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Biomedical subjects

M Barr

Publications and source records attributed to M Barr.

At least 19 recordsLinked to original sources
PubMed2006

Developments in clinical islet, liver thoracic, kidney and pancreas transplantation in the last 5 years.

Although organ transplantation has matured into a proven therapy for end-stage organ failure, the many notable developments of the past 5 years speak to the multitude of remaining challenges. Two new procedures, islet transplantation and adult-to-adult living donor liver transplantation, have emerged to enlarge our therapeutic armamentarium for Type 1 diabetes mellitus and end-stage liver disease, respectively. In cardiac transplantation, the acceptance of ventricular assist devices as destination therapy is a notable event in light of critical shortage of deceased donor organs. Both liver and lung allocation policies have made a dramatic paradigm shift away from waiting time toward the survival benefit of transplantation. Finally, primary threats to post-transplant longevity have gained an increasing share of the spotlight. Recognition of the impact of renal insufficiency for all nonrenal transplant recipients, of recurrent hepatitis C virus for liver recipients, and of accelerated vasculopathy for cardiac have identified novel end points for clinical trials.

Graft Survival↗
PubMed2003

Population dynamics and gene transfer in genetically modified bacteria in a model microcosm.

The horizontal transfer and effects on host fitness of a neutral gene cassette inserted into three different genomic loci of a plant-colonizing pseudomonad was assessed in a model ecosystem. The KX reporter cassette (kanamycin resistance, aph, and catechol 2, 3, dioxygenase, xylE) was introduced on the disarmed transposon mini-Tn5 into: (I) the chromosome of a spontaneous rifampicin resistant mutant Pseudomonas fluorescens SBW25R; (II) the chromosome of SBW25R in the presence of a naturally occurring lysogenic-phage (phage Phi101); and (III) a naturally occurring plasmid pQBR11 (330 kbp, tra+, Hgr) introduced into SBW25R. These bacteria were applied to Stellaria media (chickweed) plants as seed dressings [c. 5 x 104 colony-forming units (cfu)/seed] and the seedlings planted in 16 microcosm chambers containing model plant and animal communities. Gene transfer to pseudomonads in the phyllosphere and rhizosphere was found only in the plasmid treatment (III). Bacteria in the phage treatment (II) initially declined in density and free phage was detected, but populations partly recovered as the plants matured. Surprisingly, bacteria in the chromosome insertion treatment (I) consistently achieved higher population densities than the unmanipulated control and other treatments. Plasmids were acquired from indigenous bacterial populations in the control and chromosome insertion treatments. Plasmid acquisition, plasmid transfer from inocula and selection for plasmid carrying inocula coincided with plant maturation.

Bacteriophages↗
PubMed2001

Organ asymmetries as correlates of other anomalies.

Fetuses with deviations in the normal left versus right weight relationships of the paired viscera were examined for correlation with particular malformations, syndromes, or other common factors. Alterations of the normal pattern were observed among cases with cytogenetic anomalies, diaphragmatic hernia, renal duplication, dyshydramnios, and single umbilical artery. A reversal of the left versus right weight pattern was found in the adrenals of cases with hepatic situs inversus but not in those with heterotaxic cardiac lesions. Recipient twins in the twin-twin transfusion syndrome had reduced left lung weights, presumably because of inhibition of lung growth by the enlarged heart. The side of umbilical artery absence did not predict either the nature or complexity of associated malformations. However, it is suggestive that there is discordance between the side of the missing artery and unilateral renal abnormality and that there is preferential absence of the right or left artery, depending on the karyotype.

Adrenal Glands↗
PubMed2001

A foodborne outbreak of Vero cytotoxin-producing Escherichia coli O157:H-phage type 8 in hospital.

This paper describes the epidemiological and microbiological aspects of the largest outbreak of Vero cytotoxin-producing Escherichia coli O157 (VTEC O157) infection in a hospital setting in which the route of transmission was foodborne. The outbreak, which was caused by a relatively uncommon phage type of VTEC O157, occurred in four geriatric continuing care wards in May 1997. The total number of people found to be excreting the organism was 37, of whom 16 were inpatients and 11 were staff. Twelve people displayed enteric symptoms. In addition, all but two of 10 cases identified in the local community were thought to be associated with the outbreak. An epidemiological investigation amongst the hospital patients revealed a statistically significant association between VTEC O157 infection and attendance at a concert party on the continuing care wards on 17 May 1997 (relative risk = 3.22;P= 0.006). There was an even stronger relationship between consumption of home-baked cream-filled cakes brought to that party and evidence of infection (relative risk = 19.35;P= 0.00002). Further investigations in the local community, coupled with microbiological evidence, supported the epidemiological finding that homemade cream cakes brought into the hospital were the vehicle of infection for the outbreak. There was no secondary spread within the hospital. The outbreak serves as a reminder of the hazard posed by foodstuffs brought into a hospital from outside.

Aged↗
PubMed2001

Strategies for disseminating evidence-based practices to staff who treat people with serious mental illness.

Evidence-based practices have not been widely implemented in real-world treatment settings for several reasons, including existing state laws, administrative policies, funding priorities, advocates' concerns, and program staffing. Dissemination strategies focus largely on program staffing and the question of why treatment teams that are responsible for assisting people with serious mental illness fail to use evidence-based practices. In a review of the research literature, two barriers to staff dissemination emerge: individual service providers lack the necessary knowledge and skills to assimilate these practices, and certain organizational dynamics undermine the treatment teams' ability to implement and maintain innovative approaches. Three sets of strategies are useful for overcoming these barriers and fostering dissemination: packaging evidence-based practices so that specific interventions are more accessible and user-friendly to service providers; educating providers about relevant knowledge and skills; and addressing the organizational dynamics of the team to facilitate the implementation of innovations. Research on dissemination is relatively new and is less well developed than the clinical and services research enterprise that has led to evidence-based practices. Implications for future studies are discussed.

Chronic Disease↗
PubMed2001

The effect of pleural adhesions on pediatric cystic fibrosis patients undergoing lung transplantation.

The degree of pleural scarring complicating cystic fibrosis (CF) lung disease is thought to impact on the outcome of adult lung transplantation. This has not been previously studied in the pediatric population. We studied all patients undergoing lung transplantation at Children's Hospital Los Angeles from 1993 through 2000. Operative times, grade of pleural scarring, blood product transfusion requirements, and perioperative mortality were compared for patients with cystic fibrosis (35) versus those without this diagnosis (11). Patients with CF were slightly older (14.7+/-3.8 vs 10.6+/-5.6 years; P = 0.01) but had similar weights (34.8+/-8.7 vs 34.4+/-12.3 kg). The degree of pleural scarring was greater in the CF group but was only severe in four patients. Scarring did not impact on operative times (237+/-46 vs 219+/-39 minutes; P = 0.22) or cardiopulmonary bypass times (127+/-40 vs 133+/-49 minutes). Total perioperative blood requirements for the two groups were similar (35.6+/-14.9 vs 42.8+/-76.7 cm3/kg; P = 0.82). Pleural scarring in the pediatric CF patients undergoing lung transplantation is only severe in a minority of patients. It does not increase duration of operation nor blood transfusion requirements. CT scanning is consequently unnecessary in the preoperative workup of CF patients being evaluated for transplantation. CF patients undergoing transplantation have perioperative outcomes similar to those of noncystic patients.

Adolescent↗
PubMed2000

Angiotensin II has multiple profibrotic effects in human cardiac fibroblasts.

BACKGROUND: Angiotensin II (Ang II) is implicated in cardiac remodeling and is increasingly recognized for its profibrotic activity. METHODS AND RESULTS: Because little is known about the direct cellular effects of Ang II on human cardiac fibroblasts, we isolated fibroblasts from ventricles of explanted human hearts and added Ang II (100 nmol/L) to determine its role in growth, extracellular matrix accumulation, and adhesion. To assess which Ang II receptor is involved, Ang II was added in the presence of irbesartan (10 micromol/L), a specific AT(1) receptor antagonist; PD 123319 (10 micromol/L), a specific AT(2) receptor antagonist, or divalinil (100 nmol/L), an AT(4) receptor inhibitor. In human ventricles (n=13), message levels of atrial natriuretic peptide and AT(1) receptor were inversely correlated, which suggests a decrease in AT(1) receptor expression with progressive heart failure. Northern analysis and fluorescence-activated cell sorting demonstrated AT(1) receptor in cultured human cardiac fibroblasts. Ang II increased mitogen-activated protein kinase activity and in DNA synthesis (5-fold, P<0.01) stimulated a 2-fold increase in transforming growth factor-beta(1) (P<0.05) mRNA levels at 2 hours and a 2-fold increase in laminin (P<0.05) and fibronectin (P<0.05) mRNA levels at 24 hours. Ang II also enhanced plasminogen activator inhibitor-1 expression, which inhibits metalloproteinases that degrade the extracellular matrix. All of these effects were inhibited by irbesartan but not PD 123319 or divalinil. In addition, Ang II increased cardiac fibroblast attachment to collagens I and III, which was associated with an increase in focal adhesion kinase activity. CONCLUSIONS: Activation of the AT(1) receptor in human heart promotes fibrosis. Ang II plays a novel role in stimulation of plasminogen activator inhibitor-1 expression and adhesion of cardiac fibroblasts to collagen.

Adolescent↗
PubMed2000

Fronto-otopalatodigital osteodysplasia: clinical evidence for a single entity encompassing Melnick-Needles syndrome, otopalatodigital syndrome types 1 and 2, and frontometaphyseal dysplasia.

Otopalatodigital syndrome type 2 is an X-linked disorder with minimal expression in carrier females and comprises typical facial anomalies and a generalized bone dysplasia with osteodysplastic changes, brachydactyly, and impaired survival. Recently several other severe malformations were reported in the condition. Melnick-Needles syndrome is an X-linked dominant disorder. Affected males are usually sporadic cases. The exceptional males born to symptomatic women present with a lethal disorder comprising generalized osteodysplasia, deficiency of the first ray, and facial anomalies strikingly similar to those of otopalatodigital syndrome type 2. We report here on three boys with classical, severe, and lethal otopalatodigital type 2 syndrome, and three boys with severe (lethal) Melnick-Needles syndrome, born to affected mothers. We suggest that otopalatodigital type 1 and 2, Melnick-Needles syndrome and frontometaphyseal dysplasia, sharing many clinical manifestations and a similar mode of inheritance, are variants of the same condition: fronto-otopalatodigital osteodysplasia. The relationships to similar syndromes (i.e., Saint-Martin-Gardner-Morrisson syndrome, serpentine fibula syndrome, atelosteogenesis type 3, boomerang dysplasia, and Yunis-Varon syndrome) are discussed.

Abnormalities, Multiple↗
PubMed2000

A history of the Teratology Society.

BACKGROUND: The 39-year history of the Teratology Society is reviewed. An abbreviated history is outlined in table form, along with listings of the Warkany Lectures, the postgraduate courses, and officers of the Society. METHODS: A year-by-year description of the events, including the scientific and social content of the annual meetings and changes in the business of the Society, is given, in many cases using comments from the past presidents. The valuable and unique diversity of the members is discussed and illustrated, presenting the disciplines and main research area of the presidents. The number of submitted abstracts and the various categories are tabulated, averaging the number and type over four periods. Within the past 10 years, a significant increase in the number of abstracts dealing with epidemiology and developmental biology is evident. The Society's development is compared with that of a human, and the question is asked: Have we reached the maturational stage of old age or senescence, or is the Society still maturing gracefully? This question needs further discussion by all the members. RESULTS: During the past 40 years, we have developed the scientific basis to prevent birth defects caused by rubella, alcoholism, and folate deficiency, as well as many other prenatal exposures. CONCLUSIONS: We must now engage in the political battles to obtain the resources needed to conduct further research and to implement the prevention programs, as well as to provide care and rehabilitation for persons with birth defects.

History, 20th Century↗
PubMed2000

Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.

McKusick-Kaufman syndrome (MKKS, MIM 236700) is a human developmental anomaly syndrome comprising hydrometrocolpos (HMC), postaxial polydactyly (PAP) and congenital heart disease (CHD). MKKS has been mapped in the Old Order Amish population to 20p12, between D20S162 and D20S894 (ref. 3). Here we describe the identification of a gene mutated in MKKS. We analysed the approximately 450-kb candidate region by sample sequencing, which revealed the presence of several known genes and EST clusters. We evaluated candidate transcripts by northern-blot analysis of adult and fetal tissues. We selected one transcript with widespread expression, MKKS, for analysis in a patient from the Amish pedigree and a sporadic, non-Amish case. The Old Order Amish patient was found to be homozygous for an allele that had two missense substitutions and the non-Amish patient was a compound heterozygote for a frameshift mutation predicting premature protein truncation and a distinct missense mutation. The MKKS predicted protein shows amino acid similarity to the chaperonin family of proteins, suggesting a role for protein processing in limb, cardiac and reproductive system development. We believe that this is the first description of a human disorder caused by mutations affecting a putative chaperonin molecule.

Abnormalities, Multiple↗
PubMed2000

Review article: non-steroidal anti-inflammatory drugs and Helicobacter pylori.

Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori are well-recognized causes of gastroduodenal mucosal damage. This damage is mediated through the effects of both agents on acid secretion, neutrophil activity and function, and prosta- glandin metabolism. Clinical trials on the interrelation- ship between H. pylori, NSAIDs and gastroduodenal mucosal injury have yielded conflicting results. No consensus has been reached on what recommenda- tions should be implemented with regard to H. pylori eradication in patients on long-term NSAID therapy. At present, the presence of H. pylori is identified at endoscopy and eradication is carried out in symptomatic patients. Asymptomatic patients remain a dilemma that requires further investigation. Clinical practice will continue to be tailored to a patient's individual requirements. Therefore, in patients at risk of gastrointestinal haemorrhage, and on NSAID therapy, acid suppression therapy should be prescribed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Patient satisfaction with a new nurse practitioner service.

In the UK the role of the Nurse Practitioner (NP) has been slower to develop than in the USA (Tye 1997). However, since its inception, studies of the role have found positive results in areas of patient satisfaction (Touche Ross 1994). James and Pyrgos (1989) reported 94% of patients suitable to seen by a NP would use a NP if introduced. A study by Freij et al. (1996) concluded that emergency NPs were as competent at interpreting X-rays as casualty officers. Despite such evidence, Meek et al. (1995) noted opposition to this new advanced practice from other disciplines who wished to maintain the 'status quo'. In light of these findings, a study was undertaken to examine the new NP Service at Antrim Hospital, Northern Ireland. A patient satisfaction survey, a retrospective X-ray audit and a subjective assessment by other disciplines, were carried out in order to evaluate the service.

Clinical Competence↗
PubMed2000

Workshop to identify critical windows of exposure for children's health: cardiovascular and endocrine work group summary.

The work group on cardiovascular and endocrine effects was asked to review the current state of knowledge about children's windows of vulnerability to developmental toxicants and to recommend how that information may be used to improve risk assessment and public health. We considered differences between structural defects, where periods of vulnerability are rather well defined, and functional defects, where periods of vulnerability are quite elusive.

Cardiovascular System↗
PubMed1999

Holoprosencephaly survival and performance.

Parents of children with holoprosencephaly often have been told that their children will die within days or weeks. When this does not happen, they are distrustful of the information they have received and want to know what they can really expect and how they can cope with the many problems these children have. We have recorded our experiences and gleanings from the literature with regard to survival and performance of these children. Survival data were obtained from 62 cases of alobar holoprosencephaly known to us or to our colleagues. Performance data were obtained on 35 survivors, by direct examination and/or detailed parent questionnaires and interviews.

Brain↗
PubMed1999

Aphallia as part of urorectal septum malformation sequence in an infant of a diabetic mother.

A male patient with aphallia, anal stenosis, tetralogy of Fallot, multiple vertebral anomalies including sacral agenesis and central nervous system (CNS) malformations was born after a pregnancy complicated by poorly controlled maternal diabetes. Aphallia is an extremely rare abnormality and can be part of the urorectal septum malformation sequence (URSMS). While aphallia has not been reported in infants of diabetic mothers, urogenital malformations are known to occur with increased frequency. Two female products of pregnancies complicated by diabetes presented with multiple malformations including anal atresia and recto-vaginal fistula consistent with the diagnosis of URSMS. The three patients share CNS, cardiac, and vertebral anomalies, abnormalities secondary to abnormal blastogenesis and characteristic of diabetic embryopathy. URSMS is also caused by abnormal blastogenesis. Therefore, this particular malformation should be viewed in the context of the multiple blastogenetic abnormalities in the cases reported here. The overlap of findings of URSMS in our cases with other abnormalities of blastogenesis, such as VATER association or sacral agenesis is not surprising, as these associations are known to lack clear diagnostic boundaries.

Central Nervous System↗
PubMed1998

Correlates of prenatal visceromegaly.

Aside from recognized overgrowth syndromes, instances of visceromegaly are not uncommon at perinatal autopsy. The database of the University of Michigan Teratology Unit was screened for individual viscera exceeding the 90th centile for body and brain weight standards. The data were stratified for several maternal (hypertension, diabetes, obesity), gestational (chorioamnionitis, oligohydramnios, amniorrhaea, polyhydramnios), and fetal (body wall defect, cardiac malformation, renal malformation, diaphragmatic hernia, nonimmune hydrops, twin transfusion syndrome) characteristics and tested for statistically significant excessive numbers of heavy organs. The most striking associations were heavy adrenal glands and liver with chorioamnionitis, heavy heart with polyhydramnios and in the twin transfusion syndrome, and heavy heart and liver with nonimmune hydrops. Excessive brain weight for body weight had a number of correlations, each most likely reflecting growth restriction with sparing of brain growth.

Autopsy↗