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Biomedical subjects

V Anderson

Publications and source records attributed to V Anderson.

At least 55 records · Page 3Linked to original sources

Outcome of twin pregnancy in a renal transplant recipient treated with tacrolimus.

Our report describes the outcome of a twin pregnancy in a woman who was maintained on tacrolimus after a living related renal transplant. Both babies born at 32 weeks of gestation developed severe respiratory distress requiring ventilator assistance and went on to develop congestive heart failure. Echocardiograms on both babies showed dilated heart chambers. Twin A succumbed to complications, but twin B, who was treated more aggressively with vasopressors, recovered. Autopsy findings on twin A revealed a thrombotic cardiomyopathy with degeneration of cardiac muscle. We believe that the unusual outcome in this set of twins may have been a result of cardiomyopathy secondary to tacrolimus used by the mother during her pregnancy.

Azathioprine↗

Cyclin dependent kinase-5 (CDK-5) phosphorylates neurofilament heavy (NF-H) chain to generate epitopes for antibodies that label neurofilament accumulations in amyotrophic lateral sclerosis (ALS) and is present in affected motor neurones in ALS.

1. Accumulations of phosphorylated neurofilaments are seen in affected motor neurones in amyotrophic lateral sclerosis (ALS). 2. The authors demonstrate that cyclin dependent kinase-5 (cdk-5) will induce cellular phosphorylation of neurofilament heavy chain side-arms to generate epitopes for several antibodies that label these neurofilament accumulations. 3. By creating recombinant neurofilament fragments of NF-H side-arm domains, the authors also map the epitopes for several of these antibodies. 4. Finally, the authors demonstrate that cdk-5 is also present in affected motor neurones in ALS. These studies implicate cdk-5 in the pathogenesis of ALS.

Aged↗

A prospective analysis of the recovery of attention following pediatric head injury.

Little is known about specific attentional sequelae following a closed head injury, their pattern of recovery or their interaction with ongoing development. The present study examined attentional abilities in a group of children who had sustained a mild, moderate, or severe head injury. Results showed that the severe head injury group exhibited greater deficits on a number of attentional measures at acute and 6 months postinjury phases, in comparison to children in the mild and moderate head injury groups. Specifically, deficits were most evident on timed tasks where speed of processing was an integral component. Difficulties persisted to at least 6 months postinjury and so may lead to cumulative deficits over time.

Attention↗

Endoscopic features of intestinal smooth muscle tumor in a child with AIDS.

Intestinal leiomyosarcomas are exceedingly rare in immunologically intact children, except during infancy. While leiomyosarcomas account for less than 2% of all soft tissue tumors in childhood, they are the second most frequent malignancy in children with the acquired immunodeficiency syndrome (AIDS). In this cohort they are often located in unusual sites for primary soft tissue tumors. This report describes a young girl with advanced AIDS, referred for evaluation of abdominal pain, hematochezia, and wasting syndrome. Colonoscopy revealed two 1- to 2-cm submucosal nodules with central umbilication. Repeat colonoscopy 18 months later revealed no changes in these lesions. Biopsy revealed a submucosal spindle-cell lesion, with necrosis and cellular atypia. Initially it was characterized as a partially excised low-grade leiomyosarcoma. However, the final consensus diagnosis was smooth muscle tumor of uncertain malignant potential. Because of her advanced AIDS, there was no attempt at surgical resection or chemotherapy. Thirty-six months after initial referral, she remains alive without radiographic or clinical evidence of local extension or metastases. Additional data are required to determine the long-term outcome of these indolent submucosal tumors in the digestive tracts of children with AIDS.

Acquired Immunodeficiency Syndrome↗

Impairments of attention following childhood traumatic brain injury.

Attentional deficits are commonly reported following traumatic brain injury (TBI) in adults, although the occurrence of such problems is less well documented in young children. This study aimed to investigate residual attentional abilities associated with TBI during childhood, by examining a number of aspects of attention including sustained, focussed, and divided attention, attentional shift, and response inhibition. Eighteen children with a history of TBI, aged between 8 and 14 years and 18 non-injured matched controls participated in the study. Results show that attentional skills may be differentially impaired after TBI, with children who have sustained moderate-to-severe TBI exhibiting significant deficits on the following attentional domains: sustain, focus, and response inhibition. These findings support the view that attentional impairments following pediatric TBI, while not global, may be more generalized than those reported for adult samples, perhaps reflecting the relative immaturity of attentional skills at the time of injury.

Adolescent↗

Attentional skills in the acute phase following pediatric traumatic brain injury.

Only a limited number of studies have investigated attention following pediatric head-injury. The present study examined sustained attention and processing speed in a group of children who had sustained a mild (n = 27), moderate (n = 33) or severe (n = 16) traumatic brain injury (TBI). No significant differences were evident between the TBI groups on reaction time measures. Results did show that the severe TBI group exhibited greater deficits in the area of sustained attention, in comparison to children with mild and moderate injuries, in the acute stage following traumatic brain injury. This difficulty may impact on the future development of skills dependent on intact attentional capacity.

Attention↗

Kinetic analysis of an inhibitor-resistant variant of the OHIO-1 beta-lactamase, an SHV-family class A enzyme.

The Met69-->Ile mutant of the OHIO-1 beta-lactamase, an SHV-family enzyme, is resistant to inactivation by beta-lactamase inhibitors. Analysis of purified Met69-->Ile enzyme reveals that its isoelectric point (pI 7.0) and CD spectrum are identical with those of the OHIO-1 enzyme. Levels of beta-lactamase expression in Escherichia coli as determined by immunoblotting are similar for OHIO-1 and Met69-->Ile beta-lactamase. The kinetic constants of the Met69-->Ile enzyme compared with OHIO-1 are smaller for benzylpenicillin (Km = 6 microM compared with 17 microM; kcat = 234 s-1 compared with 345 s-1 respectively) and carbenicillin (Km = 3 microM compared with 17 microM; kcat = 131 s-1 compared with 320 s-1 respectively). For the cephalosporins cephaloridine and 7-(thienyl- 2-acetamido)-3-[2-(4-N,N- dimethylaminophenylazo)pyridinium-methyl]-3-cephem-4-carboxylic acid (PADAC), a similar pattern is also seen (Km=38 microM compared with 96 microM and 6 microM compared with 75 microM respectively; kcat = 235 s-1 compared with 1023 s-1 and 9 s-1 compared with 50 s-1 respectively). Consistent with minimum inhibitory concentrations that show resistance to beta-lactam beta-lactamase inhibitors, the apparent Ki values, turnover numbers and partition ratios (kcat/kinact) for the mechanism-based inactivators clavulanate, sulbactam and tazobactam are increased. The inactivation rate constants (kinact) are decreased. The difference in activation energy, a measurement of altered affinity for the wild-type and mutant enzymes leading to acylation of the active site, reveals small energy differences of less than 8.4 kJ/mol. In total, these results suggest that the Met-->Ile substitution at position 69 in the OHIO-1 beta-lactamase alters the active site, primarily affecting the interactions with beta-lactamase inhibitors.

Anti-Bacterial Agents↗

Cyclin-dependent kinase-5 is associated with lipofuscin in motor neurones in amyotrophic lateral sclerosis.

We have studied the distribution of cyclin dependent kinase-5 (cdk-5) within spinal cord in sporadic and two superoxide dismutase type 1 (SOD1) familial cases of amyotrophic lateral sclerosis (ALS). Although most neurofilament accumulations in ALS motor neurones did not appear to contain high levels of cdk-5, intense cdk-5 immunoreactivity was observed in perikarya of degenerating neurones in many ALS cases. Here, cdk-5 co-localised with lipofuscin. Co-localisation of cdk-5 with lipofuscin was also observed in some aged non-affected controls although this labelling was less intense than the ALS cases. The biogenesis of lipofuscin is believed to be linked to oxidative stress and oxidative stress and free radical damage have been suggested to be part of the pathogenic process of ALS, possibly involving apoptotic mechanisms. cdk-5 has recently been associated with apoptosis. These observations suggest a role for cdk-5 in the pathogenesis of ALS.

Adult↗

Psychosocial aspects of adolescent cancer survival.

OBJECTIVE: The purpose of this research was to examine the psychosocial status of adolescent cancer survivors and compare them with healthy peers. It has been suggested in previous research that the majority of survivors display equivalent levels of psychosocial functioning post-treatment as compared with healthy controls. However, despite successful treatment, survivors may have to adjust to living with a chronic illness and its associated late effects interspersed across the lifespan (e.g. infertility, cognitive deficits, heart complications). Whilst young people appear to have similar levels of psychosocial functioning, avoidance strategies such as denial may result in previous research findings being confounded and in underestimating the true psychosocial status of survivors. It is important to understand the psychosocial status of survivors in order to optimise their quality of life. METHODOLOGY: Coping mechanisms, anxiety levels and self-concepts of 32 adolescent cancer survivors, predominantly Acute Lymphoblastic Leukaemia (ALL) were compared with 34 healthy adolescents (age range 12-17 years), via a mailout. RESULTS: Survivors' self-reports suggest no overt psychological dysfunctioning. Whilst the two groups shared similar coping strategies, survivors were found to be less anxious than peers, with a tendency to employ avoidance strategies to deal with problems faced in adolescence. Age, gender and specific illness variables, such as age at diagnosis and time since treatment, were strong predictors of psychological outcome. CONCLUSIONS: Results can be interpreted as suggesting that whilst cancer survivors have a similar psychosocial profile to healthy peers, they are more likely to utilise avoidance strategies to manage problems.

Adaptation, Psychological↗

Attentional skills following traumatic brain injury in childhood: a componential analysis.

Recent research has documented residual deficits in attention following traumatic brain injury in childhood. The present study aimed to investigate whether such deficits are global, or affect specific components of attention differentially. Four attentional domains were examined using a newly developed test of attention, the Test of Everyday Attention for Children: sustained attention, focussed attention, divided attention, and response inhibition. Eighteen children with a history of traumatic brain injury, aged between 8 and 14 years, and 18 non-injured matched controls participated in the study. Results indicated that attentional skills may be differentially impaired after TBI, with children who have sustained moderate-to-severe TBI exhibiting significant deficits for sustained and divided attention, and response inhibition, but relatively intact focussed attention.

Adolescent↗

Infrapopliteal transcatheter interventions for limb salvage in diabetic patients: importance of aggressive interventional approach and role of transcutaneous oximetry.

OBJECTIVES: This study sought to determine whether infrapopliteal transcatheter interventions can salvage ischemic limbs in diabetic patients referred for below the knee amputation at our institution. BACKGROUND: The value of transcatheter interventions in diabetic crural arteries is controversial. Tissue oxygen partial pressure (TCO2) levels < 40 mm Hg predict poor wound healing. METHODS: Percutaneous interventions were performed in 29 consecutive diabetic patients in need of limb salvage. Technical success was defined as < 20% residual vessel stenosis. Clinical success was defined as the avoidance of amputation and achievement of wound healing. At hospital discharge, patients were treated with Coumadin and aspirin. Ankle-brachial index (ABI) and TCO2 measurements were obtained before and after the intervention. RESULTS: After 12-month follow-up, six patients had presistent wounds, whereas 23 experienced wound healing. Forty of the 50 infrapopliteal arteries successfully dilated were occluded, with a mean (+/-SD) lesion length of 18.0 +/- 3.5 cm. After the procedure, TCO2 improved from 27.82 +/- 9.97 mm Hg (95% confidence interval [CI] 23.95 to 31.69) to 54.5 +/- 14.73 mm Hg (95% CI 48.79 to 60.21, p < 0.0001), whereas the ABI did not (p > 0.2). TCO2 predicted procedural and clinical success (p < 0.0182). CONCLUSIONS: Infrapopliteal transcatheter interventions in diabetic patients may salvage the majority of limbs doomed to amputation. Although TCO2 measurements are valuable in predicting wound healing and success after interventions, ABI measurements are not.

Angiography↗

IgE-bearing cells and epsilon-specific mRNA in lymphoid organs of two children with AIDS.

To characterize the cellular basis of IgE responses in HIV-positive (HIV+) children, we obtained central (bone marrow [BM], thymus) and peripheral (Peyer's patches [PP], mesenteric [MLN], and other lymph nodes [OLN], spleen), lymphoid organs from two children with AIDS (females, 2 and 8 years old), and from a non-HIV-infected trauma victim (female, 5 years old) at autopsy. PP were obtained from one of the HIV+ children (2 yr old) and from the non-infected child, but no PP were detected in small intestine of the 8-yr-old HIV+ child. Numbers of lymphocytes bearing surface IgE, CD19, CD3, CD4, and CD8 in lymphoid organs were determined (flow cytometry) and evaluated for expression of epsilon-specific (E) mRNA (RT-PCR). Thymus and MLN of the HIV+ child without PP contained high numbers of IgE+ (34% and 41%, respectively) and CD19+ (32% and 28%, respectively) cells; IgE+ cells were not found in any other organ. In contrast, in the HIV+ child with PP, IgE+ cells were detected in all organs, except BM. The thymus of this child contained fewer CD19+ cells (7%). However, in both HIV+ children, all lymphoid organs, including thymus, contained E mRNA. Because numbers of IgE+ cells often far exceeded numbers of CD19+ B cells, and because CD8+ T cells predominated in all organs, some of the IgE+ cells were probably CD8+ T cells with cytophilic IgE and may include IgE-specific regulatory and/or memory T cells. IgE responses were not detected in the healthy trauma victim nor were B cells found in thymus. The data suggest that during HIV infection, IgE+ B cells may be found in thymus and that synthesis of IgE may occur in all lymphoid organs except BM.

Acquired Immunodeficiency Syndrome↗

Childhood bacterial meningitis: impact of age at illness and acute medical complications on long term outcome.

This study compared postmeningitic children (N = 130) with grade and sex matched controls (N = 130) selected from target children's schools on measures of intellectual, linguistic, learning, and reading skills. Results showed that children with a history of meningitis are at greater risk for impairment in these areas, with experience of the disease prior to 12 months of age being an important risk factor. Within the postmeningitic sample presence of medical complications was associated with poorer verbal abilities. Finally, a significant relationship was identified between depressed language skills and later educational difficulty, with these findings interpreted with respect to both developmental and neuropsychological principles.

Adolescent↗

Male and female adolescents' perceived interpersonal communication skills according to history of sexual coercion.

This report summarizes the experience of 61 female adolescents recruited through a private adolescent family planning clinic, and 183 9th through 12th-grade adolescents recruited from a private suburban high school regarding their experiences with dating relationships, sexual communication skills, and psychological status. The samples were predominantly white and middle to upper income. Perceptions of interpersonal communication skills were analyzed according to gender, clinic versus school, and history of sexual coercion. The adolescents were generally confident that they could assert their own preferences and stand up to other regarding sexual issues with the exception of the small group of high school males reporting having had experienced sexual coercion. This group (N = 20) expressed difficulty in talking to their partners about safer sex, getting their partner(s) to listen to them, or turning down alcohol or drugs prior to having sex. These boys were also more likely to report missing classes or having other kinds of trouble with school, to be concerned about use of alcohol and drugs, and about feeling unpopular. None of the female groups had this profile of communication and emotional problems. Implications for preventive education programming on interpersonal skills and sexuality are considered.

Adaptation, Psychological↗

Predictors and indicators of academic outcome in children 2 years following traumatic brain injury.

Within the context of a longitudinal study investigating outcome for children following traumatic brain injury, this paper reports on the utility of neuropsychological testing in predicting academic outcome in children 2 years following traumatic brain injury (TBI). Twenty-nine school-age children who were admitted to hospital after TBI were assessed with a battery of neuropsychological and academic measures at 3 and 24 months postinjury. The neuropsychological battery included measures of memory, learning, and speed of information processing. Academic outcome was assessed in terms of post-TBI change in school placement. According to logistic regression analysis, change in placement from regular to special education at 2 years post-TBI was predicted by injury severity and by neuropsychological performance at 3 months post-TBI. Findings suggest that neuropsychological testing is useful in identifying children with special educational needs subsequent to TBI.

Adolescent↗

Neuropsychological, olfactory, and hygiene deficits in men with negative symptom schizophrenia.

Associations between symptom subtypes, life skills, olfactory identification, and neuropsychological ability were investigated in patients with schizophrenia and related to observations of poor personal hygiene and implied functional compromise of orbitofrontal integrity. Twenty-seven men with chronic schizophrenia were assessed using the Positive and Negative Syndrome Scale for Schizophrenia and the Life Skills Profile. Performance on the University of Pennsylvania Smell Identification Test (UPSIT), the Modified Wisconsin Card Sorting Test (MWCST), delayed response/alternation, and memory tasks derived from the Wechsler Memory Scale-Revised (WMS-R) was also compared to that of an age-, sex-, and IQ-matched control group. Patient UPSIT, MWCST, and WMS-R performance was significantly impaired in comparison to controls. Poor UPSIT performance and poor self-care were significantly associated with negative symptoms. Also, UPSIT ability was associated with performance on the MWCST in both patients and controls, whereas an association with performance on the WMS-R was only found in normal subjects rather than in the patients with schizophrenia. The importance of these findings to postulated mechanisms involving prefrontal rather than mediotemporal lobe (MTL) function in schizophrenia are discussed, as is the relevance of the use of smell identification ability to subtype identification and rehabilitative strategies.

Activities of Daily Living↗

Identification of a C-reactive protein binding site in two hepatic carboxylesterases capable of retaining C-reactive protein within the endoplasmic reticulum.

C-reactive protein (CRP) is normally synthesized by hepatocytes at relatively low rates and is retained within the endoplasmic reticulum (ER) via interaction with two carboxylesterases (termed gp60a and gp60b), which themselves are restricted to the ER by their COOH-terminal retention signals (HIEL and HTEL). During the acute phase response, an increase in CRP synthesis is accompanied by a decrease in its ER retention as a result of a decrease in the CRP binding affinity of gp60b. Our previous data indicated that the esterase active site, the CRP binding site, and the ER retention signal are functionally distinct. In the present studies, we have identified CRP-binding peptides produced by proteolytic cleavage of gp60a. The sequence shared by two CRP-binding peptides indicated that the CRP binding site of gp60a is contained within residues 477-499. These results were confirmed by expression of cDNAs coding for gp60a and b as bacterial fusion proteins. Fusion proteins containing the complete esterase COOH terminus bound CRP, whereas those truncated at residue 477 (or the homologous site in gp60b) did not. Based on the known crystal structures of three homologous hydrolases, the putative CRP-binding site of the gp60s is located on the surface and is physically distant from the esterase active site and the COOH-terminal ER retention signal.

Amino Acid Sequence↗

Localization and distribution of vasoactive neuropeptides in the human placenta.

Neuropeptides play an important role in the regional regulation of blood flow and hormone secretion. Few studies report the presence of peptides in the human placenta. Our experiment evaluates neuropeptides in the human placenta using immunocytochemical techniques. Representative tissue sections from full-term placentae were fixed immediately after delivery and processed into paraffin sections or frozen. They were treated with multiple immunofluorescence, streptavidin-biotin-peroxidase complex and immunogold-silver staining techniques in combination with well-established monoclonal and polyclonal antibodies, using appropriate absorption controls to ensure the validity of the staining. Vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), neuropeptide tyrosine (NPY), galanin, somatostatin, met-enkephaline, helodermin and substance P-like immunoreactivities were demonstrated within decidual cells. Endothelin-1 was found in both trophoblasts and endothelial cells. Peptide immunoreactivities in the human placenta especially at the decidual interface between mother and fetus supports a role for the diffuse neuroendocrine system (DNES) in the regulation of placental blood flow critical for fetal growth and development.

Calcitonin Gene-Related Peptide↗