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Biomedical subjects

C Smith

Publications and source records attributed to C Smith.

At least 19 recordsLinked to original sources
PubMed2006

Illuminating the interrelated immune and endocrine adaptations after multiple exposures to short immobilization stress by in vivo blocking of IL-6.

Intermittent psychological stress was induced in adult rats by 2 h/day of immobilization stress for 4 days, with or without blocking the function of IL-6 by using an anti-IL-6 antibody. Basal concentrations of serum corticosterone, IL-1beta, IL-6, and TNF-alpha were assessed 24 h after the last intervention, as were levels of glucocorticoid receptors (GR) and activities of glucocorticoid-inducible enzymes (tyrosine aminotransferase and glutamine synthetase) in muscle and liver. Whole blood cultures were used to assess both spontaneous and LPS-induced reactivity of peripheral blood mononuclear cells. Stress increased corticosterone concentration in a manner partially modulated by IL-6. Serum IL-1beta concentration was downregulated during stress when IL-6 was blocked (P < 0.01). LPS-induced IL-6 secretion by peripheral blood mononuclear cells in vitro correlated positively with serum IL-1beta concentration in antibody-treated groups, independently of stress (R = 0.70 in nonstressed and R = 0.78 in stressed rats; both P < 0.05), whereas serum corticosterone concentration correlated positively with LPS-induced secretion of IL-6 only in control rats (R = 0.66; P < 0.05). Reductions in liver GR levels indicated independent effects of stress (34.5%) and anti-IL-6 antibody (16.7%) and additive effects for both (62.5%). Similar results are reported for vastus muscle. Conversely, stress increased tyrosine aminotransferase and glutamine synthetase activities in muscle and liver with a significant (P < 0.05) effect of anti-IL-6 antibody only seen in stressed livers. In conclusion, IL-6 plays a role in maintaining circulating IL-1beta concentration after multiple exposures to stress, thus promoting a continued elevation of corticosterone release; in peripheral tissues, IL-6 antagonizes the effects of glucocorticoids, especially at the level of GR concentration.

Animals↗
PubMed2006

Comparison of linear accelerations from three measurement systems during "reach & grasp".

Given the increased use of accelerometers in movement analysis, validation of such inertial sensors against conventional 3D camera systems and performance comparisons of different sensors have become important topics in biomechanics. This paper evaluates and compares linear acceleration trajectories obtained from two different 3D accelerometers and derived from Vicon position data for an upper limb "reach & grasp" task. Overall, good correspondence between the three measurement systems was obtained. Sources of error are discussed.

Acceleration↗
PubMed2006

An activity-dependent increased role for L-type calcium channels in exocytosis is regulated by adrenergic signaling in chromaffin cells.

Chromaffin cells of the adrenal medulla represent a primary output of the sympathetic nervous system. Their electrical stimulation evokes the fusion of large dense core granules with the cell membrane and the exocytic release of multiple transmitter molecules into the circulation. There the transmitters contribute to the regulation of basic metabolism of the organism. Under physiological activity, granule fusion and transmitter release are limited by activity-dependent Ca(2+) influx, entering through multiple isoforms of voltage-gated calcium channels. In this study we utilize perforated-patch voltage-clamp recordings and depolarize mouse chromaffin cells in situ with action potential-like waveforms to mimic physiological firing. We measure calcium influx through specific isoforms and measure cell capacitance as an index of granule fusion. Combining these approaches we calculate specific stimulus-secretion efficiencies for L-type, N-type, P/Q-type and R-type calcium channels under varied physiological activity levels. Current influx through all channel subtypes exhibited an activity-dependent depression. As expected P/Q-type channels, while responsible for modest Ca(2+) influx, are tightly coupled to catecholamine secretion under all conditions. We further find that stimulation designed to match sympathetic input under the acute stress response recruits L-type channels to a state of enhanced stimulus-secretion efficiency. N- and R-type channels do not undergo activity-dependent recruitment and remain loosely coupled to the secretion. Thus, only L-type channels exhibit activity-dependent changes in their stimulus-secretion function under physiological stimulation. Lastly, we show that treatment with the beta-adrenergic agonist, isoproterenol, specifically blocks the increase in the stimulus-secretion function of L-type channels. Thus, increased cell firing specifically enhances stimulus-secretion coupling of L-type Ca(2+) channels in chromaffin cells in situ. This mechanism is regulated by an adrenergic signaling pathway.

Action Potentials↗
PubMed2006

Temperature as a variable in liquid chromatography: development and application of a model for the separation of model drugs using water as the eluent.

The use of high temperatures in liquid chromatography allows for the use of a purely aqueous mobile phase. At elevated temperatures water possesses many of the characteristics of organic solvents in terms of eluotropic strength, as well as having a lower viscosity. A model is developed, based on data obtained using a range of model drugs, which demonstrates the relationship between temperature, flow and pressure. Experimental data from different column types, at temperatures from 40 degrees C to 180 degrees C, is presented which matches well with the predicted data from the model.

Chromatography, High Pressure Liquid↗
PubMed2006

Widespread neonatal brain damage following calcium channel blockade.

An abundance of evidence exists that shows calcium channel blockade promotes injury in cultured neurons. However, few studies have addressed the in vivo toxicity of such agents. We now show that the L-type calcium channel antagonist nimodipine promotes widespread and robust injury throughout the neonatal rat brain, in an age-dependent manner. Using both isolated neuronal as well as brain slice approaches, we address mechanisms behind such injury. These expanded studies show a consistent pattern of injury using a variety of agents that lower intracellular calcium. Collectively, these observations indicate that postnatal brain development represents a transitional period for still developing neurons, from being highly sensitive to reductions in intracellular calcium to being less vulnerable to such changes. These observations directly relate to current therapeutic strategies targeting neonatal brain injury.

Animals↗
PubMed2006

Homoeopathic Oscillococcinum for preventing and treating influenza and influenza-like syndromes.

BACKGROUND: Influenza is a highly infectious viral disease that is particularly common in the winter months. Oscillococcinum is a patented, commercially available homoeopathic medicine. The rationale for its use in influenza comes from the homoeopathic principle of 'let like be cured by like'. This medicine is manufactured from wild duck heart and liver, which are said to be reservoirs for influenza viruses. OBJECTIVES: To determine whether homoeopathic Oscillococcinum or similar medicines are more effective than placebo in the prevention and treatment of influenza and influenza-like syndromes. SEARCH STRATEGY: We updated the electronic searches on the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006); MEDLINE (January 1966 to February 2006) and EMBASE (1980 to February 2006). The manufacturers of Oscillococcinum were contacted for information. SELECTION CRITERIA: Placebo-controlled trials of Oscillococcinum or homeopathically-prepared influenza virus, influenza vaccine or avian liver in the prevention and treatment of influenza and influenza-like syndromes. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed methodological quality independently. MAIN RESULTS: Seven studies were included in the review, three prevention trials (number of participants (n) = 2265) and four treatment trials (n = 1194). Only two studies reported sufficient information to complete data extraction fully. There was no evidence that homoeopathic treatment can prevent influenza-like syndrome (relative risk (RR) 0.64, 95% confidence interval (CI) 0.28 to 1.43). Oscillococcinum treatment reduced the length of influenza illness by 0.28 days (95% CI 0.50 to 0.06). Oscillococcinum also increased the chances that a patient considered treatment to be effective (RR 1.08; 95% CI 1.17 to 1.00). AUTHORS' CONCLUSIONS: Though promising, the data were not strong enough to make a general recommendation to use Oscillococcinum for first-line treatment of influenza and influenza-like syndromes. Further research is warranted but the required sample sizes are large. Current evidence does not support a preventative effect of Oscillococcinum-like homeopathic medicines in influenza and influenza-like syndromes.

Homeopathy↗
PubMed2006

MK801-induced caspase-3 in the postnatal brain: inverse relationship with calcium binding proteins.

Age-dependent, neuronal apoptosis following N-methyl-D-aspartate receptor blockade has been linked to loss of calcium. To further explore this relationship, we examined expression of activated caspase-3, as well as the calcium binding proteins, calbindin-D 28K, calretinin and parvalbumin, following injection of vehicle or the N-methyl-D-aspartate receptor blocker, MK801, in postnatal day 7 or 21 rats. At postnatal day 7, MK801-induced activated caspase-3 expression was most frequently found in mutually exclusive cell populations to those expressing any of the three calcium binding proteins. For example, in the somatosensory cortex, most immunoreactivity for activated caspase-3 was found in layers IV/V, layered between areas of high calbindin or calretinin expression. Further, in the caudate putamen, activated caspase-3 rarely invaded zones of intense calbindin immunoreactivity. Suggesting expression patterns of these proteins were inversely related, these same brain regions no longer displayed MK801-induced activated caspase-3 at postnatal day 21, but instead robustly expressed calcium binding proteins. This later surge in expression was especially true for parvalbumin in regions such as the somatosensory and retrosplenial cortex, as well as the subicular complex. Calbindin-D 28K was also found to increase in the same regions though not as impressively as parvalbumin. Thus, developmental regulation of calcium binding protein expression may be a critical factor in age-dependent sensitivity to agents that disrupt calcium homeostasis in maturing neurons, providing a possible mechanistic explanation for age-dependent MK801 toxicity.

Age Factors↗
PubMed2006

Human telomerase reverse transcriptase protects hematopoietic progenitor TF-1 cells from death and quiescence induced by cytokine withdrawal.

Telomerase is a complex ribonucleoprotein enzyme that exhibits elevated activity in the majority of cases of human leukemia. We have previously shown that retroviral expression of the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), in human cord blood CD34+ cells leads to an enhanced survival of mature hematopoietic cells. The mechanism for this pro-survival effect is not known. Here, we show that telomerase may play a role in leukemogenesis as a survival factor, independent of its role in maintaining telomere length. Retroviral expression of hTERT in the cytokine-dependent, human hematopoietic progenitor cell line, TF-1, resulted in the survival of cells following the withdrawal of cytokine, with protection from apoptosis, but did not promote unlimited replicative potential. This hTERT-mediated effect on cell survival does not involve Bcl-2 family members, results in accumulation of cells in G1 and appears to operate via autocrine expression of IL-3 and activation of the p53/p21 pathway. Survival in the absence of cytokine stimulation was also observed following retroviral expression of hTERT in normal cord blood CD34+ cells. This study demonstrates a novel pro-survival role for hTERT and may have important implications for the role of hTERT in the pathogenesis of leukemia and drug resistance.

Apoptosis↗
PubMed2006

Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK.

Between 1970 and 2003, seven cases of human dura mater-associated Creutzfeldt-Jakob disease (CJD) were identified in the UK. Furthermore, we identified a case of CJD in a porcine dura graft recipient. The mean incubation period of the human dura mater cases was 93 (range 45-177) months. The clinico-pathological features of the cases are described and compared with cases previously reported in the world literature.

Adult↗
PubMed2006

Measuring the quality of continuous epidural block for abdominal surgery.

BACKGROUND: In view of the wide variation in pain experience between patients, a clinical standard -- the time from the end of surgery to the first experience of pain -- was applied to 1359 consecutive patients in order to investigate whether the initial quality of epidural block has an effect on the overall quality of postoperative pain relief. METHODS: Clinical data were recorded in 58,118 out of 72,412 h in 1359 patients, and transferred to a database. Data collected included pain scores on a four-point verbal rating scale; nausea and vomiting; motor block; sedation scores; systolic blood pressure <100 and <90 mm Hg; ventilatory frequency <10 and <8 bpm; and hourly epidural infusion rate. RESULTS: As the time to first experience of pain increased from nil to >24 hours, the time from the first to last experience of pain shortened from 34 (19-50) h to 3 (1-12) h (p<0.001) and the proportion of patients receiving an epidural bolus decreased from 53 to 8% (p<0.001). Increases in the initial pain free time increased the proportion of patients with systolic BP<100 mmHg from 59 to 77%, (p<0.001) and increased the proportion of patients with respiratory rate <10 bpm from 13 to 26%, (p<0.001). CONCLUSION: Extending pain relief for more than 12 h beyond the end of abdominal surgery significantly improves the overall quality of postoperative pain relief, but is associated with an increase in side-effects.

Abdomen↗
PubMed2006

In situ determination of salinity by PGNAA.

Salinity is a very important environmental issue all around the world. In many cases salinity was produced from human activities like farming and mining. Different soluble salts contribute to salinity, however, NaCl is the most common salt producing salinity. This work deals with the application of the prompt gamma neutron activation analysis (PGNAA) technique for in situ determination of salinity. The technique is based on the measurement of chlorine, a component of the common salt, by PGNAA.

Journal Article↗
PubMed2006

A randomised controlled trial of the use of a tourniquet to reduce blood loss during transtibial amputation for peripheral arterial disease.

OBJECTIVES: To examine the effects of an exsanguination tourniquet on blood loss during transtibial amputation in patients with peripheral arterial disease (PAD). DESIGN: Prospective randomised blinded controlled trial. MATERIALS AND METHODS: Sixty-four patients undergoing transtibial amputation for non-reconstructible PAD were randomised to either tourniquet or no tourniquet (control). Blood loss (primary outcome), fall in haemoglobin, transfusion requirements, wound healing, breakdown and revision (secondary outcomes) were also recorded. RESULTS: Twenty-five patients in the tourniquet and 29 in the control group conformed to the trial protocol and completed the follow up. Intra-operative blood loss (median and IQR) was significantly greater in the control group compared to the tourniquet group (550 ml (255-1050) vs 255 ml (150-572.5), respectively, p=0.014, Mann-Whitney). There was a significantly greater drop in haemoglobin concentration (median and IQR) in the control compared to the tourniquet group (1.8 g/dl (0-1.2) vs 1.0 g/dl (0.6-2.4), p=0.035, t-test). Transfusion requirements were lower in the tourniquet group (p=0.05, Mann-Whitney). The rate of wound healing, breakdown and revision were similar in the tourniquet and control groups, respectively (59 vs 57%, 0 vs 9%, 14 vs 9%, p=NS). CONCLUSIONS: The use of a tourniquet during transtibial amputation for severe PAD reduces blood loss and need for blood transfusion.

Aged↗
PubMed2006

Minimally invasive technique for ligation and stripping of the small saphenous vein guided by intra-operative duplex ultrasound.

BACKGROUND: Small saphenous vein (SSV) disconnection and removal are challenging and considered by some authors to have too high a morbidity and failure rate to justify their routine use. Our audited results are at variance with these views. METHODS: We describe a reliable, ultrasound guided, minimally invasive technique for ligation and stripping of the SSV with an incision usually <1 cm. From our total series, 50 random patients attended for ultrasound review. The sapheno-popliteal junction (SPJ), strip track and signs of recurrence were assessed and recorded. RESULTS: Since 1999, 627 patients (679 limbs) have undergone surgery for ultrasound proven SSV reflux. Fifty-two limbs (50 patients) were ultrasound assessed post-operatively. Fifty-one had flush ligation of the SPJ with one showing a 'stump' <1 cm. All showed successful SSV removal. Three limbs had minor strip track revascularisation but none had obvious clinical recurrence. Of the whole series, 11/627 (1.8%) developed proven deep vein thrombosis (DVT). There were six superficial wound infections and one strip track abscess. Sural nerve neurapraxia occurred in 13/627 (2.1%); one showing no sign of recovery at four weeks post-operatively. CONCLUSIONS: Ultrasound guided SSV is a safe, minimally invasive technique with high success and low recurrence and complication rates

Female↗
PubMed2006

An unusual progression of benign thoracic spinal cord teratoma in pregnancy: a hormonally-mediated pathway?

Intradural spinal cord teratoma is a very rare tumour that can be associated with dysraphism. The relationship of this lesion to pregnancy is unknown and its occurrence during pregnancy in the thoracic spine has not been previously reported. We report a 19-year-old pregnant woman with spinal dysraphism, who presented with a new onset thoracic myelopathy. The MRI scan showed an intradural, extramedullary lesion with solid and cystic component in the thoracic spine at the level of T5-T6. A thoracic laminectomy and excision of this lesion was followed by significant improvement of her lower limb function. Histopathology confirmed a benign mature teratoma. The rapid progression of this lesion during pregnancy suggests a hormonal mediated pathway for the tumour growth. Further analysis from the resected specimen confirmed that the tumour was oestrogen and progesterone receptors positive.

Adult↗
PubMed2006

Leukocyte count as a predictor of death during remission induction in acute myeloid leukemia.

Acute myeloid leukemia (AML) presenting with a high leukocyte count has been associated with an increase in induction mortality and poor results in a number of other survival measures. However, the level at which an elevated leukocyte count has prognostic significance in AML remains unclear. In this report on a series of 375 adult (non-M3) AML patients undergoing induction chemotherapy at a single institution, leukocyte count analyzed as a continuous variable is shown to be a better predictor of induction death (ID) and overall survival (OS) than a leukocyte count of > or = 100 x 10(9)/L, a value characteristically associated with "hyperleukocytosis" (HL). In this patient cohort, a presenting leukocyte count of > or = 30 x 10(9)/L had high sensitivity and specificity for predicting ID, and both performance status (PS) and leukocyte count more accurately predicted for ID than age. Considering these parameters in newly-diagnosed AML patients may facilitate the development of strategies for reducing induction mortality.

Adolescent↗
PubMed2006

The costs and benefits in an unusual symbiosis: experimental evidence that bitterling fish (Rhodeus sericeus) are parasites of unionid mussels in Europe.

Interspecific symbiotic relationships involve a complex network of interactions, and understanding their outcome requires quantification of the costs and benefits to both partners. We experimentally investigated the costs and benefits in the relationship between European bitterling fish (Rhodeus sericeus) and freshwater mussels that are used by R. sericeus for oviposition. This relationship has hitherto been thought mutualistic, on the premise that R. sericeus use mussels as foster parents of their embryos while mussels use R. sericeus as hosts for their larvae. We demonstrate that R. sericeus is a parasite of European mussels, because it (i) avoids the cost of infection by mussel larvae and (ii) imposes a direct cost on mussels. Our experiments also indicate a potential coevolutionary arms race between bitterling fishes and their mussel hosts; the outcome of this relationship may differ between Asia, the centre of distribution of bitterling fishes, and Europe where they have recently invaded.

Animals↗
PubMed2006

Cervical screening in HIV-positive women: characteristics of those who default and attitudes towards screening.

OBJECTIVES: To determine the characteristics of HIV-positive women who undergo cervical screening and to identify negative attitudes and experiences of these women to screening and the factors associated with these. METHODS: We compared the Royal Free Cohort data from 59 newly diagnosed HIV-infected women, 31 of whom did and 28 of whom did not attend for cervical screening in 2001, and from 227 women under active cervical screening follow-up (at least one cervical screen since June 2001) and 88 HIV-infected women lost to follow-up (not screened since January 2001). Attitudes to screening were investigated with the aid of a questionnaire given to all women attending clinic who had had a previous colposcopy. RESULTS: Of the 59 newly HIV diagnosed women, 31 (53%) underwent cervical screening. These 31 women were more likely to be heterosexual (100 vs 89%, P=0.05), to have lower median viral loads (< 50 vs 3210 HIV-1 RNA copies/mL) and to be receiving antiretrovirals (ARVs) (74 vs 54%, P=0.1) than those not screened. Of the 315 women who had at least one screen, 72% returned for further follow-up. There were no differences in age or ethnicity between these groups. Those under active follow-up had a higher CD4 count (P=0.04) and lower viral load (P=0.0001) at their last visit. They were also more likely to be on highly active antiretroviral therapy (HAART) (68 vs 52%, P=0.006). A total of 78 of 104 questionnaires (75%) were returned. Women participating in the questionnaire study were mainly of back ethnicity (68%), did not speak English as their first language (59%) and were taking ARVs (76%). Most agreed that regular smears and colposcopy were valuable. Women of white ethnicity, and those speaking English as a first language, were more likely to dislike colposcopy compared with those of nonwhite ethnicity (87 vs 25%, respectively, P=0.0007) and not speaking English as a first language (74 vs 26%, respectively, P=0.002). Those of white ethnicity were more likely to find smears and colposcopy painful (60 and 73%) compared with those of black ethnicity (46 and 51%, P=0.47 and 0.28, respectively). CONCLUSIONS: Our results suggest that women on HAART with better disease control, older women, and those of black African ethnicity are more likely to take up cervical screening. Cervical screening experience varies by ethnicity and language.

Adult↗