Gender and development: a SAFE recipe.
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Economics↗
Biomedical subjects
S Mitchell
Publications and source records attributed to S Mitchell.
Respiratory health in a total very low birthweight cohort and their classroom controls.
AIMS: To compare the respiratory health and function at 8 to 9 years of age of a total population based cohort of 300 very low birthweight (VLBW) children with that of two classroom controls (n = 590) matched for age and sex. STUDY DESIGN: Cohort study with controls. SETTING: Schools throughout Scotland. RESULTS: The VLBW children were more likely than their peers to use an inhaler, to be absent from school, and to be admitted to hospital because of respiratory illness. They were significantly shorter than their classroom controls, but even after adjusting for differences in height, the VLBW children had reduced forced vital capacity (FVC); this was associated with a history of prolonged ventilation (> 28 days) and pneumothorax in the neonatal period. There were no significant differences between the groups in forced expiratory volume in one second (FEV1)/FVC but twice as many (7.9% v 3.7%) of the VLBW children had ratios < 70%, denoting obstructive airways disease. Poor expiratory function was associated with neonatal respiratory distress syndrome, prolonged ventilation, and the need for > 40% oxygen. Exercise induced airway narrowing was increased in VLBW children (odds ratio = 2.0; 95% confidence interval 1.2 to 3.4) and was very little changed by adjustment for inhaler use and exposure to cigarette smoke. CONCLUSIONS: As in other low birthweight cohorts, respiratory morbidity was increased. Unlike previous studies, FVC was more affected than expiratory function in this VLBW population. Our findings support the hypothesis that poorer lung function is associated with very low birth weight, but not with intrauterine growth retardation.
Asthma, Exercise-Induced↗
Diagnostic assays in cytomegalovirus retinitis.
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Cytomegalovirus Retinitis↗
Diagnostic difficulty arising from rectal recovery in ulcerative colitis.
AIMS: To ascertain whether the dogma that a normal rectal biopsy precludes a diagnosis of ulcerative colitis is correct. METHODS: Rectal biopsy specimens from a prospective group of 24 asymptomatic patients, with an established diagnosis of ulcerative colitis, were examined in a blinded study alongside 10 normal rectal biopsy specimens from an age and sex matched patient cohort without ulcerative colitis. Each biopsy specimen was assessed by three pathologists and ascribed to one of four categories: normal; borderline abnormality (one or more minor nonspecific abnormalities which, when combined, did not fulfil the minimal acceptable criteria for a diagnosis of ulcerative colitis); minimal features of chronic ulcerative colitis; and unequivocal ulcerative colitis. RESULTS: Two patients with ulcerative colitis had normal biopsy specimens; nine specimens were categorised as borderline abnormality, one as showing the minimal changes of chronic ulcerative colitis, and 12 as having the typical changes of chronic ulcerative colitis. Thus, 11 (46%) of the 24 patients had a rectal biopsy specimen that was devoid of the acceptable attributes on which a diagnosis is established, despite a confident previous diagnosis. Ten of these 11 cases had disease limited to the rectum. Review of all previous histological biopsy specimens (n = 164) and clinical data, including drug treatment, failed to identify any attributes that might be prognostic markers for future rectal mucosal healing. CONCLUSIONS: A normal rectal biopsy specimen, though uncommon, may occur in longstanding colitis. Moreover, in 46% of these asymptomatic but established cases the degree of healing may preclude a diagnosis of ulcerative colitis without comprehensive clinical and radiological details. Pathologists need to be aware of this minimal end of the spectrum of disease.
Adult↗
Tissue-specific gene expression from Mo-MLV retroviral vectors with hybrid LTRs containing the murine tyrosinase enhancer/promoter.
Transcriptional tissue specificity was engineered directly into Moloney Murine Leukaemia Virus (Mo-MLV)-derived retroviral vectors by replacing the viral enhancer in the 3' long terminal repeat (LTR) with two different lengths (2.5 kbp or 769 bp) of the murine tyrosinase promoter/enhancer. The hybrid tyrosinase-LTR was transferred to the proviral 5' LTR following viral packaging and infection of target cell lines. Hybrid tyrosinase-LTR-driven IL-2 production was barely above background levels in infected nonmelanoma cell lines containing intact provirus, whereas infected melanoma cell lines expressed high levels of IL-2 and the larger tyrosinase promoter/enhancer fragment directed higher levels of transgene expression. By replacing the viral enhancer with the tyrosine promoter/enhancer sequences, promoter interference effects which we have previously observed when the tyrosinase promoter was included as an internal promoter within a similar retroviral vector were effectively abolished. Our data show that the hybrid tyrosinase-LTR behaves as a tightly regulated melanocytic-specific regulatory element when embedded in an enhancer-deleted Mo-MLV LTR. The use of other heterologous cellular promoter/enhancer elements in similar vectors should allow the development of simpler, targeted retroviral vectors for the expression of genes in selected cell types and may eventually provide for the development of safer, more efficient vectors for use in human gene therapy.
3T3 Cells↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Recognising and treating thyroid-associated ophthalmopathy.
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Eye Diseases↗
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↗
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↗