Biomedical subjects

V Smith

Publications and source records attributed to V Smith.

At least 37 records · Page 2Linked to original sources

PubMed2001

Unlocking the archive--gene expression in paraffin-embedded tissue.

The histopathology archive represents a vast, well-characterized source of specimens covering virtually every disease and is available for molecular biological investigation. The archive has in recent years become widely used for molecular genetic analysis and DNA can be routinely extracted from formalin-fixed, paraffin-embedded tissue. More recently, archival specimens have become a source of material for extensive analysis of mRNA expression utilizing DNA microarrays, real-time quantitative reverse transcriptase polymerase chain reaction (PCR), and in situ hybridization and amplification techniques. These techniques will enable a greater understanding of the changes that occur in gene function during every stage of the development of disease and will lead to better diagnosis, better evaluation of prognosis, and better treatment through targeted therapeutic regimes.

Biological Specimen Banks↗

PubMed2001

An introduction to arrays.

DNA microarrays are a new technology that allows the analysis of large numbers of genes at a high resolution by the hybridization of labelled DNA, which may be reverse-transcribed from mRNA, to a substrate containing thousands of spotted cDNAs or oligonucleotides. The amount of hybridized target is analysed, giving information on gene expression, polymorphisms or mutations present and allowing the gene profiling of different subtypes of disease. This technique has massive implications for the further understanding of the complicated genetic alterations involved in tumourigenesis and other disease processes and also for the generation of accurate prognostic information and optimization of treatment in these situations.

Computational Biology↗

PubMed2001

Technetium-99 in the Irish marine environment.

Technetium-99 activity concentrations in seawater and biota from Irish coastal waters are presented. Time series measurements of 99Tc in seawater and Fucus vesiculosus from the western Irish Sea show that activity concentrations have increased in line with the increase in discharges of 99Tc from Sellafield. The peak in activity concentrations in both seawater and Fucus vesiculosus occurred in 1997 approximately two years after the peak in 99Tc discharges. The highest activity concentration recorded in Fucus vesiculosus showed a 29-fold increase over the mean concentration for the period 1988-1993. Technetium-99 activity concentrations were measured in fish, lobsters, prawns, mussels and oysters landed at major fishing ports on the east and northeast coasts of Ireland between 1996 and 1998. Concentration factors for 99Tc in the brown seaweed Fucus vesiculosus and certain species of fish, crustaceans and molluscs from the Irish Sea were estimated. In general, these concentration factors were higher than those in the literature which were derived from laboratory studies, but agreed well with values which were based on field studies. The mean committed effective doses to Irish typical and heavy seafood consumers due to 99Tc in the period 1996-1998 were 0.061 and 0.24 microSv, respectively.

Animals↗

PubMed2001

Measuring and improving patients' and families' perceptions of care in a system of pediatric hospitals.

BACKGROUND: Shriners Hospitals for Children (SHC) is a network of 22 pediatric specialty hospitals that provide medical care free of charge to children up to 18 years of age and that serve as referral centers for children with complex orthopedic and burn problems. In 1998 the SHC system began using The Picker Institute's Patient and Family Perception of Care inpatient survey throughout its hospitals. SYSTEMWIDE IMPLEMENTATION: A broad-based implementation plan was developed to promote acceptance of the perception of care topic and provide education on performance improvement. In 1999 a work group was formed to prioritize areas for improvement, survey benchmark hospitals, and identify best practices in benchmark hospitals. This work group first focused on the dimensions of Partnership Between Families and Clinicians and Information and Education to the Child. In May 1999 the work group began the task of identifying best practices in these two priority dimensions from the SHC benchmark hospitals. Surveys were submitted to those hospitals, asking what they perceived as being the reasons they scored well in those areas. The results of these surveys were used to identify key practices in these benchmark hospitals that are of significant importance in patient and family perceptions of quality care. NEXT STEPS: The challenge is to facilitate cross-facility interactions to understand and adopt best practices. Focus groups will be conducted to further delineate the dimensions with higher problem scores. The SHC system plans to expand the patient surveys to outpatients, to allow for the evaluation of the full complement of hospital patients.

Burn Units↗

PubMed2001

Megacystis-microcolon-intestinal hypoperistalsis syndrome and the absence of the alpha3 nicotinic acetylcholine receptor subunit.

BACKGROUND & AIMS: The megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare disease of childhood that presents early with intestinal hypoperistalsis, hydronephrosis, and hydroureters. Transgenic mice that lack the alpha3 subunit containing nicotinic acetylcholine (nAChR) have a phenotype similar to that of MMIHS. METHODS: We examined the expression of this subunit in control and MMIHS tissue derived from patients using in situ hybridization (ISH) and immunocytochemistry (ICC). RESULTS: In controls, both techniques showed a wide distribution of alpha3 nAChRs present in ganglion cells, muscle, and epithelium. By contrast, most MMIHS tissue gave negative staining with ISH and variable results with ICC. CONCLUSIONS: These observations are consistent with a lack of alpha3 nAChRs contributing to the pathogenesis of MMIHS.

Abnormalities, Multiple↗

PubMed2001

Characterization of a human colorectal carcinoma cell line with acquired resistance to flavopiridol.

Flavopiridol is a broad-spectrum inhibitor of cyclin-dependent kinases (cdks) and represents the first in this anticancer class to enter clinical trials. In anticipation of the likelihood that, as with other cancer drugs, acquired resistance may limit the drug's efficacy, an acquired resistance model has been established by in vitro drug exposure of the human colon carcinoma cell line HCT116. This stably resistant line, possessing 8-fold resistance to flavopiridol, showed a lack of cross-resistance to the anticancer agents etoposide, doxorubicin, paclitaxel, topotecan, and cisplatin, and notably to other chemical classes of cdk inhibitors: the aminopurines roscovitine and purvalanol A, 9-nitropaullone, and hymenialdisine. Resistance did not seem to be related to differences in the levels of multidrug resistance drug efflux proteins, P-glycoprotein, and MRP1. Moreover, there were no changes in overall drug accumulation between the resistant and sensitive cell lines. Flavopiridol induced cell cycle arrest, apoptosis, and inhibition of retinoblastoma gene product phosphorylation on serine 780 in both parental and resistant lines, but the latter required 8-fold higher concentrations to achieve these effects. Cyclin E protein levels and cyclin E-associated kinase activity were increased in the resistant line, suggesting that overexpression of cyclin E may be the mechanism of resistance to flavopiridol. However, transfection of cyclin E to increase expression of this protein did not result in an increase in resistance to flavopiridol. Thus, up-regulation of cyclin E alone does not seem to cause resistance to this cdk inhibitor.

Antineoplastic Agents↗

PubMed2001

p57(KIP2) expression in normal islet cells and in hyperinsulinism of infancy.

Most cases of hyperinsulinism of infancy (HI) are caused by mutations in either the sulfonylurea receptor-1 (SUR1) or the inward rectifying K(+) channel Kir6.2, two subunits of the beta-cell ATP-sensitive K(+) channel (K(ATP) channel). Histologically, HI can be divided into two major subtypes. The diffuse form is recessively inherited and involves all beta-cells within the pancreas. Focal HI consists of adenomatous hyperplasia within a limited region of the pancreas, and it is caused by somatic loss of heterozygosity (LOH), including maternal Ch11p15-ter in a beta-cell precursor carrying a germ-line mutation in the paternal allele of SUR1 or Kir6.2. Several imprinted genes are located within this chromosomal region, some of which, including p57(KIP2) and IGF-II, have been associated with the regulation of cell proliferation. Using double immunostaining, we examined p57(KIP2) expression in different islet cell types, in control pancreases from different developmental stages (n = 15), and in pancreases from patients with both diffuse (n = 4) and focal HI (n = 9). Using immunofluorescence and computerized image analysis, we quantified IGF-II expression in beta-cells from patients with focal HI (n = 8). Within the pancreas, p57(KIP2) was specifically localized to the endocrine portion. beta-Cells demonstrated the highest frequency of expression (34.9 +/- 2.7%) compared with approximately 1-3% in other cell types. The fraction of beta-cells expressing p57(KIP2) did not vary significantly during development. beta-Cells within the focal lesions did not express p57(KIP2), whereas IGF-II staining inside focal lesions was mildly increased compared with unaffected surrounding tissue. In conclusion, we demonstrate that p57(KIP2) is expressed and is paternally imprinted in human pancreatic beta-cells. Loss of expression in focal HI is caused by LOH and is associated with increased proliferation and increased IGF-II expression. Manipulation of p57(KIP2) expression in beta-cells may provide a mechanism by which proliferation can be modulated, and thus this gene is a potential therapeutic target for reversing the beta-cell failure observed in diabetes.

Cell Nucleus↗

PubMed2001

Allowing small businesses and the self-employed to buy health care coverage through public programs.

The large number of uninsured working Americans and the extent of public support enjoyed by employment-based health insurance argues for a coverage initiative that fosters access to affordable benefits through employment. This proposal, which reflects models in both Massachusetts and Michigan, entails the development of publicly organized and subsidized group health insurance for small firms with low-wage workers. States would provide overall administration and subsidies to both employers and employees. Employers would enroll workers, select insurers, pay premiums, and report data on employment status. The program would be a legislative extension of the State Children's Health Insurance Program (SCHIP), with federal financing to participating states at each respective SCHIP rate. Anti-crowd-out provisions would be included. This program is both administratively and politically feasible. It is also consistent with current thinking regarding public/private partnerships and the desirability of preserving a voluntary employer-sponsored health insurance system.

Adult↗

PubMed2001

Preclinical antitumor activity and pharmacodynamic studies with the farnesyl protein transferase inhibitor R115777 in human breast cancer.

Antitumor and pharmacodynamic studies were performed in MCF-7 human breast cancer cells and companion xenografts with the farnesyl protein transferase inhibitor, R115777, presently undergoing Phase II clinical trials, including in breast cancer. R115777 inhibited growth of MCF-7 cells in vitro with an IC(50) of 0.31 +/- 0.25 microM. Exposure of MCF-7 cells to increasing concentrations of R115777 for 24 h resulted in the inhibition of protein farnesylation, as indicated by the appearance of prelamin A at concentrations >1 microM. After continuous exposure to 2 microM R115777, prelamin A levels peaked at 2 h post drug exposure and remained high for up to 72 h. R115777 administered p.o. twice daily for 10 consecutive days to mice bearing established s.c. MCF-7 xenografts induced tumor inhibition at a dose of 25 mg/kg [percentage of treated versus control (% T/C) = 63% at day 21]. Greater inhibition was observed at doses of 50 mg/kg (% T/C at day 21 = 38%) or 100 mg/kg (% T/C at day 21 = 43%). The antitumor effect appeared to be mainly cytostatic with little evidence of tumor shrinkage to less than the starting volume. Tumor response correlated with an increase in the appearance of prelamin A, but no changes in the prenylation of lamin B, heat shock protein 40, or N-Ras were detectable. In addition, significant increases in apoptotic index and p21(WAF1/CIP1) expression were observed, concomitant with a decrease in proliferation as measured by Ki-67 staining. An increase in prelamin A was also observed in peripheral blood lymphocytes in a breast cancer patient who responded to R115777. These data show that R115777 possesses preclinical antitumor activity against human breast cancer and that the appearance of prelamin A may provide a sensitive and convenient pharmacodynamic marker of inhibition of prenylation and/or response.

Alkyl and Aryl Transferases↗

PubMed2000

Evaluation of the CatanDog's tag to prevent flea infestations, inhibit flea reproduction or repel existing flea infestations on cats.

To evaluate the ability of the CatanDog's tag to eliminate fleas, inhibit egg production and prevent flea infestations, six domestic shorthaired cats were randomly allocated to two treatment groups and housed individually in stainless steel metabolic cages. Three cats were each fitted with a CatanDog's tag; the other three cats were not fitted with tags and served as controls. Following a 42-day acclimation period, each of the six cats was infested with 100, 1-3 day post-emergence, adult Ctenocephalides felis felis (Bouché) on days 0, 7, 14, 21, and 27. Flea egg production was determined by collecting and enumerating eggs 2, 4 and 6 days after each infestation. Viability of eggs was determined by placing 100 eggs recovered from each cat in rearing media in an insect rearing chamber and determining adult emergence at 28 days. Adult fleas were recovered from cats 6 days post-infestation by thoroughly combing each cat to remove fleas. To determine if the tags provided protection from infestation, the six cats were placed into a 8.53mx4.36 m room with 400 cat fleas for 3h. Cats were then combed to remove and enumerate fleas. The CatanDog's tags had no significant effect upon egg production, egg viability, or adult fleas infesting cats. In addition there was no difference in the numbers of fleas recovered from the cats placed in the flea-infested room.

Animals↗

PubMed2000

Systemic adoptive T-cell immunotherapy in recurrent and metastatic carcinoma of the head and neck: a phase 1 study.

OBJECTIVE: To evaluate the feasibility and toxic effects of systemic adoptive T-cell immunotherapy in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN). DESIGN: Nonrandomized phase 1 clinical trial. SETTING: Academic tertiary care hospital. PATIENTS: Between April 1, 1996, and September 30, 1998, 17 patients with confirmed recurrent and metastatic SCC of the upper aerodigestive tract were enrolled. Two patients did not receive T cells because of poor vaccine response. Fifteen patients were successfully treated with T-cell immunotherapy. INTERVENTION: Patients were vaccinated on the thigh with irradiated autologous tumor cells admixed with granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by 3 additional daily injections of GM-CSF at the vaccination site. Eight to 10 days later, tumor cell vaccine-draining inguinal lymph nodes were resected, and lymph node lymphocytes were activated with staphylococcal enterotoxin A and expanded in interleukin 2 in vitro. Resulting cultured cells were infused into patients peripherally on an outpatient basis. RESULTS: Toxic effects of infusion were limited to grade 2 reactions in 3 of 16 treatments. One patient required overnight hospitalization for fever and emesis. Median cell expansion was 37 times (range, 4-416 times), and median cell dose was 7.5 x 10(9) (range, 1.3 x 10(8) to 4.2 x 10(10)). Infused cells were predominantly CD3+ (>97%), being a mixture of CD4+ and CD8+ cells. Three patients demonstrated stabilization of previously progressive disease. Two patients experienced favorable clinical courses after adoptive T-cell transfer, including 1 patient with no evidence of disease 4 years after surgical resection of a vertebral body metastasis. CONCLUSIONS: Adoptive immunotherapy is a technically feasible and safe treatment with low toxicity and may demonstrate therapeutic activity in patients with unresectable SCCHN.

Adult↗

PubMed2000

Race- and sex-specific ECG models for left ventricular mass in older populations. Factors influencing overestimation of left ventricular hypertrophy prevalence by ECG criteria in African-Americans.

The validity of the reported high prevalence of left ventricular hypertrophy (LVH) among African-American men and women has been questioned owing to conflicting echocardiographic evidence. We used echocardiographic left ventricular mass (LVM) from M-mode measurements to evaluate associations between LVM, body size, and electrocardiographic (ECG) variables in 3,627 white and African-American men and women 65 years of age and older who were participants of the Cardiovascular Health Study (CHS), a multicenter cohort study of risk factors for coronary heart disease and stroke. ECG amplitudes used in LVH criteria were substantially higher in African-Americans, with apparent LVH prevalence 2 to 3 times higher in African American men and women than in white men and women, although there was no significant racial difference in echocardiographic LVM. The higher apparent LVH prevalence by Sokolow-Lyon criteria in African-American men is in part owing to smaller lateral chest diameter. In women, reasons for racial differences in ECG LVH prevalence remain largely unexplained although a small part of the excess LVH in African-American women by the Sokolow-Lyon criteria appears to be owing to a larger lateral chest semidiameter in white women. ECG variables alone were too inaccurate for LVM prediction, and it was necessary to incorporate in all ECG models body weight that was properly adjusted for race and sex. This resulted in modest LVM prediction accuracy, with R-square values ranging from .22 to .36. Race- and sex-specific ECG models introduced for LVM estimation with an appropriate adjustment for body size differences are expected to facilitate evaluation of LVH status in contrasting racial population groups.

Age Factors↗

PubMed2000

A new method of evaluating attachment representations in young school-age children: the Manchester Child Attachment Story Task.

We describe a new instrument, using a doll-play vignette completion method, which applies concepts and methodologies from infant and adult attachment research to enable identification and detailed classification of internal representations of attachment relationships in young school-age children. Validation of the Manchester Child Attachment Story Task (MCAST) in a normal population (N = 53) shows good interrater reliability and content validity. Patterns of attachment representation identified show stability over time. Comparisons are made with existing methodologies, and potential applications of the instrument and directions for future research are discussed.

Child↗

PubMed2000

The Manchester Child Attachment Story Task: relationship with parental AAI, SAT and child behaviour.

The Manchester Attachment Story Task (MCAST) is a new method for eliciting the internal working model (IWM) of attachment representations in children between 5 and 7 years. The instrument is described in the companion paper, 'A New Method of Evaluating Attachment Representations'. This paper reports initial findings on a non-clinical sample comparing the MCAST with concurrent maternal attachment representation, measures of child temperament and behaviour, and concurrent ratings on the Separation Anxiety Test (SAT). Ratings of disorganized attachment on the MCAST show association with Unresolved status on concurrent maternal Adult Attachment Interview (AAI) and with independent teacher ratings of classroom behaviour. Child temperament shows an effect on the style of engagement with the interview but not the attachment ratings. Possible alternative explanations for the phenomena seen are discussed, along with potential applications of the instrument and directions for future research.

Anxiety, Separation↗

PubMed2000

Spondylometaphyseal dysplasia Sedaghatian type associated with lethal arrhythmia and normal intrauterine growth in three siblings.

Spondylometaphyseal dysplasia of the Sedaghatian type is a rare dysplasia, characterized by mild limb shortening, but lethal in the neonatal period. We describe three affected male siblings, the offspring of consanguineous parents. One was stillborn. Neonatal death was due to cardiac arrhythmia in two of the siblings. This report confirms the importance of cardiac pathology in this probably autosomal recessive disorder. This diagnosis should be excluded in any newborn with an arrhythmia as the clinical limb shortening may not be obvious.

Arrhythmias, Cardiac↗

PubMed2000

Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory.

The Neuropsychiatric Inventory (NPI) is a validated clinical instrument for evaluating psychopathology in dementia. The authors developed a brief questionnaire form of the NPI (NPI-Q), intended for use in routine clinical practice, and cross-validated it with the NPI in 60 Alzheimer's patients. Test-retest reliability of the NPI-Q was acceptable. The prevalence of analogous symptoms reported on the NPI and NPI-Q differed on average by 5%; moderate or severe symptom ratings differed by less than 2%. The NPI-Q provides a brief, reliable, informant-based assessment of neuropsychiatric symptoms and associated caregiver distress that may be suitable for use in general clinical practice.

Aged↗

PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗

PubMed2000

Endoscopic thoracoplasty and anterior spinal release in scoliotic deformity.

Severe rigid and complex deformities of the spine often require a first stage procedure to adequately mobilize the spine to provide adequate flexibility during the actual application of instrumentation for surgical correction. This first stage involves soft tissue releases and removal of intervertebral disks from the anterior spine. Exposure to the anterior spine has traditionally been accomplished through thoracotomy or a thoracolumbar incision. The open thoracotomy, however, has several disadvantages, such as post-thoracotomy pain, a large scar, and breathing difficulties. Since the first thoracoscopy at the beginning of this century, the procedure, at first limited by the available technology, has gradually gained more uses and favor among physicians. The last 10 years have seen significant improvement in optical technology and instrumentation. These advances have allowed the spine surgeon to begin performing anterior spinal releases using endoscopic techniques. These endoscopic techniques can carry the same efficacy as the open thoracotomy but less morbidity. Thoracoplasty, the resection of rib segments, is an excellent way to not only correct the convex rib deformities seen in scoliosis but it is also an excellent source of bone which can be used as a graft for fusion. Although traditionally, thoracoplasty has also been done through an open procedure, it can be performed endoscopically. This prospective study presents nine patients who underwent combined endoscopic anterior spinal release and thoracoplasty followed by same day posterior instrumentation and fusion for correction of their spinal deformities. All nine procedures were completed successfully endoscopically. It is our conclusion that in the hands of an experienced surgeon, the endoscopic technique is an excellent procedure providing the same efficacy as the open thoracotomy. There is however a learning curve associated with the procedure. In addition, a team approach in which the surgeon and an experienced anesthesiologist with experience with double lumen intubation and selective single lung ventilation and thoracoscopic surgery is crucial. Although there were no surgical complications related to the thoracoscopic technique one patient did require prolonged intubation postoperatively, which leads us to believe that single lung ventilation in and of itself is very demanding and each patient must be considered carefully prior to its undertaking.

Adolescent↗