luteinizing hormone releasing hormone neurons in young and middle-aged rats reveal progressive increases in subgroups expressing Fos protein on proestrus and age-related deficits.

Fos expression has been used as a marker of activation of neuroendocrine cells including LHRH neurons. In this study, Fos protein was localized within LHRH neurons in young and middle-aged rats to trace the temporal and spatial pattern of LHRH neuronal activation associated with the preovulatory LH surge. Animals were killed during the late morning, afternoon, and evening of proestrus. Dual immunocytochemical protocols localized LHRH and LHRH/Fos neurons, and computer-assisted methods were used to reconstruct forebrain populations of single- and double-labeled LHRH neurons. Although a significant increase in the number of LHRH/Fos neurons was noted by evening in both age groups, a greater increase was observed in young (12% in morning, 28% in afternoon, and 62% by evening) compared with aging females (5% in morning, 10% in afternoon, and 40% by evening). Reconstructions of LHRH and LHRH/Fos neurons revealed time- and age-dependent differences in Fos expression within LHRH neurons. In young females, LHRH/Fos neurons were restricted to central regions of the population of LHRH neurons on the morning of proestrus. By evening, Fos expression was also observed in more peripheral and caudal LHRH neurons. In middle-aged females, Fos expression was restricted to ventral subgroups of LHRH neurons on the afternoon of proestrus. By evening, more LHRH neurons contained Fos protein, however, few were located in the dorsal aspect of the population. These data trace the progressive increase in activation of LHRH neurons during the preovulatory LH surge in young females and reveal deficits in this pattern of activation by middle age.

Aging↗
PubMed1995

Nurses helping nurses: development of internal specialists in long-term care.

1. Too often, expert assistance provided by psychiatrists and psychiatric nurse specialists to long-term care (LTC) providers of geriatric patients is short-lived and not effective in helping LTC staff deal with their patient's behavioral and psychological problems. 2. One of the main objectives of the study--and one that was found to have positive results--was to provide a mechanism by which LTC staff could develop their own expertise in the management of behaviorally difficult residents. 3. More collaborative efforts among nursing specialists, subspecialists, and generalists are needed to empower those who work in LTC to utilize the abilities and strengths inherent in their positions.

Humans↗
PubMed1995

Nurses helping nurses. Development of internal specialists in long-term care.

The prevalence of psychiatric disorders and behavioral disturbances among nursing home residents, combined with observed deficits in geriatric mental health/illness expertise among LTC staff, supports the need for creative approaches to improve the knowledge, understanding, and management of such problems among LTC providers. The train-the-trainer model described in this article proved to be a viable method to providing geriatric mental health consultation and training that targets both improved quality of life for residents and quality of work life for the staff in charge of residents' care. More collaborative efforts among nursing specialists, subspecialists, and generalists are needed to empower those who work in LTC to utilize strengths and abilities inherent to their positions. Nursing homes nurses, who are all too familiar with the problems and challenges of their patient population, may act not only as mental health trainers but also as resource persons, role models, liaisons with geropsychiatric specialists, and leaders in the application of geropsychiatric care principles to residents within their facility, thus promoting improved resident and staff care alike.

Aged↗
PubMed1994

Structure-immunogenicity relationship of melittin, its transposed analogues, and D-melittin.

Melittin, a 26-residue bee venom peptide, is known to induce murine Abs specific for its hydrophilic C-terminus of residues 20-26 and T cell responses specific for its hydrophobic mid-region of residue 11-19. Synthetic melittin analogues with transposed sequences of Ac(21-26) (1-20) and Ac(26-21) (1-20) are found to induce murine Abs specific for the transposed peptide segment and to induce T cell responses that are cross-reactive with melittin. Compared with melittin, the transposed melittin analogues are weaker immunogens and have lower hemolytic activities, lower helical contents, and a lower degree of association in micelles. A melittin analogue with a lactoside group at its C-terminus was found to induce lactoside-specific murine Abs. Present studies show that another analogue with a lactoside group at its N-terminus induces only Abs specific for the C-terminal region of melittin, and no lactoside-specific Abs are detected. These immunochemical observations suggest that the immunogenicity of melittin or its analogues is a consequence of its binding to cell membranes with subsequent oligomer formation in lipid bilayers. Apparently melittin or its analogues bind to cell membrane in an asymmetric manner with the exposed and the buried segments functioning as B and T cell epitopes, respectively. D-melittin is non-immunogenic in mice, although D-melittin has the same hemolytic activity as melittin. This finding may be correlated with the known resistance of D-melittin to proteolysis and hence to processing for Ag presentation to T lymphocytes.

Amino Acid Sequence↗
PubMed1994

Early death or retransplantation in adults after orthotopic liver transplantation. Can outcome be predicted?

Early, reliable outcome prediction after a liver transplant would help improve organ use by minimizing unnecessary retransplantations. At the same time, early intervention in those cases destined to fail may ameliorate the high morbidity and mortality associated with retransplantation. The purpose of this study was to analyze several parameters that have been identified in the past as being associated with patient and graft outcome, and to try to develop a model that would allow us to make predictions based on data available in the early postoperative period. A total of 148 patients were followed in a prospective, observational study. Graft failure was defined as patient death or retransplantation within 3 months of surgery. Preoperative variables studied included patient demographics, need for life support, presence of ascites, serum bilirubin, serum albumin, prothrombin time, serum creatinine, and the results of the cytotoxic crossmatch. During the first 5 postoperative days, standard measurements included serum transaminases, serum bilirubin, ketone body ratio, prothrombin time, factor V, and serum lactate. Oxygen consumption was measured shortly after surgery, once the patients had rewarmed to 36 degrees C. There were 131 successful transplants (88.5%) and 17 failures (11.5%). Most of the variables studied were found to be associated with outcome (by univariate analysis) at different points in the early postoperative period. However, receiver operating characteristic curve analysis showed that the predictive ability of even the best parameter was not adequate to make decisions on individual patients. Multivariate analysis, using stepwise logistic regression, yielded a model with an overall accuracy of 92.7%. Again, receiver operating characteristic curve analysis suggested that this model did not achieve the discriminating power needed for routine clinical use. We are still not able to accurately predict outcome in the early posttransplant period. We must be very careful when evaluating parameters, or scoring systems, that are said to accomplish this. It is especially important in this era of cost containment, with its renewed pressures to guide therapy based on our perceived understanding of a patient's future clinical course.

Bilirubin↗
PubMed1994

Geropsychiatric nursing consultation: a valuable resource in rural long-term care.

Psychiatric and geropsychiatric nurse specialists have the potential to positively influence the day-to-day care provided in rural nursing homes by acting as teachers, resource persons, facilitators, and role models to long-term care (LTC) personnel. The combined approach of training LTC nurses to train their own staff while supporting the application of learning with consultee-focused nursing consultation proved to be an effective and time-efficient method of improving the geropsychiatric nursing care provided in rural nursing homes.

Aged↗
PubMed1994

Prevalence and first-line treatment of diarrhoeal symptoms in the community.

By systematically sampling patient registers in two socio-economically contrasting Scottish urban general practices, 440 households were selected and contracted by a research health visitor who interviewed a household member in 425 of them (response rate = 97%). Information was obtained on the point and period prevalence of diarrhoeal symptoms in all household members (n = 1,335), and on the knowledge, attitudes and behaviour of the respondents. While the point prevalence was low (under 1% of the household members), around 12% were reported to have experienced symptoms in the three-month period prior to the interview, and these were associated with a small but far from negligible loss of time from school or work. There were no significant seasonal differences in prevalence rates, nor were there significant differences between the two practices. Knowledge about appropriate treatment was high, but there was some confusion about the administration of liquids (especially milk) other than water, and a high level of ignorance about the existence and purpose of oral rehydration solutions. These findings have implications for public education about the initial management of acute diarrhoeal symptoms.

Adolescent↗
PubMed1994

Duration of antibody response after meningococcal polysaccharide vaccination in US Air Force personnel.

The long-term kinetics of the immunologic response after vaccination of adults with Neisseria meningitidis polysaccharide vaccine is unknown. Total meningococcal anti-capsular antibody response (measured by ELISA) and serum bactericidal activity after routine vaccination with quadrivalent meningococcal vaccine were evaluated in US Air Force personnel. In a retrospective cross-sectional study, blood samples were obtained from approximately 40 personnel before vaccination, at 1 and 4-6 months, and at 2, 3, 4, 6, 8, and 10 years after vaccination. Total anti-group A and -group C capsular antibody levels and bactericidal activity peaked 1 month after vaccination and declined substantially by 2 years. At each interval, significantly higher levels of total antibody and bactericidal activity were detected than before vaccination. Anti-capsular antibodies and bactericidal activity persisted for up to 10 years after immunization. These and further studies on the serologic measure of protection against meningococcal disease are important for evaluation of candidate vaccines and development of recommendations for immunization.

Adult↗
PubMed1994

Predicting outcomes after liver transplantation. A connectionist approach.

OBJECTIVE: The authors sought to train an artificial neural network to predict early outcomes after orthotopic liver transplantation. SUMMARY BACKGROUND DATA: Reliable prediction of outcomes early after liver transplantation would help improve organ use and could have an impact on patient survival, but remains an elusive goal. Traditional multivariate models have failed to attain the sensitivity and specificity required for practical clinical use. Alternate approaches that can help us model clinical phenomena must be explored. One such approach is the use of artificial neural networks, or connectionist models. These are computation systems that process information in parallel, using large numbers of simple units, and excel in tasks involving pattern recognition. They are capable of adaptive learning and self-organization, and exhibit a high degree of fault tolerance. METHODS: Ten feed-forward, back-propagation neural networks were trained to predict graft outcomes, using data from 155 adult liver transplants. The data included information that was available by the second postoperative day. Ten separate training and testing data subsets were prepared, using random sampling, and the ability of the different networks to predict outcomes successfully was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Four of the networks showed perfect discrimination, with an area under the ROC curve (Az) of 1.0. Two other networks also had excellent performance, with an Az of 0.95. The sensitivity and specificity of the combined networks was 60% and 100%, respectively, when using an output neuron activation of 0.6 as the cutoff point to decide class membership. Lowering the cutoff point to 0.14 increased the sensitivity to 77%, and lowered the specificity to 96%. CONCLUSIONS: These results are encouraging, especially when compared to the performance of more traditional multivariate models on the same data set. The robustness of neural networks, when confronted with noisy data generated by nonlinear processes, and their freedom from a priori assumptions regarding the data, make them promising tools with which to develop predictive clinical models.

Adult↗
PubMed1994

Observation of a reversible, medication-induced change in pitch perception.

This paper reports a study of an absolute pitch possessor who, upon administration of the psychoactive drug Tegratol (carbamazepine), experienced a significant change in her pitch perception. The subject's performance both in producing, as well as in identifying, random-frequency tones was measured, covering the period of administration of the drug, as well as control periods before and after. The main effect of the drug was a downward shift of the perceived pitch as compared to the two control periods. The magnitude of the shift was observed to increase with increasing fundamental frequency of the stimulus; the average shift was about one semitone. Detailed results on the frequency dependence and time dependence of the pitch shifts are presented. This may be the first documented report of a significant, reversible change of pitch perception caused by a medication.

Acoustic Stimulation↗