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Biomedical subjects

C H Smith

Publications and source records attributed to C H Smith.

At least 37 records · Page 2Linked to original sources

A randomized comparison of 4 weeks of terbinafine vs. 8 weeks of griseofulvin for the treatment of tinea capitis.

BACKGROUND: Tinea capitis is a common childhood infection that has recently become more frequent in urban areas in Europe and the U.S.A. The current licensed treatment in children is griseofulvin 10 mg kg(-1) daily, which is usually given for 6--8 weeks. OBJECTIVES: To compare this treatment with a 4-week course of oral terbinafine. METHODS: Terbinafine was given at the following doses: in children weighing < 20 kg, 62.5 mg daily; 20--40 kg, 125 mg daily; > 40 kg, 250 mg daily. Two hundred and ten children aged 2--16 years, with mycologically confirmed tinea capitis, were randomized to 4 weeks treatment with terbinafine or 8 weeks with griseofulvin, and followed for a total of 24 weeks to determine the difference between treatments with respect to short- and long-term efficacy and tolerability. RESULTS: One hundred and forty-seven patients were evaluable (terbinafine 77, griseofulvin 70). Although the 4-week course of terbinafine resulted in a trend to more rapid clearance of tinea capitis, there were no statistically significant differences between the two drugs in terms of overall outcome or tolerability, apart from in a subgroup of patients with Trichophyton infections, and weighing > 20 kg, who responded better to terbinafine than to griseofulvin at 4 weeks. By contrast, there was a better response to griseofulvin than to terbinafine in patients with Microsporum audouinii infections. CONCLUSIONS: Overall, the study showed that 4 weeks of treatment with oral terbinafine has similar efficacy to 8 weeks of treatment with griseofulvin for the management of tinea capitis in children.

Adolescent↗

Laparoscopic repair of a ruptured diaphragm secondary to blunt trauma.

The diagnosis of acute diaphragmatic rupture can be a challenge for even the most experienced clinician. The treatment of the rupture and its concomitant injuries, particularly in the elderly, can be associated with significant morbidity and mortality. The advent of laparoscopy for both the diagnosis and repair of this condition has allowed a more minimally invasive approach. We present the case of a 70-year-old woman who was hurt in a motor vehicle crash. On admission, her physical exam showed left upper quadrant tenderness and bruising. The chest radiograph was suggestive of a ruptured diaphragm. She was taken to the operating room and explored laparoscopically. After a thorough exploration of all the abdominal contents, a tear in the diaphragmatic hiatus to the right of the esophagus was noted. The stomach and small intestine were returned to the abdomen, and the diaphragmatic rupture was repaired. We conclude that laparoscopic exploration and repair of a ruptured diaphragm in a bluntly injured patient is a safe and effective option in selected cases.

Accidents, Traffic↗

Transactivation of a target gene through feedforward loop activation in plants.

The expression of many genes encoding transcriptional activators in prokaryotes and eukaryotes is upregulated through positive feedback activation. During positive feedback activation, a transcriptional activator binds to its own promoter and thus increases its own expression as well as the expression of its target genes. In the simplest case, increased levels of the transcriptional activator can be directly correlated with increased expression of its target genes. In this study, we present a gene expression system, designated feedforward loop (FFL) system, which makes use of this kind of positive feedback regulation for the expression of plant transgenes. We show in transient and stable transformation experiments that such a system is functional and that it can be used to obtain high level gene expression in plants. We also provide evidence that the transgene is ubiquitously expressed when using the FFL system. Finally, we discuss the possibilities of using FFL gene expression systems for applications in plant molecular genetics and biotechnology.

Agrobacterium tumefaciens↗

Temporal and biomechanical characteristics of oropharyngeal swallow in younger and older men.

As the U.S. population ages, there is increasing need for data on the effects of aging in healthy elderly individuals over age 80. This investigation compared the swallowing ability of 8 healthy younger men between the ages of 21 and 29 and 8 healthy older men between the ages of 80 and 94 during two swallows each of 1 ml and 10 ml liquid. Videofluoroscopic studies of these swallows were analyzed to confirm the absence of swallowing disorders. Biomechanical analysis of each swallow was completed, from which data on temporal, range of motion, and coordination characteristics of the oropharyngeal swallow were taken. Position of the larynx at rest, length of neck, and pattern of hyoid bone movement were also compared between the two groups. None of the younger or older men exhibited any swallowing disorders. The C2 to C4 distance of older men was significantly shorter than that of younger men, and laryngeal position at rest was lower than in younger men but not significantly so. Older men had a significantly longer pharyngeal delay than younger men and significantly faster onset of posterior pharyngeal wall movement in relation to first cricopharyngeal opening. The older men exhibited significantly reduced maximum vertical and anterior hyoid movement as compared to the younger men even when accounting for the difference in C2 to C4 distance in older men. These data support the hypothesis of reduced muscular reserve in the swallows of older men as compared to younger men. Older men also exhibited less width of cricopharyngeal opening than younger men at 10 ml volume, indicating less upper esophageal sphincter flexibility in the swallows of older men. The potential for exercise to improve reserve is discussed. Significant changes in extent of hyoid elevation and duration of cricopharyngeal opening were seen as liquid bolus volume increased.

Adult↗

Guidelines for the management of tinea capitis. British Association of Dermatologists.

These guidelines for the management of tinea capitis have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.

Antifungal Agents↗

New approaches to topical therapy.

Despite the rapid and proven efficacy of topical corticosteroids, side-effects can limit their clinical usefulness. Topically active macrolide immunosuppressants such as ascomycin and tacrolimus appear to provide comparable therapeutic potency without significant local or adverse effects. Data from ongoing studies will be crucial in determining the safety of these agents in the long term, and also their place within the current therapeutic armamentarium available for patients with atopic dermatitis. Enzyme inhibitors of PLA(2) and PDE 4 currently in the very early stages of clinical development also show potential promise as additional alternative strategies to topical treatment and may perhaps act as steroid sparing agents. Having been in the therapeutic doldrums for years, topical management of atopic dermatitis is likely to show great changes in the very near future.

Administration, Topical↗

A double blind, randomized, controlled clinical trial to assess the efficacy of a new coal tar preparation (Exorex) in the treatment of chronic, plaque type psoriasis.

Exorex is a new topical formulation for the treatment of psoriasis; it contains 1% coal tar and a synthetic analogue resembling components identified in banana skin (a complex of esterified essential fatty acids). To determine whether the esterified essential fatty acid complex confers any therapeutic advantage over coal tar alone, patients with chronic plaque psoriasis (n = 20) were entered into a double-blind, randomized, right/left comparison of Exorex, and Exorex without the essential fatty acid component (known hereafter as coal tar control) for 8 weeks. Target plaques were scored (0-4) for erythema, desquamation and infiltration at day 0 and at 2 week intervals throughout the study. No significant differences were detected between Exorex and coal tar control with respect to changes in the summed scores at baseline and following 8 weeks of treatment (mean difference in summed score changes from baseline between Exorex and coal tar control 0.2, 95% confidence interval - 0.44 to 0.84; P = 0.52) or in the area under the response-time curve (P = 0.16). Mean percentage improvement in summed scores of target plaques were 53.9% (SE = 4%) and 56.1% (SE = 4.9%) for Exorex and coal tar control, respectively. Results suggest that the complex of esterified essential fatty acids is not exerting any clinically important therapeutic effect in the treatment of chronic plaque psoriasis.

Administration, Topical↗

Polarized distribution of interleukin-1 receptors and their role in regulation of serotonin transporter in placenta.

We investigated the expression of interleukin-1 (IL-1) receptors and their involvement in the regulation of the serotonin transporter gene expression in human placenta. IL-1beta is an activator of the serotonin transporter gene expression in JAR human placental choriocarcinoma cells as demonstrated by an increase in the steady-state levels of the transporter mRNA and in serotonin transport activity. This activation is blocked by IL-1 receptor antagonist. Genistein also blocks the effect of IL-1beta, indicating involvement of tyrosine phosphorylation in the process. Treatment of JAR cells with IL-1beta activates mitogen-activated protein kinases and nuclear factor-kappaB. The nuclear factor-kappaB that is responsive to IL-1beta in these cells is the p65 homodimer. Northern blot analysis and reverse transcription-polymerase chain reaction revealed that JAR cells and human placenta express type I and type II IL-1 receptors. The binding sites for (125)I-IL-1beta are localized predominantly in the maternal-facing brush border membrane of the syncytiotrophoblast. These results show that IL-1 in the maternal circulation is likely to play a critical role in the regulation of the serotonin transporter gene expression in the placenta.

Carrier Proteins↗

Identification of three cationic amino acid transporters in placental trophoblast: cloning, expression, and characterization of hCAT-1.

The concentrative transfer of amino acids from maternal to fetal blood is essential to fetal growth and metabolism. Cationic amino acids are transported across the placental microvillous and basal membranes by multiple pathways which act to mediate maternal/fetal transport. To identify the cationic amino acid transporters of human placenta, total RNA was harvested from cultured trophoblast and from the BeWo choriocarcinoma cell line, b30 clone, and used for reverse transcription (RT) and polymerase chain reaction (PCR). Primers based on published sequences identified expression of mRNAs for hCATs-1, -2B, and -4. RT-PCR yielded a 2.1 kb hCAT-1 cDNA which was cloned. hCAT-1 cRNA injection into Xenopus laevis oocytes stimulated saturable lysine uptake (K(m) approximately 100 microM). In the presence of Na(+), uptake was inhibited by leucine, homoserine, and alanine but not by valine and glutamate. These transport characteristics are comparable to those of system y(+) in placental basal membrane, but differ from those of the same system in microvillous membrane. The identification, cloning, and characterization of multiple human placental cationic amino acid transporters has the potential to facilitate molecular investigation of transport by the maternal- and fetal-facing membranes of placental trophoblast and increase understanding of the mechanism of transplacental amino acid transfer.

Amino Acid Transport Systems, Basic↗

Incidence and patient characteristics associated with silent aspiration in the acute care setting.

Coughing is a physiologic response to aspiration in normal healthy individuals. However, there are published records that report no cough in response to aspiration (i.e., silent aspiration) in dysphagic patients. In this retrospective study, for more than 2 years in two acute care hospitals we examined frequency of the cough response in patients identified as aspirators by using videofluoroscopy. One thousand one hundred one patients underwent videofluorographic evaluation of their swallowing during this 2-year period; 469 aspirated; 276 were silently aspirating. Two hundred twenty-four of these silent aspirators aspirated once during a swallow and 52 silently aspirated more than once during a swallow. These two groups of patients were analyzed separately. Univariate (chi-square and Fisher's exact tests) and multivariate (logistic regression) analyses were conducted to assess the relationship of silent aspiration to age, gender, medical diagnosis, timing of aspiration, and etiology of aspiration. In univariate analysis, age (p < 0.001), gender (p < 0.004), and medical diagnosis (p = 0.05) were significantly associated with silent aspiration in the group who aspirated once during a swallow. No significant associations were seen in the group of patients who aspirated more than once during a swallow.

Adolescent↗

Factors related to dropout in a study of head and neck cancer patients after surgery.

The extent and nature of dropout was assessed in a longitudinal study whose objective was to define and quantify the functional effects of oral surgical resection and reconstruction on speech and swallowing function in patients with head and neck cancer. Of 150 patients who were enrolled to be followed up with speech and swallow assessments for 1 year after surgery, 113 (75%) dropped out and 37 (25%) returned to complete the study at the final 12-month evaluation point. In general, those completing the study had a smaller resection than the patients who dropped out before the 12-month evaluation. Fifty percent of the dropout was accounted for by medical reasons, 23% by administrative reasons, and 27% by patient-specific reasons (i.e., reasons known only to the patient). Analysis of the dropout categories revealed that higher cancer stage, larger volume of resection, and having a flap surgical closure versus a primary closure or skin graft increased a patient's chance of dropping out. A larger volume of resection was also related to an increased chance of being a patient-specific dropout. Patients who reported no or low alcohol usage had a greater chance of completing follow-up than being a patient-specific dropout.

Adult↗

Relating speech and swallow function to dropout in a longitudinal study of head and neck cancer.

The relation between functional outcome and dropout from a 12-month follow-up period was examined in a longitudinal study whose objective was to define and quantify the functional effects of oral surgical resection and reconstruction on speech and swallowing in patients with head and neck cancer. In a group of 150 patients recruited to a surgical study in the Cancer Control Science Program in Head and Neck Cancer Rehabilitation, dropout from all causes and dropout from specific causes (medical, patient, and administrative specific) were assessed in relation to longitudinal speech and swallow function. In univariate analysis, better speech articulation was associated with decreased risk of dropout from all causes and from medical-specific causes. Better swallow performance was associated with decreased risk of medical-specific dropout. Multivariate analysis revealed the following: (1) only articulation function was associated with dropout from all causes; (2) the association of speech articulation function with medical dropout was diminished after adjusting for advanced age and surgical resection variables; (3) the association of speech articulation function became significant for patient-specific dropout after adjusting for advanced age and surgical resection variables and indicated that better function decreased the risk of this type of dropout; and (4) swallowing function was not related to dropout. Patients treated for oral or oropharyngeal cancer who have poorer speech outcomes are more likely to drop out from a longitudinal study. Basing study results on only patients who complete a longitudinal study will understate the level of dysfunction experienced.

Adult↗

IGF binding protein-1 (IGFBP-1) is preferentially associated with the fetal-facing basal surface of the syncytiotrophoblast in the human placenta.

IGF receptors are expressed in a spatially polarized manner on the syncytiotrophoblast cell membrane. We therefore examined the hypothesis that IGFBPs expressed at the maternal-fetal interface interact with distinct surfaces of the syncytiotrophoblast membrane to modulate IGF function. Membrane vesicles were prepared specifically from the maternal-facing, microvillous membrane (MVM) and the fetal-facing, basal membrane (BM) surfaces of the syncytiotrophoblast. The association of IGFBPs with each membrane preparation was determined by ligand blot analysis. A doublet migrating at 38/42 kD was detected in both MVM and BM preparations. Selective immunoprecipitation followed by ligand blot analysis identified this IGF binding species as IGFBP-3. Additionally, a protein migrating at approximately 29 kD was associated primarily with the BM. This protein was identified as IGFBP-1 by both immunoprecipitation and ligandblotting techniques. Non-denaturing PAGE revealed five distinct bands corresponding to different degrees of phosphorylation. The phosphorylation pattern of BM-associated IGFBP-1 was identical to that of native IGFBP-1 in amniotic fluid. Immunohistological analysis of term placenta revealed IGFBP-1-specific staining of the syncytiotrophoblast and the fetal capillary/pericapillary bed. The localization of IGFBP-1 to a distinct compartment within the fetal placenta, not in proximity to the syncytiotrophoblast type I IGF receptor, suggests it may play a role in regulating/targeting IGF activity within the stromal compartment or by exerting IGF-independent effects on the basal surface of the syncytiotrophoblast. The nature of its binding to the BM has not been determined.

Female↗

Bedside insertion of inferior vena cava filters in the intensive care unit.

BACKGROUND: Injured patients are at significant risk for venous thromboembolic complications. Multiple studies have reported a benefit of prophylactic inferior vena cava filter (IVCF) insertion in selected high-risk trauma patients. Often, these high-risk patients reside in the intensive care unit (ICU) and require mechanical ventilation, intracranial pressure monitoring, multiple intravenous infusions, and other invasive monitoring modalities. This puts these patients at risk for transport from the ICU. METHODS: We prospectively studied a series of consecutive patients undergoing bedside preinsertion contrast cavagram and IVCF insertion in the ICU. RESULTS: Thirty-two patients received IVCF. There were no failures to insert IVCF. One insertion-site hematoma occurred; however, there were no documented insertion-site deep venous thromboses. One patient death was unrelated to the IVCF, and one potential contrast-related acute renal failure occurred in an unstable patient who underwent IVCF insertion for a pulmonary embolus. CONCLUSION: Bedside IVCF insertion with a preinsertion cavagram is a percutaneous procedure that can be safely performed in the ICU. Bedside insertion of IVCF avoids the potential complications of transporting critically ill patients and may reduce costs.

Adolescent↗

Use of hydroxyurea in psoriasis.

Hydroxyurea is an effective treatment in chronic plaque psoriasis that is relatively simple to prescribe. Dose-related bone marrow toxicity is the principal side-effect of therapy although clinically significant complications are few, provided that blood counts are monitored carefully. In contrast with many other second-line agents, renal and liver disease do not necessarily preclude treatment, and there are few drug interactions likely to be of clinical relevance in dermatology. Recent studies on the use of hydroxyurea for sickle cell disease may provide more information on predicting the maximal tolerated dose and potential hazards of long-term therapy in nonmalignant disease and perhaps revive interest in the drug's use in dermatology.

Humans↗

Sodium-independent lysine uptake by the BeWo choriocarcinoma cell line.

Transport of L-lysine by a cultured placental trophoblast cell line was investigated by characterization of L-[3H]lysine uptake. In the mononuclear form of the BeWo clone b30 choriocarcinoma cell, at least two sodium-independent systems are present. Concentration dependence data were fitted by a two system model with Km values (+/- s.e.) of 2 +/- 0.7 and 94 +/- 31 microM and Vmax values (+/- s.e.) of 0.7 +/- 0.3 and 25 +/- 6.0 nM/mg DNA/min. A portion of sodium-independent uptake was inhibited by the sulphydryl modifying reagent N-ethylmaleimide (NEM). Following NEM treatment, the data were fitted by a single system with Km = 10 +/- 2 microM AND Vmax = 5.1 +/- 0.8 nM/mg DNA/min. In the absence of sodium, NEM-resistant uptake was sensitively inhibited by leucine whereas NEM-sensitive uptake was not inhibited by leucine. It is concluded that like placental basal membrane, the mononuclear BeWo cell possesses two sodium-independent L-lysine transport systems. The high-capacity, NEM-sensitive, leucine-insensitive system resembles the widespread system y+. The high-affinity, NEM-resistant, leucine-sensitive system resembles system b(0,+).

Biological Transport, Active↗

Effect of granulocyte macrophage-colony stimulating factor on Langerhans cells in normal and healthy atopic subjects.

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a multipotent cytokine produced by many cutaneous cell types including keratinocytes. Langerhans cells (LC) represent the major antigen-presenting cells in skin, and in vitro studies demonstrate that GM-CSF is of pivotal importance in LC. Healthy volunteers (n = 3 non-atopic, n = 3 with atopy) received recombinant human GM-CSF (0. 05 microg/mL) by intradermal injection for 3 days to the same site. Diluent was injected in a similar manner as control. Biopsies were taken 24 h after the final injection and examined immunohistochemically for LC and inflammatory cell markers. Compared with control sites, intradermal GM-CSF resulted in shortening of dendritic cell processes and redistribution of LC in the epidermis; numbers of CD1a + cells in the epidermis were significantly decreased (P < 0.005), while those in the dermis were significantly increased (P < 0.05) following intradermal GM-CSF when compared with controls. Double labelling studies on epidermal CD1a + cells indicated de novo expression of intercellular adhesion molecule (ICAM)-1 and increased expression of HLA-DR following GM-CSF (P < 0. 005, P < 0.005, respectively). Additional findings included a marked mixed inflammatory cell infiltrate in the dermis and increased expression of the endothelial cell adhesion molecules E-selectin and ICAM-1. These data indicate that in normal human skin, GM-CSF induces changes in the phenotype and distribution of CD1a + cells consistent with LC functional maturation and exit from the epidermis to the dermis. As these events are central to the initiation of cutaneous inflammation, GM-CSF may potentially play a critical role in the pathogenesis of inflammatory dermatoses.

Adolescent↗