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D Smith

Publications and source records attributed to D Smith.

At least 163 records · Page 9Linked to original sources
PubMed2001

A parametric study of freezing injury in ELT-3 uterine leiomyoma tumour cells.

Cellular level freeze injury was investigated after controlled freezing of an Eker rat uterine fibroid cell line in both the presence and absence of oestradiol. The connection between thermal history and cell injury in single ELT-3 cells in suspension (without oestradiol) was studied through a two-level, four-parameter (2(4)) experiment with membrane dye exclusion as the end-point. The four parameters considered were cooling rate (CR), end temperature (ET), hold time (HT) and thawing rate (TR). A high and low value of each parameter was selected as follows: CR, 5-25 degrees C/min; ET, -20 to -30 degrees C; HT, 0-5 min; TR 20-200 degrees C/min. The greatest parameter effect on freeze injury in this range was ET followed by HT, then TR and finally CR. In addition, significant parameter interactions and curvature were found. Additional CR results outside the original parameter range showed a reduction in survival at both 1 and 50 degrees C/min suggestive of an inverted U-shaped survival curve. These results show that this tumour system is susceptible to cryoinjury, particularly at temperatures below -30 degrees C with HT of >5 min and slow thawing. In addition, the presence of oestradiol was found to increase the susceptibility of these cells to cryoinjury.

Animals↗
PubMed2001

Abnormal fetal growth is not associated with altered chorionic villous expression of vascular endothelial growth factor mRNA.

Altered placental and circulating levels of vascular endothelial growth factor (VEGF) and its receptor (flt-1) may be associated with pre-eclampsia and intrauterine growth restriction (IUGR). The aim of this study was to determine whether chorionic villous VEGF or flt-1 mRNA are altered at early gestation in pregnancies subsequently found to be complicated by abnormal fetal growth. Quantitative reverse transcription-polymerase chain reaction was performed on chorionic villous samples for VEGF and flt-1 using an internal RNA standard. Using the individualized birthweight ratio (IBR), the subjects (n = 51) were divided into three groups; IUGR (IBR <10th centile, n = 6), normal (IBR 10th-90th centiles, n = 41) and macrosomic (IBR >90th centile, n = 4). There was no correlation between the mRNA expression of VEGF(121) or VEGF(165) and gestational age of the normal controls. There was also no difference in the expression of either of the VEGF isoforms between the IUGR or macrosomic groups and the normal controls. Expression of flt-1 was below the detection limit of the assay. In conclusion, we have found that altered chorionic villous expression of VEGF is not associated with the initial stages of development of IUGR or macrosomia.

Actins↗
PubMed2001

A new 'online' method to measure increased exhaled isoprene in end-stage renal failure.

BACKGROUND: Isoprene is the most abundant hydrocarbon present in breath, and recent reports indicate that breath concentrations increase following haemodialysis. The purpose of this study was to establish whether selected ion flow tube mass spectrometry (SIFT-MS), a newly established technique in breath analysis, may be used to quantify breath isoprene in haemodialysis patients in the clinical setting. SIFT-MS is compared and contrasted with the established gas chromatography mass spectrometric technique for this purpose. METHODS: Three consecutive exhalations from 19 haemodialysis patients (12 males, seven females) undergoing a morning dialysis shift were analysed just prior to commencing treatment. Within 5 min of completing their usual dialysis regimen, using polysulphone membranes, the breath of each patient was analysed again. Additional contemporary samples were obtained from 17 normal controls. Breath isoprene was quantified using SIFT-MS, a method previously validated quantitatively using neat isoprene. RESULTS: Successful measurements of breath isoprene were obtained for each subject within 2 min, with minimum disruption to a busy dialysis environment. The coefficient of variation of triplicate measurements of breath isoprene was <10%. Prior to dialysis, the mean (+/-SD) breath isoprene concentration (138+/-63 parts per billion (ppb)) was significantly greater than for normal controls (89+/-36 ppb; P=0.016). Immediately following treatment, breath isoprene increased significantly to 184+/-95 ppb (P=0.023). CONCLUSIONS: SIFT-MS permits the accurate and rapid measurement of breath isoprene in haemodialysis patients in the clinical setting. The previously reported increase in breath isoprene following dialysis treatment is confirmed. SIFT-MS is the ideal analytical tool to investigate this phenomenon further.

Acute Kidney Injury↗
PubMed2001

Effect of two drafting modalities in cycling on running performance.

PURPOSE: The purposes of this study were first to compare the physiological responses during a triathlon where cycling was performed alternatively with another cyclist (alternate draft triathlon, ADT) or continuously behind him (continuous draft triathlon, CDT), and second to study the incidence of these two drafting modalities in cycling on the subsequent running performance done during a simulated triathlon. METHODS: Ten male triathletes of national level performed a sprint distance triathlon (0.75-km swim, 20-km bike, 5-km run) on two different sessions, one where the triathlete alternatively rode in front or at the back of another cyclist and rotating every 500 m, the other where the triathlete drafted continuously a professional cyclist whose task was to reproduce all split times recorded during the alternate situation. Oxygen uptake (VO2), expiratory flow (VE), heart rate (HR) were recorded during the entire bike and run sections and blood lactate concentrations ([La-]b) were analyzed at the end of each event composing the triathlon. RESULTS: The results showed that expiratory flow, oxygen uptake, heart rate and blood lactate concentrations were significantly lower in CDT on the bike compared with drafting in alternation (148.1 vs. 167.2 L.min-1, 49.9 vs. 59.8 mL.min-1.kg-1, 154.7 vs. 173.1 beats.min-1, 3.5 vs. 6.3 mmol.L-1, respectively). The results also revealed that running after biking in CDT (for similar cycling speeds) significantly improved the subsequent running speed compared to ADT (17.87 vs. 17.15 km.h-1). Furthermore, VE, VO2, HR, and [La-]b were significantly higher during CDT run compared with ADT run (175.6 vs. 170.4 L.min-1, 69.7 vs. 66.8 mL.min-1.kg-1, 182.6 vs. 177.3 beats.min-1, 9.6 vs. 7.5 mmol.L-1, respectively). CONCLUSIONS: These results showed that drafting continuously behind a lead cyclist allows triathletes to save a significant amount of energy during the bike leg of a sprint triathlon and creates the conditions for an improved running performance compared with a situation where cycling is performed alternating the lead with another cyclist.

Adult↗
PubMed2001

The Camino intracranial pressure sensor: is it optimal technology? An internal audit with a review of current intracranial pressure monitoring technologies.

OBJECTIVE: To audit the reliability of the Camino intracranial pressure (ICP) sensor (Camino Laboratories, San Diego, CA) in our clinical practice as part of a continuing quality assurance program, and to assess its relative usefulness as compared with currently available ICP monitoring technologies that we reviewed. DESIGN: Prospective audit of ICP device reliability and function in 50 patients with head injuries. METHODS: Zero drift was recorded immediately after the ICP device was removed from the patient. Dynamic frequency response bench testing of each functioning catheter from 0 to 30 Hz and static calibration testing from 0 to 100 mmHg during environmental temperature variation from 22 to 40 degrees C were carried out. RESULTS: Zero drift (range, -13 to 22 mmHg; median, -1 mmHg) was recorded immediately after the devices were removed from patients. Seventeen (50%) of the devices tested for zero drift had absolute drifts of at least 3 mmHg. There was no correlation between recorded zero drift and duration of monitoring (r = 0.154, P = 0.207). Five sensors (10% of those tested) failed during patient monitoring and were replaced. Static and dynamic calibration tests of the functioning sensors were within the manufacturer's specifications. However, the sensitivity of the devices to environmental temperature remains a problem. CONCLUSION: The Camino ICP sensor remains one of the most popular ICP monitoring devices for use in patients with traumatic brain injuries. However, our recent in-house assessment demonstrated the robustness of the device to be less than adequate during routine practice. In this study, more than 50% exhibited zero drift greater than 3 mmHg, which is unacceptable in a catheter tip ICP monitoring device in which zero drift and calibration cannot be checked in vivo. A review of the literature revealed that other available ICP monitoring devices may prove to be more reliable and thus more appropriate for routine clinical measurement of ICP.

Equipment Design↗
PubMed2001

Calcification properties of saline-filled breast implants.

Three patients requested explantation of their saline-filled breast implants. Bilateral calcification had occurred in all six implants. Four of the implants were manufactured by McGhan Corporation (Santa Barbara, Calif.), and two, by the Simaplast Company (Toulon, France). All implants had been inserted in the subglandular plane and had been in place for 7 to 23 years. At the time of explantation, patients were 32, 34, and 44 years old. Calcification on the surface of the implants and capsules was analyzed. Implant surface calcification was clinically evident on all six implants, appearing as ivory-colored, tenaciously adherent deposits, only on the anterior surface of the implant. Capsular calcification, which was observed only microscopically, was characterized by poorly organized, irregularly shaped, calcified agglomerates; this calcification also occurred only on the anterior surface of the capsule, adjacent to the area of calcification on the implant. Ultrastructural analysis of scrapings from the implant surface showed large, electron-dense aggregates of crystals, with individual crystals measuring approximately 40 x 10 x 10 nm. In contrast, capsular calcification was characterized by two patterns of deposition, spherulitic aggregates of needle-shaped crystals and areas of metaplastic bone. The individual crystals were approximately 40 x 10 x 10 nm. Energy-dispersive x-ray spectroscopy of specimens from the areas of calcification on the implant and capsule surfaces demonstrated calcium and phosphorus. Electron diffraction of crystals from the implant and capsule surfaces demonstrated the D-spacings characteristic of calcium apatite. There were many differences between the calcification properties of these six saline implants and those of silicone gel implants. For example, mineralization has not been observed on the surface of gel implants, but in these saline implants it occurred primarily on the implant surface. Also, capsular calcification has been observed clinically in gel implants across the surface of the capsule (except at the site of attachment of a Dacron patch), but in this study it was observed only microscopically and was located on the anterior surface of the capsule, adjacent to the area of calcification on the implant. In addition, crystals 100 times larger than those observed on the six saline implant capsules have been observed on the surface of gel implant capsules. A model is presented to explain the mechanism of calcification associated with breast implants and to explain the observed differences between saline-filled and gel-filled implants.

Adult↗
PubMed2001

Additional educational needs in children born to mothers with epilepsy.

OBJECTIVES: To examine the relative risks of additional educational needs (AENs) in children exposed to antiepileptic drug (AED) monotherapy and polytherapy regimes in utero. METHODS: A retrospective survey of women between the ages of 16 to 40 registered at the Mersey Regional Epilepsy Clinic, who received a postal questionnaire concerning their experience of pregnancy and the subsequent schooling of live-born children. RESULTS: 721 (57%) women of the 1267 approached returned an adequately completed questionnaire; 330 (46%) had given birth to at least one live-born child. Information was collected on 594 children, 400 of whom were of school age (4-18). 150 (37.5%) had been exposed to monotherapy in utero, 74 (18.5%) were exposed to polytherapy, and 176 were not exposed to any AEDs. The odds ratio of AENs for all children exposed to AEDs in utero compared with those unexposed was 1.49 (95% confidence interval (95% CI) 0.83 -2.67). Odds ratios for AENs for each therapy subgroup compared with those unexposed were also calculated for all children. Those exposed to valproate monotherapy had an odds ratio of 3.4 (95% CI 1.63-7.10) by contrast with an odds ratio of 0.26 (95% CI 0.06- 1.15) for carbamazepine. Polytherapy including valproate had similarly high odds ratios for AENs compared with those unexposed of 2.51 ( 95% CI 1.04-6.07) versus the odds ratio of 1.51 ( 95% CI 0.56-4.07) for polytherapy excluding valproate. CONCLUSIONS: Although the findings should be treated with caution, they suggest that monotherapy or polytherapy with valproate during pregnancy carries particular risks for the development of children exposed in utero.

Adolescent↗
PubMed2001

Postprandial dyslipidemia in men with visceral obesity: an effect of reduced LDL receptor expression?

Postprandial lipemia after an oral fat challenge was studied in middle-aged men with visceral obesity. The two groups had similar plasma cholesterol levels, but obese subjects had higher levels of plasma triglyceride and reduced amounts of high-density cholesterol. Fasting plasma insulin was fourfold greater in obese subjects because of concomitant insulin resistance, with a calculated HOMA score of 3.1 +/- 0.6 vs. 0.8 +/- 0.2, respectively. Plasma apolipoprotein B(48) (apoB(48)) and retinyl palmitate (RP) after an oral fat challenge were used to monitor chylomicron metabolism. Compared with lean subjects, the fasting concentration of apoB(48) was more than twofold greater in obese individuals, suggestive of an accumulation of posthydrolyzed particles. After the oral lipid load, the incremental areas under the apoB(48) and RP curves (IAUC) were both significantly greater in obese subjects (apoB(48): 97 +/- 17 vs. 44 +/- 12 microg.ml(-1). h; RP: 3,120 +/- 511 vs. 1,308 +/- 177 U. ml(-1). h, respectively). A delay in the conversion of chylomicrons to remnants probably contributed to postprandial dyslipidemia in viscerally obese subjects. The triglyceride IAUC was 68% greater in obese subjects (4.7 +/- 0.6 vs. 2.8 +/- 0.8 mM. h, P < 0.06). Moreover, peak postprandial triglyceride was delayed by approximately 2 h in obese subjects. The reduction in triglyceride lipolysis in vivo did not appear to reflect changes in hydrolytic enzyme activities. Postheparin plasma lipase rates were found to be similar for lean and obese subjects. In this study, low-density lipoprotein (LDL) receptor expression on monunuclear cells was used as a surrogate marker of hepatic activity. We found that, in obese subjects, the binding of LDL was reduced by one-half compared with lean controls (70.9 +/- 15.07 vs. 38.9 +/- 4.6 ng LDL bound/microg cell protein, P = 0.02). Because the LDL receptor is involved in the removal of proatherogenic chylomicron remnants, we suggest that the hepatic clearance of these particles might be compromised in insulin-resistant obese subjects. Premature and accelerated atherogenesis in viscerally obese, insulin-resistant subjects may in part reflect delayed clearance of postprandial lipoprotein remnants.

Apolipoprotein B-48↗
PubMed2001

CTP:phosphocholine cytidylyltransferase inhibition by ceramide via PKC-alpha, p38 MAPK, cPLA2, and 5-lipoxygenase.

In a companion paper (Vivekananda J, Smith D, and King RJ. Am J Physiol Lung Cell Mol Physiol 281: L98-L107, 2001), we demonstrated that tumor necrosis factor (TNF)-alpha inhibited the activity of CTP:phosphocholine cytidylyltransferase (CT), the rate-limiting enzyme in the de novo synthesis of phosphatidylcholine (PC), and that its actions were likely exerted through a metabolite of sphingomyelin. In this paper, we explore the signaling pathway employed by TNF-alpha using C2 ceramide as a cell-penetrating sphingolipid representative of the metabolites induced by TNF-alpha. We found that in H441 cells, as reported in other cell types, cytosolic phospholipase A2 (cPLA2) is activated by TNF-alpha. We also observed that the inhibiting action of C2 ceramide on CT requires protein kinase C-alpha, p38 mitogen-activated protein kinase, and cPLA2. The actions of C2 ceramide on CT activity can be duplicated by adding 2 microM lysoPC to these cells. Furthermore, we found that the effects of C2 ceramide are dependent on 5-lipoxygenase but that cyclooxygenase II is unimportant. We hypothesize that CT activity is inhibited by the lysoPC generated as a consequence of the activation of cPLA2 by protein kinase C-alpha and p38 mitogen-activated protein kinase. The other product of the activation of cPLA2, arachidonic acid, is a substrate for the synthesis of leukotrienes, which raise intracellular Ca2+ levels and complete the activation of cPLA2.

Arachidonate 5-Lipoxygenase↗
PubMed2001

Sphingomyelin metabolites inhibit sphingomyelin synthase and CTP:phosphocholine cytidylyltransferase.

Tissue injury in inflammation involves the release of several cytokines that activate sphingomyelinases and generate ceramide. In the lung, the impaired metabolism of surfactant phosphatidylcholine (PC) accompanies this acute and chronic injury. These effects are long-lived and extend beyond the time frame over which tumor necrosis factor (TNF)-alpha and interleukin-1beta are elevated. In this paper, we demonstrate that in H441 lung cells these two processes, cytokine-induced metabolism of sphingomyelin and the inhibition of PC metabolism, are directly interrelated. First, metabolites of sphingomyelin hydrolysis themselves inhibit key enzymes necessary for restoring homeostasis between sphingomyelin and its metabolites. Ceramide stimulates sphingomyelinases as effectively as TNF-alpha, thereby amplifying the sphingomyelinase activation, and TNF-alpha, ceramide, and sphingosine all inhibit PC:ceramide phosphocholine transferase (sphingomyelin synthase), the enzyme that restores homeostasis between sphingomyelin and ceramide pools. Second, ceramide inhibits PC synthesis, probably because of its effects on CTP:phosphocholine cytidylyltransferase, the rate-limiting enzymatic step in de novo PC synthesis. The data presented here suggest that TNF-alpha may be an inhibitor of phospholipid metabolism in inflammatory tissue injury. These actions may be amplified because of the ability of metabolites of sphingomyelin to inhibit the pathways that should restore the normal ceramide-sphingomyelin homeostasis.

Ceramides↗
PubMed2001

A phase I trial of a 5-day schedule of intravenous topotecan and etoposide in previously untreated patients with small-cell lung cancer.

A phase I dose-escalation study was undertaken to determine the maximum tolerated dose of the intravenous combination of topotecan and etoposide in previously untreated patients with small-cell lung cancer. Nineteen patients were treated with 30-min infusions of topotecan (0.5 mg/m(2)/day for cohort 1; 0.75 mg/m(2)/day for cohort 2) followed by 1-hour infusions of a fixed daily dose of etoposide (60 mg/m(2)/day) for 5 consecutive days every 3 weeks. Patient cohort 1 (n = 7) received a total of 41 courses of chemotherapy. Grade 4 neutropenia occurred after 17% of the courses of therapy, and there was 1 episode of dose-limiting toxicity in this patient cohort. In patient cohort 2 (n = 12), a total of 64 courses of chemotherapy were administered. Grade 3 or 4 neutropenia occurred following 41 and 37% of the courses of therapy, respectively. Grade 3 thrombocytopenia occurred following 19% of the courses of therapy, and there were 3 episodes of dose-limiting toxicity in this patient cohort. There were no toxic deaths, and all nonhematologic toxicity (except hair loss) was </= grade 2. No further dose escalation was performed because of the degree of myelosuppression seen in patient cohort 2. All 19 patients were evaluable for response. Eighteen (95%) patients responded (14 partial responses and 4 complete responses) and the median survival was 10 months. This 5-day schedule of intravenous topotecan and etoposide administered sequentially on the same day is well tolerated, and the preliminary response rates were high in patients with previously untreated small-cell lung cancer.

Aged↗
PubMed2001

Expression of alpha-, beta-, and gamma-hENaC mRNA in the human nasal, bronchial, and distal lung epithelium.

The amount of fluid covering the epithelium of the airways and alveolar space is modulated by active transport of Na+ from the lumen through the apical membrane Na+ permeant ion channels towards the interstitial space. We have measured the subunit expression of the amiloride-sensitive human Na+ channel (hENaC) by concomitant assessment of alpha-, beta-, and gamma-hENaC mRNA in the nasal, bronchial, and peripheral lung epithelia of adult patients undergoing lobectomy secondary to lung cancer. The study employed quantitative competitive reverse-transcriptase-polymerase chain reaction and qualitative in situ hybridization techniques. The hENaC mRNA content of each sample was normalized to the amount of epithelial cell-specific cytokeratin 18 (CK18) mRNA. Nasal epithelium contained significantly more (p < 0.05) alpha-hENaC mRNA (18 +/- 5 SD amol/fmol CK18), than bronchus (8 +/- 2 SD amol/fmol) and peripheral lung (9 +/- 2 SD amol/fmol). The ratio of gamma-hENaC/alpha-hENaC mRNA concentration was lowest in the nasal area, and it increased significantly towards the distal lung regions. The change in beta-hENaC mRNA was less profound. In situ hybridization studies of bronchial and peripheral lung sections selectively revealed expression of alpha-hENaC mRNA in superficial epithelium and submucosal glands of large airways, in bronchiolar epithelium, and in alveolar cells. We conclude that the relative expression of the hENaC subunit genes changes from the proximal to distal regions of the human respiratory tract.

Aged↗
PubMed2001

Introducing clinical supervision. The pitfalls and problems.

In July 1999 I published an article in the BJPN entitled 'Introducing Clinical Supervision into the Perioperative Environment' (Smith 1999). I described what I believed to be the successful implementation of clinical supervision to the trained theatre staff. I discussed the perceived benefits of improved communication, assistance with learning, professional development and reflective practice, provision of emotional support, evidence for PREPP, clinical effectiveness and governance, and improvement practice and policy making. Results from many other authors and professional bodies also proclaim both the need for, and the benefits, of clinical supervision for nurses.

Attitude of Health Personnel↗
PubMed2001

The selection of marmoset monkeys (Callithrix jacchus) in pharmaceutical toxicology.

Prior to controlled clinical trials in human volunteers or patients it is required that novel pharmaceuticals are evaluated for pre-clinical safety in a rodent and a non-rodent ('second') species. In most cases the rodent species used has been the rat and the second species has been the dog or macaque (usually cynomolgus or rhesus) monkey. However, there is an increasing trend within the United Kingdom (UK) pharmaceutical industry to use the common marmoset (Callithrix jacchus) for pre-clinical toxicology programmes. This paper examines the practicality of using the common marmoset (henceforth referred to as 'the marmoset') in toxicological testing and reviews metabolic and pharmacodynamic similarities between this species and humans. It then discusses some of the advantages and disadvantages of the use of this species when compared with two other alternatives to the dog and macaque, namely the ferret and minipig. In particular, the marmoset has clear advantages over the macaque in terms of animal welfare and practicality. There is regulatory acceptance of this species for Investigational New Drug (IND), Clinical Trial Exemption (CTX), New Drug Application (NDA) and Marketing Authorization Application (MAA) registrations. Whilst the dog is likely to be maintained as the primary non-rodent species in toxicology, the marmoset has been, and will likely continue to be, adopted as an additional non-rodent species in pre-clinical toxicology programmes where appropriate.

Animal Welfare↗
PubMed2001

A cross-national comparison of the impact of family migration on women's employment status.

In this paper we consider the effects of family migration on women's employment status, using census microdata from Great Britain and the United States. We test a simple hypothesis that families tend to move long distances in favor of the male's career and that this can have a detrimental effect on women's employment status. Unlike many previous studies of this question, our work emphasizes the importance of identifying couples that have migrated together, rather than simply comparing long-distance (fe)male migrants with nonmigrant (fe)males individually. We demonstrate that women's employment status is harmed by family migration; the results we present are surprisingly consistent for Great Britain and the United States, despite differing economic situations and cultural norms regarding gender and migration. We also demonstrate that studies that fail to identify linked migrant couples are likely to underestimate the negative effects of family migration on women's employment status.

Adolescent↗
PubMed2001

Age-related macular degeneration: cost-of-illness issues.

Macular degeneration refers to the breakdown of cells in the centre of the retina. Some degeneration is an inevitable consequence of the aging process; however, when this is associated with loss of sight in the central part of the field of vision an underlying pathology is considered present. Among those aged 55 years, the prevalence of the disease in the US was estimated at 1% rising to approximately 15% among those aged 80 years. Other studies estimate the prevalence of the disease to be higher and to be increasing. The main effect of the disease is to reduce the ability of the individual to engage in everyday activities that require clear central vision. It may also be associated with elevated risks of depression and increased levels of dependency. Currently there is no effective treatment for the majority of patients. For a minority (< 10%) laser photocoagulation therapy may be effective in reducing the risk of severe vision loss. Another treatment, photodynamic therapy, is in development and many others are at an experimental stage. This review sought to establish current knowledge on the cost of illness associated with age-related macular degeneration (ARMD). A search of the literature, together with direct communication with researchers in related fields and patient support/advocacy groups, was undertaken to ascertain current knowledge on the cost of illness of ARMD. While literature on the disease is extensive and literature on treatments is emerging, no substantive information on direct or indirect costs was found although evidence that loss of earnings may occur is beginning to emerge. Some information does exist on cost of illness in diabetic retinopathy, a disease with similarities to ARMD, though even for this disease gaps in knowledge are apparent and wide variations exhibited. Given current knowledge, it is not possible to report on the cost of illness for ARMD with confidence. The lack of information on the cost of illness in ARMD presents difficulties for researchers and policy makers in assessing the cost effectiveness of the existing treatment, as well as new treatments as they become available. Given developments in treatments and the increasing prevalence of the disease, it is important that cost-of-illness information is gathered for ARMD.

Cost of Illness↗