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Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 523 records · Page 29Linked to original sources

Pre- and postnatal growth and protein turnover in four muscles of the rat.

Developmental growth and associated changes in protein turnover and nucleic acid concentrations have been studied in four individual skeletal muscles. They have also been related to changes in the whole animal. The growth rates of both fast and slow muscle types progressively diminished from the fetus to old age. Similarly, the fractional rates of protein synthesis (measured in vivo) and breakdown in each muscle type declined with age; the changes in the former correlating with decreases in the ribosomal capacities of the muscles. Throughout, fast muscles possessed lower turnover rates. The mean half-lives of mixed proteins were 12.0, 14.4, 13.5, and 7.2 days in the extensor digitorum longus (EDL), gastrocnemius, diaphragm, and soleus muscles, respectively, 310 days postpartum. Muscle atrophy was found at 735 days, at which stage the decreased protein synthetic rate in the soleus was due to a fall in the ribosomal capacity, while that in the EDL was attributable to a decreased synthetic rate per ribosome.

Animals↗

Desmethylmisonidazole (Ro 05-9963): clinical pharmacokinetics after multiple oral administration.

The O-demethylated metabolite of misonidazole, Ro 05-9963, has been administered orally, prior to irradiation, to over 50 patients with malignant disease in order to assess the effectiveness of this compound as a hypoxic cell radiosensitizer. This paper reports the pharmacokinetic data observed in those patients who received multiple doses to a total of 12 gm-2. The mean time and magnitude of the peak plasma concentration was determined together with the plasma profile and half-life at the start and finish of each regime of 6, 20, 25 or so fractions. Half-life was independent of drug dose while peak plasma levels rose with increasing amount of drug given. The importance of urinary clearance for this polar drug is indicated by the figure of approximately 50% of administered dose excreted by this route over 24 hours, compared to less than 25% for misonidazole. It was also illustrated by the increased half-life shown by one patient who suffered renal failure during treatment. Peak plasma concentration appeared to be slightly later and were more variable than in the more ideal conditions of the normal volunteer study. In addition, this study confirmed the latter study's findings that absorption is rapid following oral administration of Ro 05-9963, yielding peak plasma levels nearly as high as those seen with misonidazole. Administration in capsules rather than aqueous solution lead to slower absorption, but the peak level did not change.

Administration, Oral↗

Activation of a transposable element in the germ line but not the soma of Caenorhabditis elegans.

The genetic activity of transposable elements is tightly controlled in many species. Transposons that are relatively quiescent under certain circumstances can excise or transpose at greatly increased rates under other circumstances. For example, 'genomic shock' can activate quiescent maize transposons, 'cytotype' and tissue-specific splicing regulate Drosophila P factors, copy number controls Tn5 transposition in bacteria, and developmental timing affects the production of transposon-like intracisternal A-particles in mouse embryos. The Caenorhabditis elegans transposable element Tc1 is subject to both strain-specific and tissue-specific control. Multiple copies of Tc1 are present in the genome of all C. elegans strains collected from nature. However, these elements are genetically active in only certain isolates. For example, in C. elegans variety Bristol transposition and excision of Tc1 are undetectable, but in variety Bergerac transposition and excision are frequent. Moreover, in variety Bergerac, Tc1 is about 1,000-fold more active in somatic cells than in germ cells. We have investigated the genetic basis for the germ/soma regulation of Tc1 activity. We have isolated mutants that exhibit increased frequencies of Tc1 excision in the germ line. The frequencies of Tc1 excision in the soma are unaltered in these mutants. These mutants also exhibit high frequencies of Tc1 germ-line transposition, and this results in a mutator phenotype. Nearly all mutator-induced mutations are caused by insertion of Tc1.

Animals↗

Changes in the referral pattern of child patients from the GDS to the CDS following the introduction of capitation in October 1990. General Dental Services. Community Dental Services.

OBJECTIVE: To observe the changes in the criteria for, rate of, and pattern of, referral of child patients from the General Dental Services (GDS) to the Community Dental Services (CDS) which may have occurred following the introduction of capitation as the method of remuneration for general dental practitioners (GDPs) for the treatment of child patients in The new contract 1990. DESIGN: GDP referral criteria and attitude to capitation were assessed in two districts (North Downs and Weybourne Trusts) using a questionnaire distributed to 179 GDPs. Reasons for referral, and treatment received within the CDS, were collated from the dental records of referred children, before and after the introduction of capitation. RESULTS: The response rate from the GDPs was 87%, of whom 82% had referred child patients to the CDS. The results showed that 65% of GDPs indicated a preference for treatment of children under a fee per item system, whereas only 17% favoured capitation. Although 60% believed that their referral of patients to the CDS had not changed following capitation, an analysis of the referred children's dental records revealed that there had actually been a 57% increase in the number of referrals from GDPs to CDS following the introduction of capitation. The GDPs considered the most important referral criteria were for non cooperation or general anaesthesia. More cooperative children had been referred and more routine restorative procedures, less inhalation sedation and deciduous extractions were carried out following the introduction of capitation. CONCLUSIONS: This study has shown that following the introduction of capitation there had been an increase in the number of referrals from the GDS to the CDS.

Adolescent↗

The influence of case mix, site selection, and methods biases on costs of hospitalization for acute exacerbations of chronic obstructive airways disease and lower respiratory tract infections.

OBJECTIVE: To compare costs of hospitalization for lower respiratory tract infection (LRTI) in patients who received antibiotics before admission to those who did not, and in patients with and without underlying chronic obstructive airways disease (COAD) or diabetes mellitus. METHODS: All hospitalizations in a population of 366,849 residents in Tayside Scotland from 1993 to 1994 were analyzed. Three groups of patients were identified by primary discharge diagnosis in 1993/94 and previous admissions from 1980 to 1992: 1) acute exacerbation of COAD; 2) LRTI plus a secondary diagnosis of COAD or previous admission with COAD; 3) LRTI but no secondary COAD or previous admission with COAD. Setting specific costs were applied (e.g., general medicine, intensive care, geriatrics). Dispensed antibiotic prescribing in the 28 days before admission was identified from all community pharmacies. Nonparametric statistical tests were used. RESULTS: Patients with COAD were more likely to have received antibiotics before admission: COAD (n = 893) 49%; COAD + LRTI (n = 316) 43%; LRTI only (n = 822) 33%. Patients who received antibiotics before admission had lower hospital costs than patients who did not. Mean total costs per admission: COAD pound1604 versus pound1625 (p = .5); COAD + LRTI pound2281 versus pound2297 (p = .5); LRTI only pound2365 versus pound3233; (p = .009). Increasing age and diabetes mellitus were associated with higher hospital costs in all three groups. CONCLUSION: Economic models of the value of preventing hospital admissions for COAD or LRTI will be subject to case mix bias unless they adjust for age, community antibiotic use, and comorbidity.

Journal Article↗

The excess cost of acute exacerbations of chronic bronchitis in patients aged 45 and older in England and Wales.

INTRODUCTION: Chronic Bronchitis is a serious and costly health problem. Prevalence is estimated at 45 per 10,000 persons in the United Kingdom. Approximately 120,000 Pounds would be saved for every 100 hospital admissions avoided. A reduction in acute exacerbations of chronic bronchitis (AECB), treatment failures, and subsequent hospital admission could have a significant impact on the burden of AECB borne by secondary care facilities in the UK National Health Service (NHS). OBJECTIVE: The aim of this study is to provide an economic assessment of the direct cost to the health care system associated with the management of chronic bronchitis and its acute exacerbations. DESIGN: A prevalence-based, excess-cost-of-illness analysis is undertaken from the perspective of the UK NHS. Disease prevalence data, primary health care resource utilization, hospital inpatient and outpatient resource utilization, and costs of health care were taken from a variety of data sources, including a large UK national survey of general practice (GP) consultations, the General Practice Research Database, a survey from a single NHS hospital trust, and the national health-care resource and cost statistics. RESULTS: From 1994 to 1995, approximately 233,000 cases of chronic bronchitis were detected in the persons aged 45 and older in the United Kingdom. Prevalence peaked at 204 per 10,000 in the group of subjects aged 75 to 84 years. During that same period, the total excess cost of primary care associated with AECB was calculated at 35.7 million Pounds. The largest component of primary care costs was the excess cost of all prescription medicines, which totaled 27.8 million Pounds. The excess cost attributed to antibacterial and respiratory prescription medications alone was estimated at 9 million Pounds. Excess costs attributed to GP consultations and hospital emergency room visits were 6.5 million Pounds and 1.3 million Pounds, respectively. The excess costs arising from inpatient hospital episodes included 8.3 million Pounds for hospital admissions, 660,000 Pounds for outpatient costs, and 225,000 Pounds for day care. CONCLUSIONS: These results suggest that improving the management of AECB with the objective of reducing the number of AECB treatment failures and the associated hospital admissions could significantly reduce expenditures by the UK NHS.

Aged↗

Defensible documentation using the endoscopy pathway.

Complete, defensible documentation in a busy endoscopy unit can be elusive. Quick turnaround time, impatient physicians, and add-on and emergent cases all contribute to chaotic days. The endoscopy pathway provides a guided path for succinct documentation by the healthcare worker. A scoring system is initiated on admission. Assessment parameters clearly define scores for vital signs, level of consciousness, abdominal status, pain, safety, and mobility. Scores can be scanned quickly and compared by the nurse to identify significant changes in each patient. Documentation is timely, communicative, and complete. The endoscopy pathway is illustrated by a case study. It reflects patients' progress throughout their stay in the GI unit from admission to discharge. The implementation process of this innovative chart form is presented.

Critical Pathways↗

Plasma concentration--response relationship of verapamil in the treatment of angina pectoris.

Eight patients, mean age 59 years, with stable angina pectoris were investigated with standardized exercise tests to evaluate the plasma concentration--response relationship for verapamil and one of its metabolites, norverapamil. The usual antianginal therapy was discontinued at least 48 h before the start of the investigation. During 4 consecutive days verapamil was administered orally in increasing doses, i.e., no verapamil, 40 mg, 80 mg, or 120 mg t.i.d. Standardized exercise tests were performed each day. In the individual patient the plasma concentration of verapamil increased linearly with the dose given. However, there was a 10- to 30-fold interindividual variation in plasma concentrations of verapamil. The ratio norverapamil/verapamil in plasma decreased with increasing doses of verapamil. The maximal working capacity limited by angina pectoris increased with the plasma concentration of verapamil to a maximum of about 40% for the highest dose. With increasing plasma concentration, the pulse rate decreased both at rest and during exercise. The PQ time increased linearly with the plasma concentration. The systolic and diastolic blood pressure showed a tendency to decrease at the highest plasma levels. Norverapamil seemed not to contribute to the antianginal effect. These results indicate that a correlation exists between the plasma concentration of verapamil and the antianginal effect.

Angina Pectoris↗

Effects of dextromethorphan, a nonopioid antitussive, on development and expression of amygdaloid kindled seizures.

The effects of dextromethorphan (DM), a nonopioid antitussive and a functional N-methyl-D-aspartate (NMDA) antagonist, on expression and development of amygdaloid kindled seizures were examined. The maximum anticonvulsant effect of DM (30 mg/kg) on fully kindled seizures appeared within 30 min of administration and lasted for at least 2 h. DM decreased, in a dose-dependent manner [10-70 mg/kg, intraperitoneally (i.p.)], the severity of kindled seizures 30 min after injection, but the estimated ED50 was 3 times higher than the previously reported value for maximal electroshock convulsions. Furthermore, the high dose (70 mg/kg), while suppressing kindled seizures, produced myoclonus which coincided with EEG spike activity in the amygdala and the cortex. When tested on the development of kindling, 30 mg/kg DM retarded the growth of afterdischarge in the amygdala and the cortex, but had no effect on the development of behavioral seizures. DM 60 mg/kg accelerated development of kindling and produced spontaneous seizures. These results indicate that DM, unlike other NMDA antagonists, has a narrow therapeutic window as an anticonvulsant on kindled seizures and that higher doses may potentiate the kindling process.

Amygdala↗

Rates of mineral loss in human enamel during in vitro demineralization perpendicular and parallel to the natural surface.

Human enamel is a structurally anisotropic material. The aim of this study was to investigate whether this structural anisotropy is reflected in the demineralization behaviour of enamel. Kinetics of demineralization of in vitro caries lesions with the direction of acid attack perpendicular to the natural surface of dental enamel from human premolar teeth were compared with kinetics when demineralized parallel to this surface. Pairs of enamel samples from the same tooth were demineralized under identical conditions. Loss of mineral with time was very nearly linear for both directions (consistent with the rate-controlling step being reaction at the advancing front rather than transport processes), but the perpendicular rate was, on average, about 14% higher than the parallel rate. The rate of demineralization parallel to the surface increased from the natural surface to the enamel-dentine junction by 10-25%, depending on sample. The origin of fine structure and slight departures from linearity in the loss of mineral with time plots are discussed. Mineral masses per unit area were determined from absorption of a 15-microm diameter X-ray beam using photon (AgKalpha) counting methods.

Anisotropy↗

Optical profilometric study of changes in surface roughness of enamel during in vitro demineralization.

The application of non-contact optical profilometry for non-destructive study of changes in the surface roughness of natural enamel surfaces during in vitro demineralization was investigated. Repeated measurement of profiles of the same enamel surfaces after successive demineralization episodes was achieved by a kinematic specimen mount that could be removed, then accurately repositioned. Surface roughness parameters and reflectivity of natural enamel surfaces exposed to either a demineralizing solution (test) or deionized water (control) for up to 6 days were measured at 6- to 24-hour intervals. The results prior to demineralization showed that surface roughness varies with position on the enamel surface. During demineralization there was an approximately linear increase in surface roughness for the first 70 h followed by somewhat erratic behaviour, and a saturating exponential with time increase in reflectivity for the first 70 h which subsequently remained constant. Changes in enamel surface during in vitro demineralization were also observed using scanning electron microscopy.

Dental Enamel↗

Porcine embryonic brain cell cytotoxicity mediated by human natural killer cells.

Intracerebral transplantation of porcine embryonic dopamine-producing neurons has been suggested as a method to treat patients with Parkinson's disease. Even though the brain is an immunologically privileged site, neuronal xenografts are usually rejected within a few weeks. T cells are important for this process, but the exact cellular events leading to rejection are poorly characterized. Brain cells from ventral mesencephalon of 26-27-day-old pig embryos were used as target cells in flow cytometry-assessed cytotoxicity assays using non- and IL-2-activated CD3- CD16+ CD56+ human natural killer (NK) cells as effector cells. The ability of human NK cells to kill pig embryonic brain cells by antibody-dependent cellular cytotoxicity (ADCC) in the presence of nondepleted and anti-Gal alpha1,3Gal antibody-depleted human blood group AB serum (AB serum) was evaluated using the same assay. Both nondepleted and anti-Gal alpha1,3Gal antibody-depleted AB serum could mediate ADCC of pig embryonic VM cells when human NK cells were used as effector cells. Nonactivated NK cells did not show any direct cytotoxic effect on freshly isolated VM cells, whereas IL-2-activated NK cells killed approximately 50% of the VM cells at an effector-to-target ratio of 50:1 in a 4-h cytotoxicity assay. Activation of VM cells by TNF-alpha did not change their sensitivity to human NK cell cytotoxicity. Human NK cells may thus contribute to a cellular rejection of pig neuronal xenografts by ADCC, or following IL-2 activation, by a direct cytotoxic effect.

ABO Blood-Group System↗

Intralesional methylprednisolone for Langerhans' cell histiocytosis of the orbit and cranium.

A 27-month-old girl had a rapidly expanding orbital frontal bone mass due to Langerhans' cell histiocytosis. The CT of the orbit showed a lateral orbital mass containing an irregular density that extended into the intracranial cavity through a lytic lesion of the bone. This is the first report of the use in the orbit of an intralesional steroid injection. Five months later the lesion had not recurred. This treatment spared the patient radiation therapy or a craniotomy with curettage.

Bone Diseases↗