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Biomedical subjects

N Ward

Publications and source records attributed to N Ward.

At least 19 recordsLinked to original sources
PubMed1998

The LEC rat possesses reduced hepatic selenium, contributing to the severity of spontaneous hepatitis and sensitivity to carcinogenesis.

The hepatic concentrations of copper, zinc, magnesium, calcium, and selenium were measured in LEC rats, which develop a spontaneous form of hepatitis at 3-4 months of age, and compared to trace metal concentrations in the LEA rat, its asymptomatic congenic strain. Consistent with results found by other groups, copper was found to accumulate within the liver of LEC rats to levels more than 50 times those measured in LEA rats. In addition, liver selenium concentration in LEC rats was found to be around 50% of that in LEA rats. The enzyme activity, and RNA for the selenium dependent enzyme, glutathione peroxidase, was also found to be reduced in LEC rat liver. These results indicate that hepatic selenium in the LEC rat is depleted and that, as a result of this, the capacity to protect cells from copper-induced free-radical damage is reduced.

Animals↗
PubMed1998

An open-label, multicentre, randomised phase 2 study of recombinant human granulocyte colony-stimulating factor (filgrastim) as an adjunct to combination chemotherapy in paediatric patients with metastatic neuroblastoma.

Administration of combination chemotherapy to children with metastatic neuroblastoma induces profound myelosuppression resulting in chemotherapy treatment delays and febrile neutropenic episodes. The objective of this randomised multicentre study was to assess the incidence, duration and severity of neutropenia when filgrastim is added to induction chemotherapy administered to patients with metastatic neuroblastoma. In this study, 59 patients with metastatic neuroblastoma were randomised to receive chemotherapy (control group, n = 28) or chemotherapy plus filgrastim (filgrastim group, n = 31). Chemotherapy consisted of four cycles of cyclophosphamide, vincristine and doxorubicin (CADO) alternating at 21-day intervals with cisplatin and etoposide (CDDP-VP16). Filgrastim was administered subcutaneously at a dose of 5 micrograms/kg/day from day 7 for up to 14 days. The incidence of neutropenia (absolute neutrophil count [ANC] < 0.5 x 10(9)/l) in the filgrastim group was not reduced after the first CADO course. However, significant reductions were observed after courses 2, 3 and 4. The duration of neutropenia and of intravenous antibiotic use were significantly reduced in the filgrastim group over the whole study period (9 days versus 26 days, P < 0.001; 12 days versus 20 days, P = 0.04, respectively). However, the duration of hospitalisation and the incidence of febrile neutropenia were not significantly reduced. Compliance to treatment was good and the ability to administer chemotherapy without treatment delays was significantly better in the filgrastim group (P < 0.05). Event-free survival was greater in the filgrastim than in the control group (2.4 years versus 1.3 years; P = 0.072). Filgrastim is a beneficial adjunct to combination induction chemotherapy used in the treatment of metastatic neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Neuropsychological outcome of experimental manipulation of phenylalanine intake in treated phenylketonuria.

Blood phenylalanine concentrations were experimentally increased for 3 months by means of a phenylalanine-complemented amino acid supplement in a group of 16 children aged 10-16 years with classical phenylketonuria who had been treated early and who had remained on the restricted diet. Average concentrations achieved during challenge were between 1000 and 1300 mumol/L. Psychological outcome was measured by a neuropsychological battery consisting of tests of verbal and spatial memory, attention and fine motor coordination. A triple-blind, repeated measures, randomized, crossover design was adopted to control for practice and expectancy effects. Subjects were assessed at baseline and at the end of the first and second phenylalanine manipulation periods. Significant interactions (ANOVA) emerged as predicted for phenylalanine concentrations, but similar crossover effects were not found for any of the neuropsychological tests. The results suggested that medium-term hyperphenylalaninaemia in treated PKU is not harmful to psychological functioning in older children and adolescents who have been continuously treated up to and beyond age 10 years, though the susceptibility of executive functions needs to be further researched. The findings add some weight to the idea that by late childhood the vulnerability of the nervous system to the neurotoxic influence of phenylalanine may be much reduced.

Adolescent↗
PubMed1996

In vitro hydrogen production by glucose dehydrogenase and hydrogenase.

A new in vitro enzymatic pathway for the generation of molecular hydrogen from glucose has been demonstrated. The reaction is based on the oxidation of glucose by Thermoplasma acidophilum glucose dehydrogenase with the concomitant oxidation of NADPH by Pyrococcus furiosus hydrogenase. Stoichiometric yields of hydrogen were produced from glucose with the continuous recycling of cofactor. This simple system may provide a method for the biological production of hydrogen from renewable sources. In addition, the other product of this reaction, gluconic acid, is a high-value chemical commodity.

Cloning, Molecular↗
PubMed1996

Filgrastim to treat neutropenia and support myelosuppressive medication dosing in HIV infection. G-CSF 92105 Study Group.

BACKGROUND: Patients with HIV infection frequently experience disease or treatment-related myelosuppression leading to neutropenia. Neutropenia often leads to dose-reduction or discontinuation of important myelosuppressive therapy. OBJECTIVE: To examine the efficacy and safety of filgrastim for reversing neutropenia and determine the effect of this on use of myelosuppressive medications. DESIGN: Open-label, non-comparative, multicentre study in 200 HIV-positive patients with neutropenia [absolute neutrophil count (ANC) < 1.0 x 10(9)/l]. Filgrastim was started at 1 microgram/kg/day subcutaneously for 28 days. This initial treatment phase was followed by a maintenance phase, using 300 micrograms on 1-7 days/week. In both phases the dose of filgrastim was adjusted to achieve an ANC of 2-5 x 10(9)/l. RESULTS: Filgrastim reversed neutropenia in 98% of patients (ANC > or = 2 x 10(9)/l), with a median time to reversal of 2 days (range 1-16) and a median dose of 1 microgram/kg/day (range 0.5-10). Most patients (96%) achieved reversal of neutropenia with a filgrastim dose of < or = 300 micrograms/day (< or = 1 vial/day). Normal ANCs were then maintained with a median of 1 microgram/kg/day (range 0.22-10.6) during the treatment phase and 3 x 300 micrograms vials/week (range 1-7) during the maintenance phase. Ganciclovir, zidovudine, co-trimoxazole and pyrimethamine were the drugs most frequently considered to be causing neutropenia, and 83% of patients received one or more of these in the study. Filgrastim allowed > 80% of patients to increase or maintain dose-levels of these four medications or add them to their therapy. The number of these four medications received per patient increased by > 20% during filgrastim therapy. Filgrastim was well tolerated. CD4, CD8 and total lymphocyte counts all increased slightly, and there was no difference in HIV-1 p24 antigen levels. CONCLUSION: Filgrastim rapidly reverses neutropenia and maintains normal ANC in patients with HIV infection. This allows greater use of myelosuppressive medications without the potentially life-threatening complications of neutropenia.

Adolescent↗
PubMed1995

Unraveling the extent of diversity within the order Planctomycetales.

The phylogenetic positions of 22 isolates that morphologically resemble members of the family Planctomycetaceae were determined by sequence analysis of genes coding for 16S rRNA. While nine and eight isolates could be assigned to the genera Planctomyces and Pirellula, respectively, three strains grouped near Isosphaera pallida and one strain was closely related to Gemmata obscuriglobus. No isolate was found to be related to a previously described species of any of the four genera at the species level. Morphological characters and sequence idiosyncrasies of genes coding for 16S rRNA of the isolates generally correlated with features described for the four genera to which the isolates could be assigned. One strain stands phylogenetically isolated and may be representative of a novel genus of the family. Comparison with environmental clone sequences representing planctomycetes in soil and water revealed that three of the novel isolates were related to one clone of soil origin, but no close relationships between clones and the other new strains were found. The study reveals that the biodiversity of planctomycetes is significantly greater than was previously determined.

Base Sequence↗
PubMed1994

Serum insulin is a risk marker for coronary heart disease mortality in men but not in women.

Serum insulin 1 h post-glucose load is examined in this prospective study of 2971 Caucasoid subjects aged > 20 years in 1966 and followed to 1989. The serum insulin levels as a continuous variable show no significant linear association with coronary heart disease (CHD) deaths in either sex after accounting for age by Cox proportional hazards analysis. In males the quintile classes of serum insulin show a striking U-shaped pattern with both the highest and lowest quintiles having significant associations with CHD deaths. In females the insulin quintiles show no direct association. Analysis for interactions of risk variables indicate that in females the relative protection of low cholesterol levels is abolished by hyperinsulinaemia after 12 years. Thus, serum insulin is not a direct aetiological risk factor for CHD. The findings suggest that the associations are likely to be due to confounding effects of unmeasured variables including lipid subfractions.

Adult↗
PubMed1992

Excitotoxic lesions of the pedunculopontine tegmental nucleus of the rat. II. Examination of eating and drinking, rotation, and reaching and grasping following unilateral ibotenate or quinolinate lesions.

The pedunculopontine tegmental nucleus (PPTg) contains a population of cholinergic neurons thought to be part of the ascending reticular activating system, and non-cholinergic neurons. In the previous study it was shown that various excitotoxins made effective lesions of cholinergic neurons in the PPTg but that quinolinate made smaller lesions in the non-cholinergic population, making it more selective than any other excitotoxin. The purpose of the present experiment was, first, to make lesions of cholinergic neurons throughout the length of the PPTg by infusing toxin at two different sites within it; and second, to examine simple motor activities in rats bearing either quinolinate or ibotenate lesions of the PPTg, and contrast these with the deficits seen after 6-hydroxydopamine (6-OHDA) induced lesions of mesostriatal dopamine (DA)-containing neurons. Post-mortem examination was carried out using choline acetyltransferase (ChAT) and tyrosine hydroxylase (TOH) immunohistochemistry, and routine Nissl staining. Both quinolinate and ibotenate destroyed approximately 75% of ChAT-positive neurons in the PPTg, but damage to non-cholinergic neurons (assessed by Nissl staining) was twice as great following ibotenate as quinolinate. 6-OHDA induced almost complete lesions of mesostriatal DA neurons, assessed by TOH immunohistochemistry. DA depleted rats showed deficits in drinking and spilled more food in the first 2 weeks after surgery, and were unable to reach or grasp food pellets in the staircase test. They also showed strong ipsilateral turning in response to amphetamine and contralateral turning to apomorphine. Quinolinate lesioned rats had no eating or drinking impairment in the home cage but showed a reaching (though not grasping) disability in the staircase test. They had a mild ipsilateral bias following amphetamine. Ibotenate lesioned rats, despite having larger lesions than the quinolinate, showed no deficits in eating or drinking in the home cage, or reaching or grasping disabilities in the staircase test. They did have a mild contralateral bias in response to amphetamine. This dissociation of the effects of quinolinate and ibotenate lesions of the PPTg is consistent with the suggestion that the PPTg has two functionally distinct components, and is attributed to the differential lesion of non-cholinergic neurons by the two excitotoxins.

Animals↗
PubMed1990

Tissue aluminum concentrations stability over time, relationship to age, and dietary intake.

Aluminum concentration was measured in serum, whole blood, hair, and urine by neutron activation analysis. Seventy-six nondemented subjects were investigated. Not all assays were done on all subjects (e.g., serum aluminum on 76 subjects, whole blood aluminum on 42 subjects), but tissue aluminum concentrations were estimated on more than one occasion on 32 subjects. The mean +/- SD aluminum concentration in serum was 0.219 +/- 0.063 micrograms/ml (N = 76), in whole blood 0.368 +/- 0.091 micrograms/ml (N = 42), in urine 0.092 +/- 0.076 micrograms/ml (N = 42), and in hair 6.42 +/- 2.22 micrograms/g (N = 42). Using product moment correlation coefficient there was no significant correlation between age and tissue aluminum concentrations, nor between dietary intake of aluminum and tissue aluminum. The tissue aluminum concentrations were not stable over time even when dietary intake was constant. Tissue aluminum concentrations were measured in 14 patients after 7 days of dietary control and repeated approximately 6 weeks later, again after 7 days of dietary control. There was no significant correlation between the two estimations in any tissue measured. These results suggest that raised tissue aluminum concentrations reported in Alzheimer's disease are not an exaggeration of a normal ageing process, are not likely to be simply secondary to increased dietary aluminum intake, and that Alzheimer's disease does not represent the chronic toxic effect of moderately raised aluminum levels at the upper end of the normal distribution.

Adult↗
PubMed1990

Rapid measurement of basic drugs in blood applied to clinical and forensic toxicology.

A gas chromatographic method is presented to measure blood, serum or plasma concentrations of more than 40 basic drugs. The sensitivity is 0.05 mg/L or less, which represents medium-high therapeutic and overdose concentrations, and in many instances the major active metabolites are also quantified. The paper describes a single step extraction from basic solution into n-butyl acetate containing maprotiline internal standard. Disposable glass tubes are used, with direct chromatography of the upper organic layer. GLC analysis is conducted for 10 min isothermally on a packed column (3% SP2250) with nitrogen-phosphorus detection. The coefficient of variation (CV) of the assay is between 2% and 5%, and data on the reproducibility of retention times are presented.

Calibration↗
PubMed1990

Gas chromatographic measurement of cocaine in serum, plasma and whole blood.

A gas chromatographic method is presented to measure cocaine in serum, plasma or blood. To reduce the in-vitro chemical and enzymic hydrolysis of cocaine, samples should be collected into fluoride oxalate tubes, frozen immediately and stored at -20 degrees C until analysis. Extractions are carried out in disposable glass tubes immersed in an ice-bath. The method uses a single step extraction from a mildly basic solution into n-butyl acetate containing maprotiline internal standard. A portion of the upper organic layer is chromatographed for 5 min isothermally on a packed column (3% SP2250) with nitrogen-phosphorus detection. The coefficient of variation (CV) of the assay is below 6% at 0.1 mg/L and the limit of accurate measurement is 0.02 mg/L. A case of acute cocaine intoxication is described to illustrate the application of the method.

Adult↗
PubMed1990

Ankyloglossia: a case study in which clipping was not necessary.

Following the birth of a baby with a short frenulum, the mother experienced pain from the infant's first feeding that was severe and persistent, despite usually effective interventions. The pain forced the mother to pump her breastmilk and use a feeding bottle and rubber nipple despite her determination to breastfeed. Because the baby's tongue could not extend over the lower gumline, suckling injured all tissue the tongue touched--both the mother's nipples and areolae. Nevertheless, even though this baby's frenulum extended to the tip of the tongue, he was able to adapt his suckling movements to provide good areolar stimulation without persistent nipple damage. Infant growth was not compromised and no surgical intervention was necessary.

Breast↗
PubMed1990

Worldwide status of poliomyelitis in 1986, 1987 and 1988, and plans for its global eradication by the year 2000.

In 1986, a total of 28,951 cases of poliomyelitis were reported to WHO by 175 countries/areas. For 1987, 35,685 cases were reported by 168 countries/areas. Reporting is incomplete for 1988, based on data available as of December 1989. Trends in regional incidence rates for poliomyelitis over a 15-year period from 1974 to 1988 suggest a decline in the incidence of the disease, especially since 1982. However, the reported data underreport actual disease incidence. During 1986, 1987 and 1988, the Expanded Programme on Immunization (EPI) estimates that 200,000-250,000 cases of paralytic poliomyelitis occurred each year. With the current level of polio immunization coverage, it is estimated that 360,000 cases of paralytic poliomyelitis were prevented in 1988. In 1974, when the EPI was started, it was estimated that less than 5% of children in the developing world were adequately immunized against six common childhood diseases, including poliomyelitis. In 1988 (based on data available as of December 1989) 67% of children worldwide received a full course of polio vaccine before 12 months of age. The progress of the EPI has provided optimism that poliomyelitis can be eradicated. In May 1988, the Forty-first World Health Assembly committed WHO to the global eradication of poliomyelitis by the year 2000. The eradication of poliomyelitis will represent, along with the eradication of smallpox, a fitting gift from the XXth to the XXIst century. To reach this goal, action will be required in several main areas. Immunization coverage will need to be raised and sustained in every district. Vaccine quality must be assured by using vaccines which meet WHO requirements and maintaining the cold chain. Surveillance must be strengthened so that prompt, regular reporting of suspected cases leads to disease-containment measures. Additional actions include improving laboratory diagnostic capabilities, developing special training materials, increasing public awareness, supporting rehabilitation services and conducting essential research.

Forecasting↗
PubMed1986

A study of physician preferences in the management of depression in the general medical setting.

Although more than 30% of ambulatory medical patients are depressed, little is known about how their depression is managed in the primary care setting. We surveyed 282 primary care physicians at two internal medicine and four family medicine programs. We asked these physicians to describe how they actually managed depression in their depressed medical patients and how they would manage ten hypothetical depressed medical patients. Demographic and attitudinal data were also obtained. Physicians reported that they utilized a wide variety of treatments for their depressed patients. They indicated that they would recommend counseling twice as many depressed patients as they would recommend medicating or referring. Over 30% of the variance in self-reported preferences to recommend particular treatments for depression was accounted for by physician characteristics. Prior experience with a treatment strategy was a significant factor in predicting a recommendation for future use of a treatment independent of other considerations such as endorsement of positive attitudes about the efficacy or benefits of a treatment. Prior experience was also more important than physician sociodemographics as a predictive variable. The clinical and educational implications of these findings for psychiatrists and primary care physicians are discussed.

Adult↗
PubMed1985

Career orientations of medical and pediatric residents.

Educators have expressed concern about the declining percentage of graduating residents who choose an academic career. This study identifies characteristics of postgraduate physicians that are associated with intentions to pursue an academic career or a full-time private practice. Data were obtained from 299 residents in pediatrics and internal medicine at five academic medical centers in Southern California, using self-report questionnaires. Preference for an academic career was strongest among residents who were most satisfied with their work, were frequently sponsored by faculty, had published, or who either lived alone or were married to another professional. The likelihood of full-time private practice was strongest among residents who were less frequently sponsored by faculty, had not published, lived with others, were from certain medical schools, or were females. Training programs may wish to consider some of these factors in the selection of residents and in program development.

Academic Medical Centers↗
PubMed1984

Antidepressants in concomitant chronic back pain and depression: doxepin and desipramine compared.

Doxepin and desipramine at final doses of 188 and 173 mg/day, respectively, were compared in 36 volunteers with major affective or dysthymic disorder and chronic back pain. Both drugs produced significant decreases in depression, with an overall response rate of 70%; no significant difference was seen between groups. Pain ratings also decreased significantly in both groups (overall response rate = 50%); pain severity showed a better response to doxepin than to desipramine. While baseline pain, depression, and anxiety were correlated, treatment changes in these measures did not correlate. CSF beta-endorphin levels did not change with treatment. The usefulness of an antidepressant with anxiolytic properties, such as doxepin, is discussed.

Adult↗