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Biomedical subjects

J Nichol

Publications and source records attributed to J Nichol.

At least 19 recordsLinked to original sources
PubMed2005

An anomaly in the isotopomer shift of the hyperfine spectrum of LiI.

A high-precision examination of the hyperfine spectrum of 6LiI in comparison with 7LiI shows a shift in the iodine nuclear electric quadrupole moment that cannot be accounted for by a model in which the electric field gradient at the iodine site is assumed to depend only upon the internuclear distance between Li and I. The other hyperfine interactions are consistent between the two isotopomers, including the previously reported electric hexadecapole interaction of the iodine nucleus.

Journal Article↗
PubMed2002

Pathology of cultured paua Haliotis iris infected with a novel haplosporidian parasite, with some observations on the course of disease.

Mortalities among juvenile paua Haliotis iris Martyn 1784 in a commercial culture facility were reported in April 2000. Histology of moribund paua showed heavy systemic infections of a uni- to multi-nucleate stage of a novel organism later confirmed by transmission electron microscopy (TEM) and molecular studies to be a haplosporidian. Multinucleate plasmodia up to 25 microm diameter with up to 17 nuclei were detectable in wet preparations of hemolymph from heavily infected paua. The presence of the haplosporidian in the affected facility was associated with mortalities of slow growing 'runt' paua during the summer months. Total mortalities in affected raceways 6 mo after mortalities began were between 82.5 and 90%. Heavily infected paua exhibited behavioural abnormalities including lethargy, loss of righting reflex, and were easily detached from surfaces. Some heavily infected paua exhibited oedema and pale lesions in the foot and mantle, but no reliable gross signs of disease were noted. Light infections of the haplosporidian were also found in apparently healthy paua from the facility. Histology indicated that the early stages of infection were characterised by small numbers of plasmodia in the connective tissue surrounding the gut, amongst glial cells adjacent to nerves in the mantle and foot and within gill lamellae. In heavy infections, large numbers of small plasmodia (mean size 5.5 x 7 microm in histological sections) were present in the hemolymph, gills, heart, kidneys, mantle, foot, epipodium and connective tissue of the digestive gland. Infections were not transferred horizontally at 14 and 19 degrees C after cohabiting heavily infected paua with uninfected paua for 3 mo in aquaria, or 3 mo after injecting healthy paua with hemolymph containing haplosporidian plasmodia. This may indicate that the prepatent period for disease is longer than 3 mo, that disease is not expressed below 20 degrees C, or that an intermediate host is required for transmission. Spore formation was not observed in juvenile paua but sporocyst-like bodies containing putative spores were observed amongst haplosporidian plasmodia in the right kidney of poorly performing adult paua collected from the wild.

Animals↗
PubMed2000

Thrombopoietic cytokines in relation to platelet recovery after bone marrow transplantation.

In order to evaluate the importance of different thrombopoietic stimulatory cytokines in accelerating platelet recovery after bone marrow transplantation (BMT), we assayed serial plasma concentrations of three cytokines, thrombopoietin (TPO), interleukin-6 (IL-6), and IL-11 through the course of platelet nadir and recovery after BMT. Both mean TPO and IL-6 levels showed a marked rise and later fall preceding or coincident with the platelet nadir and recovery, suggesting their potential role as circulating regulators or stimulators of thrombopoiesis. In contrast, IL-11 levels remained remarkably constant through the whole course suggesting that this cytokine, though capable of stimulating thrombopoiesis, does not serve as a circulating regulator of platelet production. Additionally, we assayed the levels of these three cytokines following initial platelet transfusion to assess the capacity of transfused platelets to adsorb these thrombopoietic cytokines from the plasma and reduce their circulating levels, thus potentially modifying their availability for stimulating megakaryocyte proliferation. No consistent falls in TPO, IL-6 or IL-11 levels were observed following the initial two platelet transfusions. These data support the importance of circulating TPO and IL-6 as hormones capable of stimulating platelet production. Their physiologic relevance as in vivo regulators of thrombopoiesis and clinical utility for therapy of thrombocytopenia need further investigation.

Adult↗
PubMed1999

What is the real clinical utility of echocardiography? A prospective observational study.

This was a prospective, structured interview to evaluate physician expectations of echocardiography and the subsequent impact on patient care. The setting involved requests for echocardiograms in patients admitted to a tertiary care teaching hospital. Measurements included assessment of the diagnostic and therapeutic implications of echocardiography perceived by the physicians and subsequently reported and confirmed by blinded chart review. From January to May 1997, 542 echocardiograms were performed on 500 inpatients (age 62 +/- 17 years; 56% men). Referring physicians were mainly house staff (83%) and from medical services. The main indications were evaluation of left ventricular function (54%) or valve function (16%). At the time of the request, 89% of physicians believed that echocardiography was needed to guide future investigations or treatment, although in 24% of cases, physicians could not provide details of such. A reported change in treatment occurred in 57% and was validated by chart review in 38%. Changes occurred more frequently in patients in the intensive care unit versus those not in the intensive care unit (54% vs 37%, P =.02) but were similar between attending physicians and house staff (frequency of change 41% vs 39%, P = not significant) and between those with and those without previous echocardiograms (38% vs 39%, P = not significant). The utility of the echocardiogram to influence treatment decisions in hospitalized patients is high, especially in critically ill patients. However, this impact is less than is anticipated at the time of the initial request. Further studies involving more select populations of patients are required.

Clinical Competence↗
PubMed1999

Spontaneous and cytokine-induced thrombocytopenia in myelodysplastic syndromes: serum thrombopoietin levels and bone marrow morphology. Scandinavian MDS Group, Sweden and Norway.

Thrombocytopenia is a substantial clinical problem for patients with myelodysplastic syndromes (MDS). Cytokine treatment for granulocytopenia and anaemia may further reduce the platelet counts. We studied serum thrombopoietin levels (S-TPO) in 52 patients with MDS and 96 healthy controls and related the results to clinical and morphological variables. S-TPO was also assessed after treatment with granulocyte-CSF (G-CSF) and erythropoietin (EPO) in 30 of these patients. S-TPO in MDS was not a normally distributed variable; mean value was 394 pg/ml, SD +/-831 and median value 123 (12-5000 pg/ml). The controls showed lower S-TPO levels than the patients (median 78 pg/ml, P = 0.003) whereas no differences between the MDS subgroups were observed (P = 0.86). Patients with ringed sideroblastic anaemia (RARS) showed the highest platelet counts and higher S-TPO levels than the controls (P = 0.005). No association between platelet counts and S-TPO levels was found in the patients (P = 0.67). TPO levels were generally low in patients with refractory anaemia with an excess of blasts (RAEB), but very high levels were found in five patients. Patients with a high transfusion need had higher S-TPO levels, whereas bone marrow blast counts, cellularity or megakaryocytes showed no correlation with S-TPO. Patients with 5q- showed lower TPO levels than the other patients, indicating that thrombopoietin is not a mediator of thrombocytosis in these cases. Treatment with G-CSF + EPO significantly reduced the platelet counts (P = 0.0002), but this change was not related to significant changes in S-TPO levels or morphology. Patients with RARS and thrombocytosis who normalized their platelet counts showed a concomitant reduction in S-TPO. This may suggest that the increased platelet counts observed in RARS may be caused by increased S-TPO levels. In conclusion, our study shows that platelet, megakaryocyte and thrombopoietin regulation is rather complex in myelodysplastic syndromes and that spontaneous or induced thrombocytopenia are not usually mirrored by increased S-TPO levels.

Aged↗
PubMed1999

Effect of recombinant human megakaryocyte growth and development factor coupled with polyethylene glycol on the platelet storage lesion.

BACKGROUND: Platelet production is regulated by a thrombopoietic growth factor (Mpl ligand). The receptor for this platelet growth factor (Mpl) is expressed on the platelet surface membrane. A recombinant thrombopoietic cytokine, recombinant human megakaryocyte growth and development factor coupled with polyethylene glycol (PEG-rHuMGDF), was added to apheresis platelets in vitro to determine whether Mpl ligand-receptor binding produced any beneficial or adverse effect on the development of the platelet storage lesion during 5 days of storage. STUDY DESIGN AND METHODS: This study was designed as a dose-response protocol to determine the effects of adding increasing concentrations of PEG-rHuMGDF (0.0 [control], 2.5, 25, and 250 ng/mL) to apheresis platelets stored in two types of plastic storage containers. The increasing concentrations of PEG-rHuMGDF used simulated the theoretical peak plasma level attained in vivo, with an intravenous dose of 0, 0.1, 1.0 and 10 microg per kg of PEG-rHuMGDF. The platelets were stored with agitation at 20 to 24 degrees C for 5 days. A battery of in vitro assays was performed on storage Days 1 and 5, including pH, blood gases, platelet count, lactate dehydrogenase, mean platelet volume, glucose, lactate, osmotic recovery, morphology score, CD62P, and one-dimensional polyacrylamide gel electrophoresis analyses. RESULTS: Analysis of results on both Day 1 and Day 5 showed no significant differences among any of the three PEG-rHuMGDF doses and the control group, for any in vitro assay. One-dimensional polyacrylamide gel electrophoresis showed no changes among the platelet protein patterns for the three PEG-rHuMGDF doses studied or the control. Storage-induced changes, however, did occur equally in all four groups of platelets over the 5 days of storage. CONCLUSION: The addition to stored apheresis platelets of up to 10 microg per kg of PEG-rHuMGDF (250 ng/mL), followed by 5 days of storage at standard conditions, does not appear to promote or retard development of the platelet storage lesion.

Blood Glucose↗
PubMed1997

Thrombopoietin measurement in thrombocytosis: dysregulation and lack of feedback inhibition in essential thrombocythaemia.

Essential thrombocythaemia (ET), a myeloproliferative disorder (MPD) manifested by excessive platelet production, lacks a specific diagnostic test to facilitate differentiation from other thrombocytoses. We studied thrombopoietin (TPO) levels in 41 patients with thrombocytosis: 25 ET patients, eight with other MPD, and eight with reactive thrombocytosis. Mean age and platelet counts for these groups were comparable. TPO levels for 96 healthy individuals provided a reference range for normal. The majority of ET patients (19/25 or 76%) had normal TPO levels. No patient with ET had a TPO level below 75 pg/ml, compared with 57% of healthy donors and 8/16 (50%) patients with other thrombocytoses (P<0.05). TPO levels in ET are not appropriately down-regulated, as occurs with cytokines relevant to other MPD. In thrombocytosis, a TPO level <75 pg/ml indicates that ET is unlikely.

Adolescent↗
PubMed1996

The role of megakaryocyte growth and development factor in terminal stages of thrombopoiesis.

Thrombopoietin (TPO), the ligand for the c-Mpl cytokine receptor, is a recently identified cytokine with potent effects on platelet production. The receptor-binding portion of c-Mpl ligand is encompassed in another molecule known as megakaryocyte growth and development factor, or MGDF. Although it is clear that the administration of TPO or MGDF to animals dramatically increases the platelet count, the specific stage(s) of thrombopoiesis during which these molecules are principally active have not been unambiguously determined. Pharmacology studies administering MGDF at doses ranging from 0.1 to 630 micrograms/kg/d to mice revealed a biphasic response in platelet production. Administration of the drug at concentrations from 6 to 60 micrograms/kg/d resulted in platelet counts 5-fold above normal. However, doses > 60 micrograms/kg/d resulted in less-than-optimal platelet production. This phenomenon was investigated in vitro. Using an established culture system for the generation of human megakaryocytes and platelets, MGDF was shown to be optimally and equivalently active in the generation of mature megakaryocytes at concentrations from 10 to 1000 ng/ml. However, the cytokine was not required for proplatelet formation and in fact was inhibitory to that process in a dose-dependent manner. When MGDF was added to human megakaryocytes at concentrations of 200 ng/ml or greater, proplatelet formation was inhibited to 30% of control values. MGDF-mediated inhibition was specific, since the addition of the truncated form of the c-Mpl receptor reversed the inhibition in a dose-dependent manner. Other recombinant factors, interleukin-6, interleukin-11 and erythropoietin had no significant positive or negative effects in this human proplatelet assay. Together, these data suggest that although TPO and MGDF promote the full spectrum of megakaryocyte growth and development, they are not necessary for proplatelet formation, and may in part regulate platelet shedding by their absence.

Animals↗
PubMed1994

Survey on domiciliary oxygen by concentrator in England and Wales.

Long-term oxygen therapy is initiated in England and Wales by the patient's family doctor, sometimes at the request of a hospital consultant. Guidelines for therapy exist but are not mandatory. We wish to investigate the numbers and types of patients being treated under this regimen, the method of treatment and how they responded to their oxygen dose. We therefore interviewed and tested patients at the inception of therapy in six of the nine prescribing areas of the whole country, during August 1990 and February 1991. Main outcome measures were diagnoses, daily duration and flow prescribed, arterial oxygen saturation (SaO2) breathing air and improvement in arterial oxygen saturation on prescribed oxygen. Most patients both in summer and winter reported diagnoses of chronic bronchitis (45%) or emphysema (50%), in addition to other conditions. Most were male (58%), and most (72%) were over retirement age. Roughly half (45%) were house-bound, but only 28 (6%) were totally bedridden. Three quarters (77%) reported that a hospital consultant had told them how much oxygen to use, and in all diagnostic groups mean prescriptions exceeded 15 h.day-1 and 2 l.min-1. However, only half (54%) of the patients with complete measurements had basal arterial oxygen saturation of 90% or less at the start of treatment, together with a satisfactory improvement in arterial oxygen saturation on the prescribed flow of oxygen. In conclusion, patients are usually prescribed adequate regimens but little attempt is made to ensure that prescription is appropriate or response satisfactory. Resources continue to be used for treating patients without ensuring that they benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Almitrine bismesylate and oxygen therapy in hypoxic cor pulmonale.

The effect of oral treatment with the thiazine derivative almitrine bismesylate was studied in 28 patients with chronic obstructive pulmonary disease and arterial hypoxaemia receiving long term domiciliary oxygen therapy in a placebo controlled, double blind crossover trial. The initial treatment was given for three months and the second for two months. Because almitrine had an unexpectedly prolonged washout effect crossover analysis could not be performed; data from the placebo treatment administered in the second arm of the trial were used to calculate the half life of almitrine. Nine patients were withdrawn from the study (5 almitrine, 4 placebo). Patients' tolerance of the drug was good. The estimated plasma half life of almitrine was 20.5 days, considerably longer than previously reported. Almitrine caused a significant improvement in arterial oxygen tension (PaO2) with a mean maximum increase of 0.7 kPa at a plasma concentration of 500 ng/ml. Higher plasma concentrations were not associated with any further increase in PaO2. There was no significant effect on arterial carbon dioxide tension (PaCO2). In a second, acute study at the end of each arm of the chronic trial nine patients were subjected to increasing oxygen delivery rates (2, 4, and 6 l/min) for 90 minutes or until blood gas concentrations plateaued. Almitrine increased PaO2 in a dose dependent fashion at all delivery rates, but the effect diminished as PaO2 approached normoxic levels. There was no significant effect on PaCO2. Almitrine treatment results in a significant improvement in PaO2 over that achieved by oxygen alone, an effect that diminishes at high flow rates. Whether this is of clinical benefit is not known. In view of the prolonged half life revised dosage schedules are required.

Almitrine↗
PubMed1985

Pretreatment with chemotherapy in patients with advanced head and neck cancer.

Average survival for advanced head and neck cancer (AHNC) is 18 months. In an attempt to improve this we treated 29 AHNC patients between 1978-82 with two courses of chemotherapy. Chemotherapy consisted of cyclophosphamide, methotrexate, 5 fluorouracil and bleomycin; or bleomycin, cisplatinum and methotrexate. Chemotherapy was given prior to definitive therapy of radiotherapy or radiotherapy and surgery. All patients were stage 3 or 4. All patients were Eastern Co-operative Oncology Group status performance 0 or 1. Response to chemotherapy did not improve survival. Pretreatment with chemotherapy should be investigational until increased survival has been documented.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Ocular and oculodermal melanocytosis.

Thirty-three cases of ocular (27) or oculodermal (6) melanocytosis were reviewed to determine the ocular structures involved by the melanocytic hyperpigmentation. The hyperpigmentation was clinically documented to involve all quadrants of the eye in the majority of the subjects; however, nine persons had sectorial involvement. The choroid and episclera were involved diffusely or sectorially in all the subjects, and the anterior chamber angle and iris were involved in most cases. The conjunctiva, lens and optic disc were less frequently involved. Ten persons had a uveal malignant melanoma in the hyperpigmented eye, and in three of the cases the melanoma had arisen in the hyperpigmented sector. Melanocytic involvement of the trabecular meshwork was not clinically correlated with elevated intraocular pressure.

Eye↗
PubMedDate not supplied

Migration of polyisobutylene from polyethylene/polyisobutylene films into foods during domestic and microwave oven use.

Migration of polyisobutylene from polyethylene/polyisobutylene film into foods has been studied in domestic applications such as wrapping of foods and reheating in a microwave oven. The results of these migration studies were obtained by direct measurement using newly developed analytical methods utilizing nuclear magnetic resonance (NMR) and infra-red (IR) spectroscopy as well as predictively from assessment of loss of polyisobutylene from the film. Total levels of polyisobutylene migration into cheese were found to be 8-10 mg/kg, into cake 1-5 mg/kg, and into sandwiches ranged from < 1 to 4 mg/kg. Reheating foods covered with film in the microwave oven, gave migration levels ranging from < 0.01 mg/kg for contact with steam only, up to 0.5 mg/kg for severe splashing of food onto the film and 4 mg/kg for reheated pizza. Migration of polyisobutylene was shown to be skewed towards the low molecular weight fraction of the additive. In typical films, the molecular weight range of polyisobutylene was shown to be 300-6000 daltons (95% limits) centred on 1300 daltons, whereas the additive that had migrated into cheese was found to range from 130-2200 daltons, centred on 520 daltons.

Adipates↗
PubMedDate not supplied

Migration from plasticized films into foods. 6. Hydrolysis of polymeric plasticizers under simulated gastric and intestinal conditions.

The polymeric plasticizers poly(butylene adipate) and poly(propylene adipate), and a low molecular weight oligomer fraction from each, were exposed in vitro to simulated gastric and intestinal hydrolysis in order to study their likely fate after ingestion of foods contaminated by migration from plastics packaging. Analysis for loss of the parent compounds indicated that partial hydrolysis occurred under simulated gastric conditions, with the low molecular weight oligomers being the most susceptible. Analysis for one of the starting materials, adipic acid, revealed however that the hydrolysis did not result in a significant conversion to free monomer under either simulated gastric or intestinal conditions. This is explained on the basis of partial hydrolysis of the plasticizers to smaller oligomer units but with the more resistant ester linkages resisting complete breakdown to monomer.

Adipates↗