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Biomedical subjects

L Smith

Publications and source records attributed to L Smith.

At least 235 records · Page 13Linked to original sources

Critical thinking, health policy, and the Hmong culture group, Part II.

The Hmong are an Asian cultural group originating primarily in the northern hills of Laos. During the Vietnam conflict, they fought and died for the U.S. during a secret Laotian war. The U.S. gained their support in exchange for protecting them from their enemies in Laos regardless of the war's outcome. When North Vietnam took over Laos, hundreds of thousands of Hmong fled to Thailand's refugee camps; from there, over 100,000 Hmong refugees relocated to the U.S. (Heu, 1996). With them, the Hmong brought culture, language, and healthcare beliefs and rituals, as well as distinct challenges to U.S. communities, policy makers, and healthcare professionals. This article is the second in a two-part series on critical thinking and health policy and the Hmong culture group.

Acculturation↗

Pathologic features of rhabdomyosarcoma before and after treatment: a clinicopathologic and immunohistochemical analysis.

Few studies have analyzed the relationship among pathology, therapy-induced changes, proliferative activity, and outcome for rhabdomyosarcoma (RMS), despite the challenges of histopathologic interpretation of this tumor after treatment. Although cytodifferentiation and decreased mitotic activity after treatment were documented previously, the clinical consequences of these changes are uncertain because of the small number of cases analyzed. We analyzed 16 RMSs with pre- and post-treatment specimens for clinicopathologic features, outcome, and immunohistochemical data on formalin-fixed, paraffin-embedded tissue for vimentin, smooth muscle actin, muscle-specific actin, desmin, myoglobin, p53 protein, topoisomerase II-alpha, and MIB-1 proliferative activity. Four of eight alveolar (ARMS), five of five botryoid (BRMS), and two of three nonbotryoid embryonal (ERMS) RMSs displayed varying degrees of post-therapeutic histologic maturation and expressed one or more myoid markers. The remaining five RMSs had no cytodifferentiation. Myoid marker expression did not change significantly. In BRMS, MIB-1 and topoisomerase II-alpha proliferative activity decreased after therapy and correlated with cytodifferentiation and survival. This relationship was less clear for ERMS and ARMS. Five nonbotryoid RMSs without cytodifferentiation had either unchanged or increased proliferative activity, and four of these patients died of RMS. Six nonbotryoid RMSs with both cytodifferentiation and residual foci of undifferentiated cells had variable outcomes, including longer survival. We conclude that BRMS and ERMS exhibit therapy-induced cytodifferentiation more frequently than does ARMS. Cytodifferentiation and decreased proliferative activity are associated with favorable outcome in BRMS; unchanged or increased post-therapeutic proliferative activity suggests aggressive biologic potential in ERMS and ARMS. Combined patterns of cytodifferentiation and residual undifferentiated foci might be associated with increased, decreased, or unchanged proliferative activity and are difficult to interpret, but the presence of cytodifferentiation might presage an improved survival. Immunohistochemical analysis for proliferation markers might be useful for highlighting foci of less differentiated RMS or cytodifferentiated tumor cells in contrast to non-neoplastic, terminally differentiated muscle cells.

Actins↗

Effects on Accidents of Time into Shift and of Short Breaks between Shifts.

This study aimed to determine whether there was a peak in accidents in the second to fourth hours within a shift and to compare the effect on accidents of the presence or absence of a break of only eight hours between shifts in a shift cycle ("quick returns"). Archival accident records were obtained for a four-year period from two sister works within the same division of a heavy-industrial organization. The works had many similarities but differed in the shift systems used. One had "quick returns," whereas the other did not. Accident frequencies were analyzed across four variables, site, shift, time on shift, and process code (process code identified the process area in which the worker operated). These were analyzed by hierarchical log-linear analysis, using a significance level of 0.05. The results indicated there was a peak in accidents in the second and third hours into a shift, but provided only slight evidence for a detrimental effect of "quick returns."

Journal Article↗

Introducing change to the post-anaesthetic care unit.

Parental presence in the post-operative care unit (PACU) is an under-reported and under-researched area of paediatric care. This article explores the importance and value of parents being present with their child post-operatively. It reports on the audit findings following a practice development project which encouraged parents to be with their child in the PACU.

Child↗

Reverse transcriptase mutations in HIV-1-infected children treated with zidovudine.

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutations were detected in DNA from peripheral blood mononuclear cells from 11 of 12 HIV-1-infected children after 11-20 months of zidovudine monotherapy. The number of children with mutations detected at each codon were as follows: codon 41, 4; codon 67, 2; codon 70, 7; codon 215, 7; codon 219, 0. Codon 41 mutations were found only in the presence of a codon 215 mutation and in the absence of a codon 70 mutation. The codon 41/215 mutant combination was associated with decline in weight-for-age z score during therapy, weight < 10th percentile, CD4+ cell counts < 3rd percentile, and immune-complex dissociated HIV-1 p24 antigen (ICD p24 Ag) levels > 100 pg/ml. Patients developing the codon 70 mutation tended to have body weight > 30th percentile, CD4+ cell counts > 25th percentile, and ICD p24 Ag < 100 pg/ml. The codon 41 mutation was associated with clinical deterioration during a 6-month followup period.

Anti-HIV Agents↗

Blunt popliteal artery injuries.

AIMS: To survey the recent results of vascular damage resulting from knee injuries at Middlemore Hospital. METHOD: A group of sixteen patients treated between 1980-92 were retrospectively analysed. RESULTS: One patient failed a grafting procedure and required a below knee amputation. Another patient lost two muscle compartments with its associated disability, as a result of pressure necrosis from the acute compartment syndrome. The remaining patients were successfully revascularised. CONCLUSION: Unless revascularisation is quickly achieved popliteal artery damage associated with knee injuries will lead to frequent leg amputation.

Adolescent↗

The RNA world of the nucleolus: two major families of small RNAs defined by different box elements with related functions.

We have discovered that all known yeast and vertebrate small nucleolar RNAs (snoRNAs), except for the MRP/7-2 RNA, fall into two major classes. One class is defined by conserved boxes C and D and the other by a novel element: a consensus ACA triplet positioned 3 nt before the 3' end of the RNA. A role for the ACA box is snoRNA stability has been established by mutational analysis of a yeast ACA snoRNA (snR 11). Full function of the box depends on the integrity of an adjacent upstream stem. All members of the yeast ACA family are associated with the GAR1 protein. Binding of this or another common small nucleolar ribonucleoprotein particle protein is predicted to be a critical entry point to snoRNA posttranscriptional life, including precise formation of the snoRNA 3' end.

Animals↗

Ubiquitination of protein kinase C-alpha and degradation by the proteasome.

Bryostatins and phorbol esters acutely activate and subsequently down-regulate protein kinase C (PKC) by inducing its proteolysis via an unknown pathway. Here we show that treatment of renal epithelial cells with bryostatin 1 (Bryo) produced novel PKC-alpha species, which were larger than the native protein (80 kDa). The >80 kDa PKC-alpha species contained Ubi as indicated by immunostaining and accumulated in the presence of lactacystin, a selective inhibitor of proteolysis by the proteasome. In vitro experiments with 125I-ubiquitin and membranes from Bryo-treated cells showed that PKC-alpha became ubiquitinated by a reaction that depended on ATP and a cytosolic fraction. Lactacystin or a peptidyl aldehyde, Bz-Gly-Leu-Ala-leucinal, which inhibits certain proteinase activities of the proteasome, inhibited Bryo-evoked disappearance of PKC-alpha protein from the cells. Lacta preserved Bryo-induced 32P-labeled PKC-alpha indicating that the proteasome inhibitor spared activated enzyme from down-regulation in vivo. These findings show that Bryo induces the degradation of PKC-alpha by the ubiquitin-proteasome complex.

Acetylcysteine↗

An approach to investigating linkage for bipolar disorder using large Costa Rican pedigrees.

Despite the evidence that major gene effects exist for bipolar disorder (BP), efforts to map BP loci have so far been unsuccessful. A strategy for mapping BP loci is described, focused on investigation of large pedigrees from a genetically homogenous population, that of Costa Rica. This approach is based on the use of a conservative definition of the BP phenotype in preparation for whole genome screening with polymorphic markers. Linkage simulation analyses are utilized to indicate the probability of detecting evidence suggestive of linkage, using these pedigrees. These analyses are performed under a series of single locus models, ranging from recessive to nearly dominant, utilizing both lod score and affected pedigree member analyses. Additional calculations demonstrate that with any of the models employed, most of the information for linkage derives from affected rather than unaffected individuals.

Bipolar Disorder↗

Mapping of the ARIX homeodomain gene to mouse chromosome 7 and human chromosome 11q13.

The recently described homeodomain protein ARIX is expressed specifically in noradrenergic cell types of the sympathetic nervous system, brain, and adrenal medulla. ARIX interacts with regulatory elements of the genes encoding the noradrenergic biosynthetic enzymes tyrosine hydroxylase and dopamine beta-hydroxylase, suggesting a role for ARIX in expression of the noradrenergic phenotype. In the study described here, the mouse and human ARIX genes are mapped. Using segregation analysis of two panels of mouse backcross DNA, mouse Arix was positioned approximately 50 cM distal to the centromere of chromosome 7, near Hbb. Human ARIX was positioned through analysis of somatic cell hybrids and fluorescence in situ hybridization of human metaphase chromosomes to chromosome 11q13.3-q13.4. These map locations extend and further define regions of conserved synteny between mouse and human genomes and identify a new candidate gene for inherited developmental disorders linked to human 11q13.

Animals↗

Levels of soluble cell adhesion molecules in patients with dyslipidemia.

BACKGROUND: Increased expression of cell adhesion molecules (CAMs) on the vascular endothelium has been postulated to play an important role in atherogenesis. Both in vitro and in vivo studies have suggested that dyslipidemia may increase expression of CAMs. METHODS AND RESULTS: To determine whether dyslipidemia is associated with increased expression of CAMs, we examined the levels of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and soluble E-selectin (sE-selectin) in individuals with either hypercholesterolemia or hypertriglyceridemia and in control subjects matched for age and sex. Patients with hypertriglyceridemia had significantly higher levels of sVCAM-1 (739 +/- 69 ng/mL) compared with patients with hypercholesterolemia (552 +/- 63 ng/mL) and control subjects (480 +/- 56 ng/mL). Levels of sICAM-1 were significantly increased in both the hypercholesterolemic and hypertriglyceridemic groups (298 +/- 29 and 342 +/- 31 ng/mL, respectively) compared with the control group (198 +/- 14 ng/mL). Levels of sE-selectin were significantly increased in hypercholesterolemic patients (74 +/- 9 ng/mL) compared with control subjects (48 +/- 5 ng/mL). Ten hypercholesterolemic patients were treated aggressively with atorvastatin alone or a combination of colestipol and either atorvastatin or simvastatin for a mean of 42 weeks and had an average LDL cholesterol reduction of 51%. Comparison of soluble CAMs before and after treatment showed a significant reduction only in sE-selectin (77 +/- 11 versus 56 +/- 6 ng/mL, P < or = .03) but not for sVCAM-1 or sICAM-1. CONCLUSIONS: Although severe hyperlipidemia is associated with increased levels of soluble CAMs, aggressive lipid-lowering treatment had only limited effects on the levels. Increased levels of soluble CAMs in patients with hyperlipidemia may be a marker for atherosclerosis.

Anticholesteremic Agents↗

General practitioners' management of acute back pain: a survey of reported practice compared with clinical guidelines.

OBJECTIVE: To compare general practitioners' reported management of acute back pain with 'evidence based' guidelines for its management. DESIGN: Confidential postal questionnaire. SETTING: One health district in the South and West region. SUBJECTS: 236 general practitioners; 166 (70%) responded. OUTCOME MEASURES: Examination routinely performed, 'danger' symptoms and signs warranting urgent referral, advice given, and satisfaction with management. RESULTS: A minority of general practitioners do not examine reflexes routinely (27%, 95% confidence interval 20% to 34%), and a majority do not examine routinely for muscle weakness or sensation. Although most would refer patients with danger signs, some would not seek urgent advice for saddle anaesthesia (6%, 3% to 11%), extensor plantar response (45%, 37% to 53%), or neurological signs at multiple levels (15%, 10% to 21%). A minority do not give advice about back exercises (42%, 34% to 49%), fitness (34%, 26% to 41%), or everyday activities. A minority performed manipulation (20%) or acupuncture (6%). One third rated their satisfaction with management of back pain as 4 out of 10 or less. CONCLUSIONS: The management of back pain by general practitioners does not match the guidelines, but there is little evidence from general practice for many of the recommendations, including routine examination, activity modification, educational advice, and back exercises. General practitioners need to be more aware of danger symptoms and of the benefits of early mobilisation and possibly of manipulation for persisting symptoms. Guidelines should reference each recommendation and discuss study methodology and the setting of evidence.

Acute Disease↗