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S Atkinson

Publications and source records attributed to S Atkinson.

At least 19 recordsLinked to original sources
PubMed2003

A randomised prospective comparison of the Flamingo Wallstent and Ultraflex stent for palliation of dysphagia associated with lower third oesophageal carcinoma.

BACKGROUND: Covered metallic oesophageal stents offer effective palliation of malignant oesophageal strictures. However, first generation devices were associated with a high rate of migration, particularly when used in the lower oesophagus. AIM: To compare the rate of complications and palliative effect of two newer covered metallic oesophageal stents. PATIENTS AND METHODS: We performed a prospective randomised study using two of these newer stent designs in the treatment of malignant lower third oesophageal tumours. Fifty three patients with dysphagia due to inoperable oesophageal carcinoma involving the lower third of the oesophagus were randomly selected to receive either a Flamingo covered Wallstent (Boston Scientific Inc., Watertown, Massachusetts, USA) or an Ultraflex covered stent (Boston Scientific Inc.). Dysphagia was scored on a five point scale, recorded before stent insertion, the day after, and at least one month later at follow up. Technical success, early and late complications (perforation, migration, severe gastro-oesophageal reflux, haematemesis, and reobstruction due to tumour overgrowth) were also recorded. RESULTS: In both stent groups, a significant improvement in dysphagia score was seen both the next day post stenting and at late follow up (p<0.05). No significant difference was seen in the improvement in dysphagia between the two groups (p>0.1). The frequency of complications encountered in the two groups was similar. Three patients in the Ultraflex group required two stents at primary stenting. CONCLUSION: The two types of stent are equally effective in the palliation of dysphagia associated with lower third oesophageal malignancy and the complication rates associated with their use are comparable.

Aged↗
PubMed2002

Chromosomal imbalances in familial chronic lymphocytic leukaemia: a comparative genomic hybridisation analysis.

A subset of B cell chronic lymphocytic leukaemia (CLL) is familial. Lack of large families makes it attractive to exploit methods in addition to genetic linkage analysis for the identification of a susceptibility locus. One strategy that can localise regions of the genome that may harbour tumour suppressor genes is to identify regions of chromosomal imbalance using comparative genomic hybridisation (CGH) analysis. We examined 24 familial CLL cases by CGH analysis. Losses that are documented as arising frequently in sporadic CLL were observed at a comparable frequency in familial CLL. However, gains and losses in two regions of the X chromosome - Xp11.2-p21 and Xq21-qter - appear more common in familial CLL than in sporadic CLL. This suggests these regions may harbour a susceptibility locus for CLL. There is also some evidence that chromosome regions 2p12-p14 and 4q11-q21 may harbour predisposition genes.

Chromosome Aberrations↗
PubMed2002

Detection of cyclin D1 in B cell lymphoproliferative disorders by flow cytometry.

AIMS: To describe and revise a flow cytometric assay for evaluating cyclin D1 overexpression in B cell lymphoproliferative disorders (B-LPDs). METHODS: Cyclin D1 expression was evaluated in 11 healthy controls and 51 patients with B-LPD by flow cytometry using the 5D4 monoclonal antibody. In 25 cases, experiments were repeated up to four times with mononuclear cells (MNC) fixed in ethanol for 1-120 days to evaluate the consistency of cyclin D1 expression. Flow cytometry results were compared with fluorescence in situ hybridisation (FISH) for the t(11;14) translocation in 19 patients and with immunohistochemistry (IHC) using the DCS-6 monoclonal antibody in nine patients. RESULTS: A mean fluorescence intensity ratio (MFIR) of 4.8 was defined as the cut off point for positivity based on cyclin D1 expression in healthy controls (mean + 3 SD). Ten patients overexpressed cyclin D1 by flow cytometry. These included five of eight patients with mantle cell lymphoma, four of 19 with chronic lymphocytic leukaemia, and one with follicular lymphoma. MFIR in the repeat experiments differed less than 25% in 20 of 25 patients and in no cases did it cross the cut off point. There was a good correlation between cyclin D1 expression by flow cytometry and FISH for t(11;14) in 15 of 19 patients and six of nine had concordant results with flow cytometry, FISH, and IHC. CONCLUSION: Cyclin D1 expression remains fairly stable once MNC are fixed in ethanol and the flow cytometric assay can be used for the routine screening of B-LPD. Further comparisons between flow cytometry, IHC, and FISH may be needed to ascertain the diagnostic value of the flow cytometric assay.

B-Lymphocytes↗
PubMed2001

Cyclin D1 by flow cytometry as a useful tool in the diagnosis of B-cell malignancies.

The translocation (11;14)(q13;q32) and its molecular counterpart the BCL-1 rearrangement are features observed in mantle cell lymphoma (MCL) and less commonly in other B-cell disorders. This rearrangement leads to cyclin D1 overexpression, which may be the main pathogenic event in these tumours and is therefore recognised as a diagnostic marker. We developed a flow cytometry method to detect cyclin D1 overexpression using the monoclonal antibody (MoAb) 5D4, and characterised its frequency in 93 B-cell malignancies. The competitive reverse transcriptase polymerase chain reaction (RT-PCR) for cyclin D1, D2 and D3 was then performed on 40 of these cases to assess the validity of the flow cytometry method. Fluorescence in situ hybridisation (FISH) to detect t(11;14)(q13;q32) was carried out on 31 cases and results were compared with cyclin D1 expression by flow cytometry. Twenty five cases showed cyclin D1 expression using 5D4, including MCL (12/13, 92%), chronic lymphocytic leukaemia (CLL) (4/30), B-prolymphocytic leukaemia (B-PLL) (1/4), splenic lymphoma with villous lymphocytes (SLVL) (4/13), hairy cell leukaemia (HCL) (1/7) and other B-non Hodgkins Lymphoma (B-NHL) (3/15). There was a good correlation between flow cytometry results and RT-PCR in 36/40 cases (90%), and with FISH for t(11;14) in 25/31 cases (80%). We concluded that the detection of cyclin D1 expression by flow cytometry in cell suspensions could be applied routinely to the study of B-lymphoproliferative disorders and may be of value for their diagnosis and management.

Biomarkers, Tumor↗
PubMed2001

Use of methoxamine in the resuscitation of epinephrine-resistant electromechanical dissociation.

We describe three cases of electromechanical dissociation under anaesthesia that were unresponsive to doses of intravenous epinephrine given according to current Advanced Life Support guidelines, but which responded immediately to the intravenous administration of the pure alpha agonist, methoxamine. We suggest a possible mechanism to explain this finding and review the literature on vasopressor drugs used for cardiopulmonary resuscitation during electromechanical dissociation. An intravenous alpha agonist, such as methoxamine 20 mg, should be considered for any case of cardiac arrest secondary to electromechanical dissociation which is unresponsive to epinephrine given according to current guidelines.

Adrenergic alpha-Agonists↗
PubMed2001

Deletions of D13S25, D13S319 and RB-1 mapping to 13q14.3 in T-cell prolymphocytic leukaemia.

Deletions of 13q14.3 are well known in several malignancies and are thought to be associated with tumour suppressor function. The RB-1 gene is a tumour suppressor gene, but other loci including D13S319 and D13S25 telomeric to this within 13q14.3 are deleted in B-cell chronic lymphocytic leukaemia (B-CLL), multiple myeloma and non-Hodgkin's lymphoma, with varying clinical significance. The fluorescence in situ hybridization screening of 22 patients with T-prolymphocytic leukaemia (T-PLL) for deletions of 13q14.3 revealed loss of D13S25 in 17 cases (mean 40% range 13-98%), with 11 patients having at least a 20% deletion. Mapping the deletions for the RB-1, D13S319,and D13S25 loci revealed D13S25 as the most frequently deleted marker. However, patients with only the D13S25 deletion had low percentages of cells with the deletion (12-13%), suggesting that loss of D13S25 on its own may not provide sufficient growth advantage. The use of the YAC 954c12, which maps immediately adjacent to D13S25, defined the telomeric border of the deletion in some of the cases. Inv(14)(q11q32) and t(14;14)(q11;q32) are characteristic of T-PLL, but are also observed in premalignant T-cell clones in patients with ataxia telangiectasia. Transition to overt leukaemia may result from loss of suppressor function. Thus, 13q14.3 deletions could contribute to the development of overt leukaemia in T-PLL, but the involvement of more than one gene in the region cannot be excluded.

Adult↗
PubMed2001

Polycythemia vera: analysis of DNA from blood granulocytes using comparative genomic hybridization.

BACKGROUND AND OBJECTIVES: The diagnosis of polycythemia vera (PV) is supported by the finding of an abnormal karyotype in patients with erythrocytosis. However, most PV patients have normal marrow cytogenetics at presentation and there is reluctance to use this test routinely. Comparative genomic hybridization (CGH) is a cytogenetic screening technique that analyzes interphase cells. This approach offers practical advantages over conventional cytogenetics and interphase fluorescence in-situ hybridization (IFISH). We have therefore evaluated the diagnostic utility of CGH applied to blood granulocytes in PV. DESIGN AND METHODS: Blood granulocytes from 17 PV patients were analyzed using CGH and the results compared with those from previous conventional cytogenetics and IFISH studies. RESULTS: Three patients had abnormal CGH profiles. One case had gain of 9p. This patient had normal IFISH results using a centromere-9 probe. The second case had complete gain of chromosomes 8 and 9 and the third had complete gain of chromosome 9, all confirmed by IFISH: Cytogenetics had not been performed in two of these cases and had failed in the third. Three cases with 20q deletion according to cytogenetics and/or IFISH, were normal by CGH. The remaining subjects were normal by all methods. INTERPRETATION AND CONCLUSIONS: CGH analysis of blood granulocytes can detect the chromosome gains commonly observed in PV. However, CGH cannot be relied on to detect 20q deletions, which are the most frequent cytogenetic abnormality in PV. Thus, CGH has a role in the diagnosis and follow-up of PV patients, but must be used in conjunction with other methods.

Adult↗
PubMed2000

A single amino acid change makes a rat neuronal sodium channel highly sensitive to pyrethroid insecticides.

Two amino acid substitutions in a housefly sodium channel, L1014F in domain IIS6 and M918T in the IIS4-S5 linker, have been identified in kdr and super-kdr pyrethroid-resistant phenotypes, respectively. Unlike their native insect counterparts, mammalian sodium channels are only weakly sensitive to pyrethroids. Do the sodium channels of mammal and pyrethroid-resistant housefly share similar structural characteristics that account for their low pyrethroid sensitivities? We report here that substitution of isoleucine for methionine at position 874 (equivalent to the super-kdr site 918 in the housefly) in the rat IIA alpha-subunit causes a 100-fold increase in sensitivity.

Amino Acid Sequence↗
PubMed2000

Concentrations of progesterone in milk from bottlenose dolphins during different reproductive states.

There are few published reports of an alternative, less invasive method than blood sampling to obtain reproductive hormone concentrations from captive dolphins. The aims of this study were to: (1) validate milk as an effective alternative to blood plasma for determining progesterone concentrations; and (2) utilize milk samples collected frequently to obtain progesterone concentration profiles and determine reproductive status. During the course of this study 16 plasma/milk sample pairs were collected from four adult bottlenose dolphins to correlate plasma and milk concentrations of progesterone. Milk samples were also collected approximately weekly for 4-5 months during three independent lactational periods. Additionally, milk samples were collected daily for approximately 1 year during three other independent lactational periods. A highly significant correlation was found between progesterone concentrations in plasma and milk (r(2) = 0.91, P < 0. 01). Progesterone contained in milk whey, fat, and solids were 3.95 +/- 1.3, 8.5 +/- 1.1, and 52.0 +/- 0.6%, respectively. Progesterone profiles from milk samples collected from two dolphins during 1995 indicated pregnancies (with progesterone concentrations between 8 and 46.5 ng/ml) which resulted in parturition. High progesterone concentrations in a third dolphin that did not give birth indicated a possible pseudopregnancy or fetal resorption. A possible ovulation not resulting in pregnancy was evident in one female in 1998, follicular activity in another female in 1998, and a year-long anestrous period in the third animal studied in 1998. It is confirmed that dolphins can become pregnant while lactating and that the approximate time of conception is identifiable in milk profiles, illustrating the potential application of this method in pregnancy detection and reproductive monitoring.

Anestrus↗
PubMed2000

Going down to the local: incorporating social organisation and political culture into assessments of decentralised health care.

The social organisation and political culture of the society in which an organisation is embedded can have major effects on the way in which organisational policy is implemented and on how that organisation functions. Research on health sector reforms has paid scant attention to this aspect. If the claims made for decentralised management in the health sector are to be evaluated seriously, it is critical to develop concepts and methods to evaluate not only the formal organisation and the outputs of the health system, but also the aspects of local social organisation and political culture within which that local health system is embedded that may mediate their relationship. The paper explores three cases of district health systems in Northeast Brazil in order to identify aspects of local social organisation and political culture that appear to influence the implementation of the reforms and thereby potentially impact upon the quality of the care provided. The results of the study indicate the importance that aspects of local social organisation and political culture may exert on the operations of a decentralised health system. Key aspects identified are: the space for autonomy; the space for local voice in political life; personalized and institutionalised influences on autonomy and local voice; differences of involvement of health staff with the district; different spaces of acceptable practice and accountability. These factors are seen to moderate the intent of the health reforms at all stages in their implementation. Three possibilities are discussed for the nature of the interaction in terms of cause and effect between the formal organisation of the health system and its local context. Seeing this relationship as one of a dialogue offers some cautious optimism for the potential of the reform agenda. The paper closes with suggestions on how to take this line of research forward.

Brazil↗
PubMed2000

Acute severe pancreatitis and multiple organ failure: total parenteral nutrition is still required in a proportion of patients

AIMS: Enteral nutrition (EN) is increasingly advocated as the favoured means of nutritional support in patients with multiple organ failure resulting from acute severe pancreatitis. In a proportion of patients, however, EN may not be feasible either because of gastrointestinal stasis and high nasogastric aspirates or because of superseding complications of pancreatitis such as fistulation. In these cases total parenteral nutrition (TPN) is indicated. METHODS: Patients with acute severe pancreatitis admitted to the intensive care unit (ICU) were commenced on either nasogastric or, where established, jejunostomy EN. Rates of EN were controlled by protocol and volumes of nasogastric aspirate. TPN was commenced when volumes of EN were persistently inadequate or when this route was contraindicated (e.g. high-volume small bowel fistula). Physiological and outcome data were collected prospectively and included severity of illness scoring (Acute Physiology and Chronic Health Evaluation (APACHE) II), length of stay, duration of EN and TPN, and hospital outcome. RESULTS: Of 69 patients with acute severe pancreatitis, 31 were transferred from other ICUs. The median APACHE II score was 18 (range 4-40) and the overall hospital mortality rate was 39 per cent. Seventeen patients (25 per cent) were managed with EN alone, ten (14 per cent) with TPN alone and 19 (28 per cent) with a combination of both. Twenty-three (33 per cent) did not have any nutritional support during their ICU stay. The mortality rate was worse among patients who received TPN only than in those who had EN (60 versus 24 per cent). CONCLUSIONS: EN is likely to remain the route of choice for nutritional support in the ICU. However, in high-risk patients with acute severe pancreatitis EN may not be feasible and TPN is often required. This may reflect a greater severity of illness.

Journal Article↗
PubMed2000

Monocyte-derived macrophage cytokine responses induced by M. bovis BCG.

SETTING: One important aspect of macrophage function is the production of inflammatory and anti-inflammatory cytokines, which in turn affect the survival of intracellular organisms such as mycobacteria. OBJECTIVE: To determine the relationship between phagocytosis of mycobacteria and expression of intracellular cytokines. DESIGN: Phagocytosis and cytokine production were studied simultaneously within human monocyte-derived macrophages (MDMs) from healthy donors using fluorescent labelling of M. bovis BCG and flow cytometry. RESULTS: At a range of infection ratios (5:1, 1:1, 0.2:1) TNF- alpha, IL-10, IL-6 and IL-12 were all produced in a dose-dependent manner. At an infection ratio representative of the in vivo situation (1:1), cytokine production was induced in both MDMs containing intracellular M. bovis BCG and in uninfected bystander MDMs. Phagocytosis increased over time, but there was considerable donor variation: the proportions of cells containing one or more mycobacterium were 15.4+/-14.8% (mean+/-SD) at 4 h and 32.7+/-21.1% at 24 h (n=19). Analysis of cytokine production by MDMs not containing mycobacteria (bystander cells) at 4 h revealed that these uninfected cells produced 79+/-6.6% of the TNF- alpha, 53.9+/-40.0% of the IL-10 and 64.2+/-12.4% of the IL-12. By 20 h these proportions had decreased to 57+/-13.5%, 30.9+/-7.4% and 45.5+/-13.3% respectively. CONCLUSION: Both infected and bystander MDMs can be stimulated to produce cytokines in response to M. bovis BCG, indicating that the ability of MDMs to produce cytokines is not necessarily dependent on the ability to phagocytose mycobacteria.

Adult↗
PubMed2000

Role of Rho in Ca(2+)-insensitive contraction and paxillin tyrosine phosphorylation in smooth muscle.

We investigated whether Rho activation is required for Ca(2+)-insensitive paxillin phosphorylation, myosin light chain (MLC) phosphorylation, and contraction in tracheal muscle. Tyrosine-phosphorylated proteins have been implicated in the Ca(2+)-insensitive contractile activation of smooth muscle tissues. The contractile activation of tracheal smooth muscle increases tyrosine phosphorylation of the cytoskeletal proteins paxillin and focal adhesion kinase. Paxillin is implicated in integrin-mediated signal transduction pathways that regulate cytoskeletal organization and cell motility. In fibroblasts and other nonmuscle cells, paxillin tyrosine phosphorylation depends on the activation of Rho and is inhibited by cytochalasin, an inhibitor of actin polymerization. In permeabilized muscle strips, we found that ACh induced Ca(2+)-insensitive contraction, MLC phosphorylation, and paxillin tyrosine phosphorylation. Ca(2+)-insensitive contraction and MLC phosphorylation induced by ACh were inhibited by C3 transferase, an inhibitor of Rho activation; however, C3 transferase did not inhibit paxillin tyrosine phosphorylation. Ca(2+)-insensitive paxillin tyrosine phosphorylation was also not inhibited by the Rho kinase inhibitor Y-27632, by cytochalasin D, or by the inhibition of MLC phosphorylation. We conclude that, in tracheal smooth muscle, Rho mediates Ca(2+)-insensitive contraction and MLC phosphorylation but that Rho is not required for Ca(2+)-insensitive paxillin tyrosine phosphorylation. Paxillin phosphorylation also does not require actomyosin activation, nor is it inhibited by the actin filament capping agent cytochalasin D.

ADP Ribose Transferases↗
PubMed2000

Comparative response in growth and bone status to three dexamethasone treatment regimens in infant piglets.

The objectives of this study were 1) to determine whether a zenith in bone formation (indicated by circulating osteocalcin) existed at night in early life, and 2) to compare the effects of three different dexamethasone (DEX) treatment regimens on bone turnover, bone mineral content, and growth. Three DEX treatment regimens were tested in 8-d-old piglets (n = 8/group): 1) low evening dose of DEX (0.5 mg/kg/d) as 70% in the morning and 30% in the evening for 10 d; 2) tapering course of DEX (0.5, 0.3, and 0.2 mg/kg/d) as 50% in the morning and 50% in the evening for 14 d; and 3) constant dose of DEX (0.5 mg/kg/d) as 50% in the morning and 50% in the evening for 10 d. Oral water placebo groups were tested with the same time courses. At pretreatment, plasma osteocalcin was significantly higher (p < 0.05) at 0100 than at 0900 and 1700. At necropsy, measures for DEX groups were calculated as Z-scores using values from the placebo groups. The low evening DEX dose led to a significantly lower reduction in plasma osteocalcin compared with the tapered and constant dosing regimens (p < 0.05). The significant weight. reduction in the DEX group occurred at d 9 in the low evening dose regimen but at d 7 in the constant dosing regimen, compared with the placebo group. Bone mineral content Z-score was reduced similarly in all DEX-treated groups across the three dosing regimens. We conclude that a plasma osteocalcin zenith at night exists in early life. A high DEX dose in the morning and low DEX dose in the evening may partially attenuate corticosteroid-induced suppression of bone formation and growth restriction.

Animals↗
PubMed1999

Serum T(4) and serum T(3) concentrations in immature captive whitetip reef sharks, Triaenodon obesus.

Serum T(3) (3,5,3' triiodothyronine) and serum T(4) (thyroxine) concentrations were repetitively assayed by radioimmunoassay over a three-year period in two male and two female immature captive whitetip reef sharks, Triaenodon obesus. These sharks were maintained at the Waikiki Aquarium, Honolulu, Hawaii, in an open system holding pool receiving 568 liters per minute of water from a saltwater well with an iodide concentration of 0.076 mg/liter. No significant male-female difference was observed for either serum T(3) or serum T(4). No seasonal pattern of serum T(3) was detected (P = 0.07). Serum T(3) concentrations ranged (mean +/- SEM) from 0. 52 to 0.83 ng/mL (0.67 +/- 0.01; n = 64). A significant seasonal difference was observed for serum T(4) (P < 0.001). Serum T(4) concentration was higher in winter (October-January) with a mean (range +/- SEM) of 6.58 ng/mL (1.48-8.77 +/- 0.35; n = 24) and lower in summer (May-August) with a mean of 3.62 ng/mL (1.34-5.71 +/- 0. 22; n = 24). The thyroid hormone T(4) has a seasonal rhythm even in immature sharks and may have an important role in physiology. J. Exp. Zool. 284:500-504, 1999.

Animals↗
PubMed1999

Cytotoxic T lymphocytes can induce a condemned state and synchronous post-mitotic apoptosis of daughter target cells.

We have used time-lapse video microscopy to study cytotoxic T lymphocyte (CTL)-mediated apoptosis of LDb fibroblast target cells at different phases of the cell cycle. When aphidicolin-synchronized target cells were exposed to the CTL clone F5, apoptosis occurred with similar morphology during G1, S/G2 and M phase, showing that apoptosis and mitosis are not mutually exclusive cellular events. Interestingly, following normal mitosis of target cells that had been previously contacted by CTL, pairs of daughter cells would occasionally undergo apoptosis within minutes of each other. Such synchronous post-mitotic apoptosis was also observed when using mitotically unsynchronized target cells, and also when using d11S T cell hybridomas as alternative Fas- (CD95-) based effector cells, even if these effectors were physically washed away after an initial period of co-incubation with the target cells. Our observations show that cytotoxic cells can induce a condemned state in pre-mitotic target cells, which can be inherited by both daughter cells, leading to their synchronous apoptosis after mitosis.

Animals↗