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Biomedical subjects

N Jackson

Publications and source records attributed to N Jackson.

At least 19 recordsLinked to original sources
PubMed2001

Ornithine decarboxylase and thymidine kinase activities and polyamine levels from selected organs of adult miniature swine receiving three concentrations of dietary menhaden oil.

Mature, female swine were randomly assigned to one of seven dietary groups. Swine in groups 1-3 were fed a cholesterol-rich diet for 55 days while the remaining groups remained on a basal swine diet. At the end of the cholesterol(Chol)-preloading period the swine in groups 1-7 were placed on menhaden oil (MO) and/or corn oil (CO) as follows: groups 1 and 4, 15% CO (control); groups 2 and 5, 0.75% MO+14.25% CO; groups 3 and 7, 15% MO; and group 6, 7.5% MO+7.5% CO. Animals were killed at the end of the approximately 6-month feeding period and portions of liver, pancreas and colon mucosa were analyzed for both ornithine decarboxylase (ODC) and thymidine kinase (TK) activity while polyamine levels were measured in the liver and pancreas. Statistical analyses were carried out by one-way and two-way ANOVA and by trend analysis. In the pancreas, the highest MO group (group 7) had significantly higher ODC levels when compared with the CO control (group 4) and the next to highest MO group (group 6) (one-way ANOVA)-all non-cholesterol preloaded groups. Using a two-way ANOVA (Chol-by-MO), liver ODC was significantly lower in the CO control when compared with the lowest and highest MO groups (groups 5 and 7, respectively), again in the non-cholesterol-preloaded animals. In the colon, the swine in the Chol-low MO group (group 2) had significantly lower TK activity than the Chol/CO control group (group 1) and Chol/Hi MO group (group 3) (one-way ANOVA) and also had significantly lower activity than all groups except the CO control (group 4) (two-way ANOVA). Liver acetylputrescine in the lowest and highest MO groups (groups 5 and 7, respectively) was significantly higher than in the CO group (group 4). Liver spermidine in the Chol-Hi MO group (group 3) was significantly higher than the Chol-Lo MO group (group 2), while the highest MO group (group 7) had a statistically higher level than the other non-cholesterol groups (groups 4-6) (one-way ANOVA). Liver spermine was significantly higher in the Chol-Hi MO group (group 3) when compared to the CO control (group 1) and the Chol-Lo MO group (group 2) (one-way ANOVA). Pancreatic putrescine in the CO control (group 4) was significantly higher than all other groups (two-way ANOVA) while spermine from the 2 Chol-MO groups (groups 2 and 3) was higher than the Chol-CO control (group 1) (one-way ANOVA). Using trend analysis, liver TK, putrescine and spermidine increased in the non-cholesterol preloaded groups with increasing dietary MO, similar to the increase seen in ODC. Thus, of the three organs studied, only liver responded to menhaden oil with changes in both ODC itself or some of its metabolic engendered products and thymidine kinase; at least for one of the parameters, ODC, change associated with dietary MO was dependent on whether the swine were preloaded with cholesterol.

Animals↗
PubMed2001

Physical sequelae of caesarean section.

The complications and recovery from caesarean section are dominated by the medical condition of the woman pre-operatively. Evidence regarding risks directly attributable to the caesarean section is scanty, and often derived from obstetric practice that differs from the current day. Mortality associated with the procedure is anything up to five times that for vaginal delivery, with emergency caesarean section associated with almost twice the risk of elective procedures. Data regarding placenta praevia and placenta praevia-accreta come from population series where antibiotics were not routinely used for caesarean section, but there is no doubt that previous caesarean section increases the risk of both. Antibiotic and thromboprophylaxis at the time of caesarean section decrease morbidity in the index pregnancy, but can also reasonably be expected to reduce future pregnancy complications.

Adult↗
PubMed2001

mAKAP and the ryanodine receptor are part of a multi-component signaling complex on the cardiomyocyte nuclear envelope.

The physical association of regulatory enzymes and ion channels at relevant intracellular sites contributes to the diversity and specificity of second messenger-mediated signal transduction in cells. mAKAP is a scaffolding protein that targets the cAMP-dependent protein kinase A and phosphodiesterase type 4D3 to the nuclear envelope of differentiated cardiac myocytes. Here we present data that the mAKAP signaling complex also includes nuclear envelope-resident ryanodine receptors and protein phosphatase 2A. The ryanodine receptor is the major cardiac ion channel responsible for calcium-induced calcium release from intracellular calcium ion stores. As demonstrated by a combination of immunohistochemistry and tissue fractionation, mAKAP is targeted specifically to the nuclear envelope, whereas the ryanodine receptor is present at both the sarcoplasmic reticulum and nuclear envelope intracellular membrane compartments. At the nuclear envelope, a subset of cardiac ryanodine receptor is bound to mAKAP and via the association with mAKAP may be regulated by protein kinase A-mediated phosphorylation. By binding protein kinase A and ryanodine receptor, mAKAP may serve as the scaffold for a cAMP- and calcium ion-sensitive signaling complex.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

A foot care program for diabetic unilateral lower-limb amputees.

OBJECTIVE: To assess the efficacy of a specialist foot care program designed to prevent a second amputation and to assess peripheral vascular disease (PVD) and peripheral neuropathy in diabetic unilateral lower-limb amputees. RESEARCH DESIGN AND METHODS: Investigations were carried out in 143 diabetic lower-limb unilateral amputees referred to a subregional rehabilitation center for prosthetic care from a catchment area of approximately 3 million people. Peripheral vascular and nerve assessment, education, and podiatry were provided for each patient. RESULTS: For the patients referred to the foot care program, there were no baseline differences between the patients who proceeded to a bilateral amputation (n = 22) and those who remained as unilateral amputees (n = 121) in their level of foot care knowledge and mean neuropathy scores. Mean ankle-brachial pressure index was significantly lower for the bilateral amputees (0.75 +/- 0.04) compared with the unilateral amputees (0.90 +/- 0.03, mean +/- SEM, P < 0.05), but there was no difference in the level of oxygen in the skin. However, the level of carbon dioxide was significantly lower in patients with bilateral amputation (24.21 +/- 2.16 vs. 31.20 +/- 0.85 mmHg, P < 0.03). Overall, the establishment of a specialist foot care program made no impact on contralateral limb amputation (22 of 143, 15.4%) compared with matched patients without the program (21 of 148, 14%) over a 2-year outcome period for each patient. CONCLUSIONS: PVD is more closely associated with diabetic bilateral amputation than neuropathy or level of foot care knowledge. Preventative foot care programs for diabetic unilateral amputees should therefore place greater emphasis on peripheral vascular assessment to identify patients at risk and on the development of timely intervention strategies.

Aged↗
PubMed2001

Peripheral vascular and nerve function associated with lower limb amputation in people with and without diabetes.

Multiple factors, including peripheral vascular disease and neuropathy, contribute to the development and perpetuation of complications of the lower extremities in diabetes. The main aim of the present study was to assess the peripheral vascular and nerve status of diabetic and non-diabetic subjects that had undergone lower limb amputation. Various non-invasive tests of peripheral vascular and nerve function were carried out on subjects who had undergone unilateral lower limb amputation and were now attending a Rehabilitation Centre. The control group (n=23), the diabetic amputee group (n=64) and the non-diabetic amputee group (n=32) were age-matched. Only the diabetic amputee group had evidence of medial arterial calcification. Transcutaneous oxygen levels were significantly lower in the diabetic amputee group (median 43 mmHg; interquartile range 33-49 mmHg) than in the control (59; 56-74 mmHg) and non-diabetic amputee (57; 43-65 mmHg) groups (control compared with diabetic amputee group, P<0.001; diabetic amputee compared with non-diabetic amputee group, P<0.01). The same trend was found for carbon dioxide levels in the skin [mmHg: diabetic amputees, 25 (21-37); controls, 38 (32-42); non-diabetic amputee, 34 (31-39)] (control compared with diabetic amputee, P<0.01; diabetic amputee compared with non-diabetic amputee, P<0.05). Vibration and pressure perception measurements (which assess Abeta nerve fibre function) showed that both the diabetic amputee and non-diabetic amputee subjects had significantly greater impairment than the controls. However, measures of Aalpha and C nerve fibre function were abnormal only in the diabetic amputee group. Thus the peripheral vascular and nerve functions of age-matched diabetic and non-diabetic subjects having undergone lower limb amputation show specific differences, with non-diabetic amputees exhibiting signs of neuropathy. This indicates that factors characteristic of diabetes (such as hyperglycaemia and non-enzymic glycation) are associated with calcification, lower oxygen and carbon dioxide levels in the skin, and abnormal Aalpha and C nerve fibre function.

Aged↗
PubMed2000

Inhibin expression in normal and pre-eclamptic placental tissue.

Serum inhibin levels increase during normal pregnancy, but are significantly higher in patients with pre-eclampsia. The aim of this study was to demonstrate possible increased expression of inhibin within the placentas of women with pre-eclampsia compared with non-pre-eclamptic controls. Cellular expression of inhibin alpha and beta A subunits was studied using immunohistochemistry on formalin-fixed, paraffin-embedded placental sections from cases of pre-eclampsia (n = 23) and gestational age-matched non-pre-eclamptic controls (n = 16). Immunohistochemistry was performed using monoclonal antibodies against inhibin alpha and beta A subunits by the indirect immunoperoxidase technique. Intensity of staining was graded by a semiquantitative scoring method. Differences in distribution and intensity of staining between control and pre-eclamptic placentas were analyzed using a nonparametric Mann-Whitney U test. Staining for both inhibin alpha and beta A was predominantly confined to the cytoplasm of syncytiotrophoblast, with weak expression within intermediate trophoblast. The intensity of staining for inhibin alpha was significantly greater in the syncytiotrophoblast of pre-eclamptic patients (mean staining intensity controls = 0.97, disease = 1.87; p < 0.001). Inhibin beta A staining was generally stronger than for the alpha subunit, and was also significantly increased in pre-eclamptic patients compared with controls (mean controls = 1.72, disease 2.19; p < 0.05). This is the first evidence for increased placental inhibin presence in pre-eclampsia, suggesting increased inhibin production within the placenta, a finding that could account for increased serum inhibin levels in pre-eclampsia.

Cytoplasm↗
PubMed2000

IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp.

Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I axis. Such abnormalities include decreased circulating levels of IGF-I. We studied the effects of IGF-I therapy (40 microg x kg(-1) x day(-1)) on protein and glucose metabolism in adults with type 1 diabetes in a randomized placebo-controlled trial. A total of 12 subjects participated, and each subject was studied at baseline and after 7 days of treatment, both in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Protein and glucose metabolism were assessed using infusions of [1-13C]leucine and [6-6-2H2]glucose. IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P < 0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05). After IGF-I treatment, a decrease in the overnight insulin requirement (0.26+/-0.07 vs. 0.17+/-0.06 U/kg, P < 0.05) and an increase in the glucose infusion requirement were observed during the hyperinsulinemic clamp (approximately 67%, P < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin-stimulated peripheral glucose disposal was observed after IGF-I therapy (37+/-6 vs. 52+/-10 micromol x kg(-1) x min(-1), P < 0.05). IGF-I administration increased the basal metabolic clearance rate for leucine (approximately 28%, P < 0.05) and resulted in a net increase in leucine balance, both in the basal state and during the hyperinsulinemic amino acid clamp (-0.17+/-0.03 vs. -0.10+/-0.02, P < 0.01, and 0.25+/-0.08 vs. 0.40+/-0.06, P < 0.05, respectively). No changes in these variables were recorded in the subjects after administration of placebo. These findings demonstrated that IGF-I replacement resulted in significant alterations in glucose and protein metabolism in the basal and insulin-stimulated states. These effects were associated with increased insulin sensitivity, and they underline the major role of IGF-I in protein and glucose metabolism in type 1 diabetes.

Adult↗
PubMed1999

Effects of sildenafil citrate on human hemodynamics.

Nitric oxide (NO) induces the formation of intracellular cyclic guanosine monophosphate (cGMP) by guanylate cyclase. Sildenafil, which selectively inhibits phosphodiesterase type 5 (PDE5) found predominantly in the corpora cavernosa of the penis, effectively blocks the degradation of cGMP and enhances erectile function in men with erectile dysfunction. The NO-cGMP pathway also plays an important role in mediating blood pressure. It is, therefore, possible that the therapeutic doses of sildenafil used to treat erectile dysfunction may have clinically significant effects on human hemodynamics. Three studies were undertaken to assess the effects of intravenously, intra-arterially, and orally administered doses of sildenafil on blood pressure, heart rate, cardiac output, and forearm blood flow and venous compliance in healthy men. A fourth study evaluated the hemodynamic effects of intravenous sildenafil in men with stable ischemic heart disease. In healthy men, significant (p <0.01) decreases in supine systolic and diastolic blood pressures were observed with intravenous sildenafil (20, 40, and 80 mg) at the end of the infusion period when plasma levels of sildenafil were highest (mean decreases from baseline of 7.0/6.9 and 9.2/6.7 mm Hg, for the 40- and 80-mg doses, respectively). These changes were transient and not dose related. Modest reductions in systemic vascular resistance also were observed (maximum decrease 16%), although heart rate was not affected by sildenafil administration when compared with placebo. Single oral doses of sildenafil (100, 150, and 200 mg) produced no significant changes in cardiac index from 1-12 hours postdose between placebo- and sildenafil-treated subjects. The approved dosage strengths of sildenafil citrate are 25 mg, 50 mg, and 100 mg. The 80-mg intravenous dose and the 200-mg oral dose of sildenafil produced comparable plasma levels at twice the maximum therapeutic dose (recommended range, 25-100 mg). After brachial artery infusion of sildenafil (up to 300 microg/min), there was a modest vasodilation of resistance arteries and a reversal of norepinephrine-induced preconstriction of forearm veins. These hemodynamic effects were similar to but smaller in magnitude than those of nitrates. In a small pilot study of men with ischemic heart disease, decreases from baseline in pulmonary arterial pressure (-27% at rest and -19% during exercise) and cardiac output (-7% at rest and -11% during exercise) were observed after 40-mg intravenous doses of sildenafil. Sildenafil was well tolerated by subjects and patients in all studies, with headache and other symptoms of vasodilation the most commonly reported adverse effects of treatment. Modest, transient hemodynamic changes were observed in healthy men after single intravenous or oral doses of sildenafil even at supratherapeutic doses. In men with stable ischemic heart disease, sildenafil produced modest effects on hemodynamic parameters at rest and during exercise.

Administration, Oral↗
PubMed1999

Why is acute leukemia more common in males? A possible sex-determined risk linked to the ABO blood group genes.

Acute leukemia is more common in males at almost every age, and this fact remains unexplained. A study was carried out in northeast peninsular Malaysia, where the population is predominantly Malay, to examine whether there was a difference in ABO blood group distribution between males and females with acute leukemia (AL). The ABO blood groups of 109 male and 79 female patients with AL (98 ALL, 90 AML) were compared with those of 1019 controls. In the control population, 39.7% were group O. Among males with AL, 39.4% were group O, whereas among females with AL, the proportion was 24.1% (p=0.03). The same trend to a lower proportion of group O among females was seen if the group was divided into adult/pediatric or lymphoblastic/myeloblastic groups, though these differences were not statistically significant. If these findings can be confirmed, they suggest the presence of a "sex-responsive" gene near to the ABO gene locus on chromosome 9, which relatively protects group O women against AL, at least in our population. The existence of such a gene might also partly explain why acute leukemia, and possibly other childhood cancers, are more common in males.

ABO Blood-Group System↗
PubMed1999

Developing the role of the generic healthcare support worker: phase 1 of an action research study.

This paper reports on the first phase of an action research practice development project to explore, develop and evaluate the role of the generic healthcare support worker in a high dependency rehabilitation service. The project is being jointly conducted by staff from the University of Southampton, the University of Portsmouth and the Isle of Wight Healthcare NHS Trust and phase 1 is supported by a grant from the NHS Executive (South and West). The aim of phase 1 of the project is to explore the attitudes of staff towards the implementation of the role of the generic healthcare support worker, particularly regarding the practical, professional and ethico-legal problems of the role. Professional and support staff from different parts of the service were interviewed in groups and the interviews were tape recorded, transcribed and subjected to a simple thematic analysis. Four themes emerged from the data relating to the challenge to professional boundaries, being a generic worker, outcomes for service and patients and implementing the role. As an action research project, the aim was not to produce findings that are generalizable beyond the practice areas in which they were generated, but it is nevertheless hoped that the reader might be able to apply some of the conclusions to his or her own setting.

Attitude of Health Personnel↗
PubMed1999

Reversal of human neutrophil survival by leukotriene B(4) receptor blockade and 5-lipoxygenase and 5-lipoxygenase activating protein inhibitors.

Persistent neutrophilia is a feature of chronic obstructive pulmonary disease (COPD). Leukotriene synthesis inhibitors and cysteinyl leukotriene receptor antagonists have shown efficacy in the treatment of asthma. Antagonism of leukotriene (LT)B(4) receptors is being considered as a mode of treating COPD. We examined the capacity for inhibition of leukotriene synthesis and LTB(4) receptor antagonism to reduce survival of neutrophils from patients with COPD and those from normal subjects. The basal apoptosis level of these cells was 55.4 +/- 2.4% (mean +/- SEM) of total cells. Separate exposure to lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), dexamethasone (DEX), and LTB(4) increased neutrophil survival (p < 0. 001). The LTB(4) receptor antagonist SB201146 abolished LPS-induced survival in a concentration-dependent manner (10 pmol to 0.1 microM), with an IC(50) of 1.9 nM. Combined exposure to SB201146 and to the cysteinyl leukotriene antagonist SKF104353 did not have a greater effect on survival than did exposure to SB201146 alone. Inhibition of 5-lipoxygenase (5-LO) with BWA4C and of 5-LO-activating protein (FLAP) with MK886 abolished GM-CSF- and DEX-induced neutrophil survival. BWA4C and MK886 abolished GM-CSF- induced neotrophil survival in a concentration-dependent manner (1 nM to 10 microM), with IC(50) values of 182.0 nM and 63.1 nM, respectively. These findings demonstrate reversal of LPS-, GM-CSF-, and DEX-induced neutrophil survival by LTB(4) receptor antagonism and inhibitors of 5-LO and FLAP. They also suggest a potential additional antiinflammatory mode of action of these compounds through reduction of cell survival.

5-Lipoxygenase-Activating Proteins↗
PubMed1999

Postpartum haemorrhage.

Postpartum haemorrhage can be either primary (within 24 hours of delivery) or secondary (within the following weeks). This article reviews the factors that may help anticipation of postpartum haemorrhage, and looks at issues involved in the management and treatment of women with this condition.

Female↗
PubMed1998

Pattern and morphogenesis in skin.

Models dealing with the development of hair and feather follicles commonly predict that the factors initiating morphogenesis also specify patterns of follicle distribution. The factors have been postulated as chemical or mechanical instabilities which, at certain threshold concentrations, determine both the location of follicles and their form. The models tend to focus on the earliest waves of induction, where follicles develop at separate, non-randomly spaced initiation sites in skin. However, in many animals, there are later waves of initiation, some of which give rise to compound follicles. These are bundles of follicles that arise by branching from the necks of those formed earlier and share a common pilary canal when mature. In some species, compound follicles make the greatest numerical contribution to the follicle population. Measurements of the frequencies of single and branched follicles in sheep selection lines with different follicle densities (from previous studies by Moore et al.) revealed that the follicles which formed first during foetal life (primary and original secondary populations) were established at separately identifiable sites in the skin, called here "initiation sites". However, there were also later waves of development, contributing follicles exclusively by the process of branching (the derived secondary population). Final follicle densities were not correlated with the densities of initiation sites. The observations suggested that mechanisms specifying the positional values of initiation sites differed from those determining follicle number. The final densities of the follicle populations in the sheep lines were also highly negatively correlated with the diameters of the wool fibres grown. The close statistical relationship suggested that the two parameters were developmentally linked. However, whereas fibre characteristics are realised when the follicle is mature, density is established earlier, during foetal life. We have reconciled these observations with the following hypothesis: a population of cells, committed to a follicular pathway of development, differentiates in the skin at or before the first wave of initiation. Subpopulations of the committed cells subsequently participate in each follicle initiation event, the number in each subpopulation ultimately determining fibre dimensions. Follicle initiation continues until most or all of the original population have been utilised. Transplantation and skin recombinant studies have demonstrated that the cells forming the dermal papilla of the follicle participate in follicle initiation and have inductive effects on epidermal tissue. Papilla size is also correlated with fibre diameter in the mature follicle. These attributes are consistent with those described for the committed cell population.

Animals↗
PubMed1998

Prognostic significance of retinopathy at presentation in adult acute leukemia.

Retinal changes are common in adult acute leukemia patients at presentation, but their prognostic significance is controversial. A 5-year study has been carried out with newly diagnosed acute leukemia patients aged 12-77 years. Seventy-seven cases (49 AML, 28 ALL) were studied prospectively for the presence of intraretinal hemorrhages (IRH), white-centered hemorrhages, cotton-wool spots, and macular hemorrhages. They were treated according to standard chemotherapy protocols, and then achievement of complete remission (CR) and the duration of overall survival (OS) were compared between the groups with and without these different retinal features. No association was found between the presence of any retinal abnormality and CR induction rate, although there was a trend to a lower CR rate among patients with IRH. The median OS of those with IRH was 72 days, compared with 345 days among those without IRH (p=0.002). A WBC at presentation greater than 50x10(9)/l and age greater than 40 years were also associated with shorter OS (p<0.0001 and p=0.0045, respectively). However, after regression analysis, IRH remained statistically significant as a poor prognostic indicator (p=0.01). We conclude that the presence of IRH is an indicator of poor prognosis in acute leukemia.

Acute Disease↗
PubMed1998

Severe thalassaemia intermedia: clinical problems in the absence of hypertransfusion.

In many of the parts of the world where thalassaemia is common, the blood supply is inadequate or unsafe, and desferrioxamine is too expensive for routine use. We classify some patients as having 'severe thalassaemia intermedia', i.e. those with moderately severe thalassaemia who can survive without regular transfusions, but who are at risk of many complications which are reviewed here. These include bone deformity and fractures, extramedullary haemopoietic tumours, leg ulcers, autoimmune haemolysis and, especially after splenectomy, thromboembolism and infection. An increase in the quality and safety of the blood supply, and a cheaper and/or oral iron chelator, would enable more of these patients to be treated as thalassaemia major and have improved survival and quality of life.

Blood Component Transfusion↗