Dopamine: from Cinderella to Holy Grail.
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Animals↗
Biomedical subjects
A Mills
Publications and source records attributed to A Mills.
The economic evaluation of malaria control technologies: the case of Nepal.
This paper illustrates the methodological issues arising from the use of economic evaluation in a developing country context, and how economic evaluation can be applied in developing countries to draw conclusions of relevance to policy-makers. The paper reports research on the cost-effectiveness of the malaria control programme in Nepal. It outlines the heirarchy of choices presented by malaria control and concentrates on the evaluation of the mix of routine strategies employed by the programme, particularly for vector control and case detection and treatment. A social perspective is taken, and emphasis placed on identifying costs falling on households, namely private expenditure on treatment and loss of days of work. Conclusions are drawn relating to the application of economic evaluation methodology to disease control programmes in developing countries.
Communicable Disease Control↗
Auricular granuloma annulare. A consequence of trauma?
Localized granuloma annulare (GA) is a cutaneous disorder characterized by the formation of palisading necrobiotic granulomas. Although trauma and vasculitis have been considered, the etiology of most cases remains obscure and the disease is generally considered to be idiopathic. The condition may occur at any age and at any site, but usually involves the hands or feet of children or young adults, predominantly affecting females. We present two cases occurring as nodules involving the external ears of males. One of these showed a bilateral distribution and was clearly related to trauma.
Adult↗
Umbilical cord prolapse through a transverse uterine synechia.
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Adult↗
The effect of malaria on work time: analysis of data from two Nepali districts.
Malaria patients' loss of effective work time can account for an important proportion of the disease's economic cost. Here the extent, incidence and determinants of this loss are investigated. Data from 695 matched patient-control pairs from Nawal Parasi and Dhanusa districts in Nepal are analysed. Pairwise differences in work time are attributed to malaria, and the individual influences of the differences' determinants identified by regression. The mean pairwise differences in the number of days wholly and partially disabled by illness in the month preceding interview were respectively 5.31 (95% confidence interval 4.82-5.79) and 1.21 days (95% CI 0.95-1.47). The interval between fever onset and presumptive treatment, parasite species, the density of peripheral parasitaemia and district of residence each exerted significant influences over the difference in complete disability. The mean pairwise difference in the number of minutes worked on the day before the interview was 108 (95% CI 97-120). Socioeconomic variables, the interval between interview and perceived complete recovery, the pairwise difference in the number of days' complete disability in the month preceding interview and district of residence were significant to this difference. Poorer patients lose more time. The results corroborate past assumptions of debility, demonstrate that malaria's effect on effective work time may vary between socioeconomic groups, and underline the economic importance of speedy case detection and presumptive treatment.
Absenteeism↗
Novel non-productively bound ribonuclease inhibitor complexes--high resolution X-ray refinement studies on the binding of RNase-A to cytidylyl-2',5'-guanosine (2',5'CpG) and deoxycytidylyl-3',5'-guanosine (3',5'dCpdG).
The X-ray structures of two complexes of bovine ribonuclease-A produced by soaking pre-grown crystals in solutions of the inhibitors cytidylyl-2',5'-guanosine (2',5' CpG) and deoxycytidylyl-3',5'-guanosine (3',5'dCpdG) have been determined at 1.5 A resolution and refined by restrained least squares to R = 21.0% for 17,855 reflections, and R = 19.1% for 16,347 reflections, respectively. Binding of the substrate analogs to the protein has taken place in a completely unexpected and previously unreported manner. In each case the guanine base occupies the well characterized B1 pyrimidine binding site adjacent to Thr-45 (described by Richards, F.M., Wyckoff, H.W., Carlson, W.D., Allewell, N.M., Lee, B. and Mitsui, Y. (1971) Cold Spring Harbor Symp. Quant. Biol. 36, 35-54, and others including Palmer, R.A., Moss, D.S., Haneef, I. and Borkakoti, N. (1984) Biochim. Biophys. Acta 785, 81-88) having entered through a secondary channel external to the active site itself. We designate this reversed non-productive mode as retro-binding. In this mode of binding the SO4(2-) anion bound in the active site of the native protein crystals (Borkakoti, N., Moss, D.S. and Palmer, R.A. (1982) Acta Crystallogr. B38 2210-2217) has not been displaced by the phosphate of the inhibitor molecule as originally anticipated and observed in other studies. Instead the CMP or dCMP moiety of the inhibitor molecule is held loosely in a channel running towards the surface of the protein molecule and is thus completely external to the active site. Consequently, although it has been possible to model them, no attempt has been made to refine either the disordered cytosine in the CpG complex or the deoxycytosine in the dCpdG complex. The traditional B2 purine binding site of RNase (Richards et al., 1971) is unoccupied by the soaked inhibitors. Important changes that have taken place in the protein structure include: stabilization of both Lys-41 and Gln-11 via H-bonding to SO4(2-); stabilization of His-119 in the A conformation (Borkakoti, N., Moss, D.S. and Palmer, R.A. (1982) Acta Crystallogr. B38 2210-2217); and stabilization of SO4(2-) by H-bonds formed with the retro-bound guanine base. Binding of the inhibitors and stabilization of the active site is accompanied by displacement and redistribution of solvent molecules.
Animals↗
Exempting the poor: the experience of Thailand.
Fee exemption schemes are widely recommended but little analysed. This paper analyses the operation of the Free Medical Care Project in Thailand, which enables those classified as poor to receive free treatment at government facilities. The paper concentrates in particular on the size and geographical distribution of the group eligible for free care, and on the extent to which the geographical distribution of the budget matches the geographical distribution of the poor. By analysing published data available at national level, information is produced on numbers of people eligible for free care, on the numbers who receive free care, and on the geographical distribution of the free medical care budget. Comments are also made on how the project appears to be operating at health facility level. The paper goes on to consider whether the equity effects of the project could be improved by reorganizing the project, and what impact reorganization might have on the costs of the project.
Budgets↗
Recombinant bovine neurokinin-2 receptor stably expressed in Chinese hamster ovary cells couples to multiple signal transduction pathways.
Neurokinins are a family of neuropeptides with widespread distribution mediating a broad spectrum of physiological actions through three distinct receptor subtypes: NK-1, NK-2, and NK-3. We investigated some of the second messenger and cellular processes under control by the recombinant bovine NK-2 receptor stably expressed in Chinese hamster ovary cells. In this system the NK-2 receptor displays its expected pharmacological characteristics, and the physiological agonist neurokinin A stimulates several cellular responses. These include 1) transient inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ mobilization, 2) increased out put of arachidonic acid and prostaglandin E2 (PGE2), 3) enhanced cyclic AMP (cAMP) generation, 4) increased de novo DNA synthesis, and 5) an induction of the "immediate early" genes c-fos and c-jun. Although NK-2 receptor-mediated IP3 formation involves activation of a pertussis toxin-insensitive G-protein, increased cAMP production is largely a secondary response and can be at least partially attributed to autocrine stimulation by endogenously generated eicosanoids, particularly PGE2. This is the first demonstration that a single recombinant neurokinin receptor subtype can regulate, either directly or indirectly, multiple signal transduction pathways and suggests several potential important mediators of neurokinin actions under physiological conditions.
Animals↗
Polarized distribution of coated pits and coated vesicles in the rat lens: an electron microscopy and WGA-HRP tracer study.
The presence and distribution of coated pits (CPs) and coated vesicles (CVs) in the rat lens were studied by thin-section electron microscopy (TEM) and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) as a tracer. TEM revealed that CPs and CVs were approximately 150 nm in diameter, of which the characteristic clathrin coat was approximately 20 nm thick. CPs and CVs were found in both epithelium and superficial fiber cells of the entire lens, and were distributed preferentially along the basal membrane facing the lens capsule. It was estimated that more than 80% of CPs and CVs in the entire epithelium were seen along the basal membrane. The number of CPs and CVs along the basal membrane in the equatorial epithelium (4.4 per 10 microns membrane) was similar to that at the central zone (3.8 per 10 microns membrane), but there was a significant increase along the apical and lateral surfaces of the equatorial epithelium compared to that of the central epithelium, although the overall number was considerably smaller. In the lens fibers, CPs and CVs were usually found within 2-3 superficial layers of fiber cells. The number of CPs and CVs along the basal membrane of young fibers at the post-equatorial region (3.1 per 10 microns membrane) was 3-fold greater than that of the mature fibers at the posterior polar area (1 per 10 microns membrane). Thus, CPs and CVs along the entire basal membrane showed a gradual decrease in number from the anterior (and equatorial) regions to the posterior polar surface of the lens. WGA-HRP experiments showed that approximately 80% of tracer-carrying pits and vesicles were also found along the basal surface of the equatorial epithelium. This study suggests that a polarized distribution of CPs and CVs along the basal surface of epithelium and superficial fiber cells may facilitate receptor-mediated endocytosis of important macromolecules directly from the aqueous humor and vitreous body into metabolically active lens cells.
Animals↗
Chronic androgen treatment increases action potential duration in the electric organ of Sternopygus.
The quasi-sinusoidal electric organ discharge (EOD) of the weakly electric fish Sternopygus is involved in communication and orientation. Each monophasic pulse of the low-intensity EOD is a compound action potential (AP) from the simultaneously firing electrocytes of the electric organ. EOD frequency is lower and EOD pulse duration longer in sexually mature males than in sexually mature females; exogenous androgen lowers EOD frequency and increases EOD pulse duration. In order to determine the contribution of single electrocyte spikes to the entire EOD pulse, APs were induced by intracellular current injection in single electrocytes of isolated pieces of electric organ. Each AP looks very similar to the externally recorded EOD pulses, and AP duration (APD) is significantly correlated with EOD pulse duration (r = 0.48; p less than 0.0005). The APD is slightly longer when compared to the EOD pulse duration, but this difference is likely due to the stimulation paradigm. Fish treated with dihydrotestosterone showed a decrease in EOD frequency, increase in EOD pulse duration, and corresponding increase in APD; control fish showed random, insignificant changes in EOD wave form and APD. Evidence presented here shows that changes in the passive membrane properties are unlikely to be responsible for the APD increase. The possibility is discussed that androgens act directly upon the electric organ, ultimately altering the ionic currents that produce the AP.
Action Potentials↗
Mercury and crematorium chimneys.
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Air Pollutants↗
Germ cell neoplasms of head and neck soft tissues: a pathologic spectrum of teratomatous and endodermal sinus tumors.
Germ-cell neoplasms, in particular teratomas with immature and mature somatic type tissues, are some of the most commonly found tumors in children. Approximately 5% of these neoplasms appear in one of several extracranial sites in the head and neck region. This study reports the clinical, pathologic and immunohistochemical findings in six germ-cell neoplasms occurring in the neck and facial areas. A mass was recognized at birth in five children, and the sixth patient was 2 1/2 years old at diagnosis. Four of the six neoplasms contained one or another element of endodermal sinus tumor; two of these had a mixed pattern of endodermal sinus tumor and teratoma. The other two cases were purely teratomas. The serum alpha-fetoprotein was known to be elevated in three children whose tumors had endodermal sinus elements; it returned to normal level in two of the children, but remained high in the one fatal case. Placental alkaline phosphatase and alpha-fetoprotein were demonstrated immunohistochemically in two of the three cases, with available tissue containing endodermal sinus tumor. Teratomatous metastases in ipsilateral cervical lymph nodes were found in one patient with a pure teratoma; that patient is disease-free one year after surgery. Only nine previous examples of endodermal sinus tumor have been reported in the head and neck region, exclusive of the central nervous system. There is one other case in the literature of a congenital cervicothyroidal teratoma with metastatic disease. These six neoplasms illustrate the clinical and pathologic spectrum in this nosologically homogeneous, but morphologically diverse, category of tumors.
Alkaline Phosphatase↗
The radiation dose to accompanying nurses, relatives and other patients in a nuclear medicine department waiting room.
The radiation dose to accompanying nurses, relatives and other patients in a nuclear medicine department waiting room was assessed at 5 min intervals by observing the seating arrangement. The total radiation dose to each person was calculated, using fixed values of dose rate per 100 MBq activity for radionuclides, and applying the inverse square law. Radioactive decay and attenuation effects due to intervening persons were also taken into account. The median radiation doses to accompanying nurses, relatives and other patients were 2.3, 2.0 and 0.2 microSv with maximum values of 17, 33 and 5 microSv respectively. In all cases, the radiation dose received by patients was less than 0.2% of the radiation dose resulting from their own investigation. Also, the maximum radiation dose received by an accompanying nurse or friend was less than 1% of their appropriate annual dose limit. Similar values were obtained with calculations based on a 15 min time interval. The radiation doses received by those in a nuclear medicine department waiting room are small, and separate waiting room facilities for radioactive patients are unnecessary.
Family↗
Infant feeding practices in Britain.
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Diet Surveys↗
Iron deficiency in children.
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Anemia, Hypochromic↗
Detection of feline calicivirus antigens in the joints of infected cats.
Twelve specific pathogen free cats were used to investigate the role of calicivirus in causing lameness. These were divided into two groups each of six cats; one group of cats had previously been vaccinated, the other had not. Three cats in each group were given live vaccine virus (F9 related) by the subcutaneous route and two in each group were challenged intranasally with field virus (A4), either four or seven days before euthanasia. The other two cats were controls. Virus was isolated from the oropharynx of five cats and the conjunctiva of a single cat. Four of these cats had been given the field virus and two the vaccine strain; the latter two cats had been previously immunised and had high circulating neutralising antibodies to calicivirus. No virus was isolated from the joints of any cat but immunofluorescence examination revealed viral antigens within the synovial macrophages of 14 joints from five cats, three having been given the field virus and two the vaccine virus seven days before euthanasia. Immunofluorescence also demonstrated the presence of immunoglobulin and complement within synovial macrophages suggesting that the virus was in the form of an immune complex. No lameness was reported in any cat and the synovial histological changes were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The effects of changes in heart rate and aortic systolic pressure on left ventricular myocardial oxygen consumption in lambs.
To determine whether changes in heart rate and aortic systolic pressure contribute equally to the determination of left ventricular myocardial oxygen consumption, we independently varied heart rate and pressure and compared the resultant oxygen consumption for similar rate-pressure products. In 6 young lambs which underwent atrioventricular node ablation, we varied heart rate by ventricular pacing at 250 beats/min, 300 beats/min, and 120 beats/min while aortic pressure remained stable and varied aortic systolic pressure by infusion of phenylephrine (to 132 +/- 15 mm Hg and 155 +/- 14 mm Hg) and by infusion of sodium nitroprusside (to 79 +/- 6 mm Hg) while heart rate was maintained stable at 200 beats/min. The 3 levels of change in aortic systolic pressure were chosen so that the ratepressure product during the pressure changes matched the rate-pressure product during the heart rate changes. We found that left ventricular myocardial oxygen consumption was the same at all 3 levels of the rate-pressure product whether heart rate was changed and pressure remained stable or pressure was changed and heart rate remained stable. Also, the correlation between oxygen consumption and the rate-pressure product was similar for both heart rate and pressure changes. During nitroprusside infusion at a fixed heart rate, oxygen extraction was significantly lower than during pacing at a heart rate of 120 beats/min when the rate-pressure product was comparable because of the direct vasodilatory effects of nitroprusside. We conclude that heart rate and aortic systolic pressure contribute equally to left ventricular myocardial oxygen consumption at the same rate-pressure product, even though there may be differences in myocardial blood flow and oxygen extraction.
Animals↗
Purification of the neurotensin receptor from bovine brain.
The neurotensin receptor protein, solubilized with digitonin/asolectin from bovine cerebral cortex membranes, was purified to apparent homogeneity by affinity chromatography using immobilized neurotensin. The product exhibits saturable and specific binding of [3,11-tyrosyl-3,5-3H]neurotensin with an apparent affinity (Kd = 5.5 nM) comparable to that measured in intact membranes and crude soluble extracts. The affinity-purified material, after reduction with 100 mM dithiothreitol, in denaturing gel electrophoresis showed a single polypeptide of Mr 72,000. Under nonreducing conditions the apparent Mr, however, was 50,000, suggesting the presence of intramolecular disulfide bonds. The purified neurotensin receptor was judged to be homogeneous, in that (i) only a single polypeptide was detectable; and (ii) the overall purification was 30,000-50,000-fold, giving a specific neurotensin-binding activity close to the theoretical maximum.
Animals↗