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Biomedical subjects

M Rogers

Publications and source records attributed to M Rogers.

At least 109 records · Page 6Linked to original sources

The successful implementation of pharmaceutical practice guidelines. Analysis of associated outcomes and cost savings. SWiPE Group. Systematic Withdrawal of Perioperative Expenses.

BACKGROUND: Although approximately 2,000 medical practice guidelines have been proposed, few have been successfully implemented and sustained. We hypothesized that we could develop and institute practice guidelines to promote more appropriate use of costly anesthetics, to generate and sustain widespread compliance from a large physician group, and to decrease costs without adversely affecting clinical outcomes. METHODS: A prospective before and after comparison study was performed at a tertiary care medical center. Clinical outcomes data and times indicative of perioperative patient flow were collected on the first of two sets of patients 1 month before discussion of practice guidelines. Practice guidelines were developed by the physicians and their associated care team for the intraoperative use of anesthetic drugs. A drug distribution process was developed to aid compliance. Clinical outcomes data and times indicative of perioperative patient flow were collected on the second set of patients 1 month after institution of practice guidelines. Hospital drug costs and adherence to guidelines were noted throughout the study period and for each of the following 9 months by querying the database of an automated anesthesia record keeper. RESULTS: A total of 1,744 patients were studied. Drug costs decreased from 56 dollars per case to 32 dollars per case as a result of adherence to practice guidelines. Perioperative patient flow was minimally affected. Time (mean +/- SD) from end of surgery to arrival in the post-anesthesia care unit (PACU) increased from 11 +/- 7 min before the authors instituted practice guidelines to 14 +/- 8 min after practice guidelines (P < 0.0001). Admission of inpatients to the PACU receiving monitored anesthesia care increased from 6.5 to 12.9% (P < 0.02). Perioperative patient flow and clinical outcomes were not otherwise adversely affected. Compliance and cost savings have been sustained. CONCLUSIONS: This study is an example of a successful physician-directed program to promote more appropriate utilization of health care resources. Cost savings were obtained without any substantial changes in clinical outcomes. Institution of similar practice guidelines should result in pharmaceutical savings in the range of 50% at tertiary care centers around the country, with a slightly smaller degree of savings expected at institutions with more ambulatory surgery.

Anesthesiology↗

The acoustic reflex in adults with histories of otitis media in childhood.

OBJECTIVE: To investigate the effects of a history of otitis media (OM) in childhood on the acoustic reflex threshold (ART) in young adults. DESIGN: Questionnaire responses on childhood ear and hearing problems were obtained from populations of university students. In Study 1, 31 students reporting histories of persistent childhood OM and 34 students with no known OM histories were identified. They received pure-tone audiometry, otomicroscopy, and measurement of ARTs for a 500 Hz pure tone. In Study 2, 20 students with OM histories and 20 students with no known OM histories received pure-tone audiometry, otomicroscopy, and measurement of ARTs for a broadband noise. RESULTS: Subjects with OM histories had higher ARTs than did subjects with no known OM histories. Multiple regression analyses showed that the main variables contributing to elevated reflex thresholds were raised hearing thresholds on the activator ear and tympanic membrane abnormalities on the probe ear. CONCLUSIONS: The elevated ARTs in adults with histories of childhood OM result from peripheral sequelae of OM. Further evidence is required to determine any functional significance of these raised reflex thresholds.

Acoustic Impedance Tests↗

Functional asymmetries in the movement kinematics of patients with Tourette's syndrome.

OBJECTIVES: This study adopted a concurrent task design and aimed to quantify the efficiency and smoothness of voluntary movement in Tourette's syndrome via the use of a graphics tablet which permits analysis of movement profiles. In particular, the aim was to ascertain whether a concurrent task (digit span) would affect the kinematics of goal directed movements, and whether patients with Tourette's syndrome would exhibit abnormal functional asymmetries compared with their matched controls. METHODS: Twelve patients with Tourette's syndrome and their matched controls performed 12 vertical zig zag movements, with both left and right hands (with and without the concurrent task), to large or small targets over long or short extents. RESULTS: With short strokes, controls showed the predicted right hand superiority in movement time more strongly than patients with Tourette's syndrome, who instead showed greater hand symmetry with short strokes. The right hand of controls was less force efficient with long strokes and more force efficient with short strokes, whereas either hand of patients with Tourette's syndrome was equally force efficient, irrespective of stroke length, with an overall performance profile similar to but better than that of the controls' left hand. The concurrent task, however, increased the force efficiency of the right hand in patients with Tourette's syndrome and the left hand in controls. CONCLUSIONS: Patients with Tourette's syndrome, compared with controls, were not impaired in the performance of fast, goal directed movements such as aiming at targets; they performed in certain respects better than controls. The findings clearly add to the growing literature on anomalous lateralisation in Tourette's syndrome, which may be explained by the recently reported loss of normal basal ganglia asymmetries in that disorder.

Adult↗

Calcium flux through predominantly independent purinergic ATP and nicotinic acetylcholine receptors.

Ligand-gated nicotinic acetylcholine receptors (nAChRs) and purinergic ATP receptors are often expressed in the same peripheral and central neurons, and ATP and acetylcholine (ACh) are stored together in some synaptic vesicles. Evidence has suggested that nAChRs and ATP receptors are not independent and that some agonists strongly cross-activate and desensitize both receptor types. Rat sympathetic neurons and nAChRs expressed in Xenopus oocytes were studied to determine the significance of the interactions caused by the two agonist types. Current amplitudes included with separate or combined applications of ATP and nicotine are > 90% additive and independent. Half of all neurons tested responded to either ATP or nicotine but not to both, indicating differences in the expression of the two receptors. In neurons that expressed both receptors types, the nAChRs were inhibited by the activity-dependent open-channel blocker chlorisondamine. If the purinergic and nicotinic receptors were significantly dependent and coactivated, then blocking the ion channels opened by a nicotinic agonist should diminish the current activated by a purinergic agonist. That result was not seen; rather, complete open-channel block of nAChRS with chlorisondamine did not significantly alter the amplitude or kinetics of ATP-induced currents in the same neurons. Finally, when cloned nAChR subunits were expressed in oocytes, ATP activated only very small currents compared with the current activated by Ach. For the 13 different nAChR subunit combinations that were studied, ATP (50-500 microM) activated a current that ranged from 0 to 4% of the size of the current activated by 100 microM ACh. In summary, we find that there is little cross reactivity, and nAChRs and purinergic ATP receptors are predominantly independent, acting with separable physiological characteristics. Therefore the quantitative Ca2+ flux could be separately determined for nAChRs and ATP receptors. The fraction of total current that is carried by Ca2+ was quantitatively determined by simultaneously measuring the whole cell current and the associated change in intracellular Ca2+ with fura-2. For sympathetic neurons bathed in 2.5 mM Ca2+ at a holding potential of -50 mV, Ca2+ carries 4.8 +/- 0.3% (mean +/- SE) of the inward current through neuronal nAChRs and 6.5 +/- 0.1% of the current through purinergic ATP receptors. In conclusion, activity-dependent Ca2+ influx through predominately independent populations of nAChRS and ATP neurons can produce different intracellular signals at purinergic and cholinergic synapses.

Animals↗

Tolerance of paclitaxel 3-hour infusion with and without granulocyte colony-stimulating factor on a biweekly schedule.

The object of this study was to define the toxicity and maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered on a biweekly schedule, without and with granulocyte colony-stimulating factor support. Eligible patients had a diagnosis of recurrent or metastatic carcinoma and had received no more than one prior chemotherapy regimen. Patients were treated with paclitaxel administered as a 3-hour infusion. Entry dose level was 150/mg/m2. Subsequent dose levels were 175, 200, and 225 mg/m2. Granulocyte colony-stimulating factor was added at the two highest dose levels beginning on day 4, until absolute neutrophil count was above 10 x 10(9)/L. Forty-six patients were entered. Up to 175 mg/m2 could be safely administered every 2 weeks. Previously treated patients experienced severe dose-limiting neutropenia at 200 mg/m2, and at 225 mg/m2 all patients experienced treatment delays due to grade 3/4 neutropenia. Dose intensity was maintained in all patients due to the addition of granulocyte colony-stimulating factor. Escalation to 250 mg/m2 does not appear desirable, due to neurotoxicity.

Adolescent↗

Identification and characterization of the protective hepatocyte erythrocyte protein 17 kDa gene of Plasmodium yoelii, homolog of Plasmodium falciparum exported protein 1.

We recently reported the discovery of a 17-kDa Plasmodium yoelii protein expressed in infected hepatocytes and erythrocytes, P. yoelii hepatocyte erythrocyte protein 17 (PyHEP17), and have demonstrated that this protein is a target of protective antibodies and T cells. Here, we report the identification and characterization of the gene encoding this protein and reveal that it is composed of two exons. Immunization of mice with PyHEP17 plasmid DNA induces antibodies, cytotoxic T lymphocytes, and protective immunity directed against the infected hepatocyte. Based on extensive sequence homology, expression pattern, and antigenic cross-reactivity, the Plasmodium falciparum homolog of PyHEP17 is identified as the protein known as exported protein-1 (PfExp-1), also called antigen 5.1, circumsporozoite related antigen, or QF116. Identity between PyHEP17 and PfExp-1 is 37% at the amino acid level (60/161 residues), mapping primarily to two regions within the second exon of 73% (16/22 residues) and 71% (25/35 residues) identity. On this basis, PfExp-1 is proposed as an important component of pre-erythrocytic human malaria vaccines.

Amino Acid Sequence↗

Cost-effectiveness of short-course zidovudine to prevent perinatal HIV type 1 infection in a sub-Saharan African Developing country setting.

OBJECTIVE: To evaluate the cost-effectiveness of a short-course zidovudine program to prevent perinatal transmission of human immunodeficiency virus (HIV) type 1 in sub-Saharan African country settings. DESIGN AND SETTING: Several clinical trials of short-course zidovudine during pregnancy for prevention of perinatal transmission of HIV are under way in developing countries in sub-Saharan Africa. A decision model was used to examine the cost-effectiveness of zidovudine programs in a hypothetical 1-year birth cohort in a sub-Saharan African setting from the perspective of the health care system and of society. A completed short course of zidovudine was assumed to reduce perinatal HIV transmission from 25% to 16.5%, approximately one half of the effect of the longer-course zidovudine. Estimates of program costs, lifetime HIV-related health care costs, and lost productivity costs were derived from the published literature and from preliminary data available from sites of planned clinical trials. Sensitivity analyses were conducted on all relevant parameters. MAIN OUTCOME MEASURES: Medical costs, lost productivity costs, program costs, cost savings, and incremental cost-effectiveness, expressed as cost per infant HIV infection prevented. RESULTS: The model estimated that a national zidovudine program in a setting with 12.5% HIV seroprevalence would reduce perinatal HIV incidence by 12% (4.9 infections per 1000 births). The costs to the health care system would be $3748 per infant HIV infection prevented. When productivity losses were included in the model, the cost decreases to $1115 per infant HIV infection prevented. The cost to implement a national zidovudine program including the cost of counseling, testing, and drugs, would be $2 million per 100,000 births or $20 per pregnant woman. In the base case, decreases in the cost of counseling and testing and increases in maternal HIV prevalence, zidovudine efficacy, and medical and lost productivity costs improved cost-effectiveness of the zidovudine program. CONCLUSIONS: Assuming demonstrable efficacy of short-course zidovudine prevention of perinatal HIV, a national perinatal HIV prevention program with zidovudine in most sub-Saharan African country settings would reduce the incidence of infant HIV infection and, in some settings, provide societal savings; however, substantial initial investment in such programs will be required. Where health care resources are limited, as in these regions, allocation of resources to a perinatal zidovudine program will need to be considered in the context of resources required for other pressing medical care needs.

Africa South of the Sahara↗

Noradrenaline inhibition of Ca2+ channels and secretion in single patch-clamped insulinoma cells.

Noradrenaline effects on voltage-operated calcium channels and exocytosis were studied, for the first time, in single patch-clamped RINm5F insulin-secreting cells. Noradrenaline, despite small and variable inhibition of calcium currents, strongly inhibited the increase in membrane capacitance (a measure of exocytosis) stimulated by both step depolarizations and the calcium ionophore, ionomycin. Noradrenaline similarly inhibited KCl- and ionomycin-induced [3H]serotonin release from RINm5F cell populations. Noradrenaline effects were mediated by PTX-sensitive G proteins. Noradrenaline inhibitory effects on secretion are, therefore, mainly exerted downstream from Ca2+ influx.

Animals↗

Auditory attentional deficits in patients with schizophrenia. A positron emission tomography study.

BACKGROUND: Patients with schizophrenia have frequently been found to perform poorly on tasks requiring selective attention, defined as the ability to focus attention on relevant information while simultaneously ignoring irrelevant stimuli. This study explores the brain mechanisms mediating attentional processing in patients with schizophrenia by measuring their regional cerebral blood flow (rCBF) with positron emission tomography using [15O] water as they performed tasks that differed systematically in attentional demand. METHODS: Ten schizophrenic patients (either neurolepticnaive or withdrawn from medication) (patient group) and 10 normal volunteers (control group) performed auditory target detection tasks. Different types of auditory stimuli (environmental sounds, meaningless speech sounds, and words) were presented either binaurally (ie, same sounds in both ears) or dichotically (simultaneous and different sounds in the 2 ears). In dichotic conditions, subjects were instructed to focus on either their left or right ear. RESULTS: Initial subtraction-based image analyses sought significant rCBF changes anywhere in the brain. Patients consistently had less significant activation than controls in right superotemporal gyrus (STG). Follow-up analyses used regions of interest traced on individual magnetic resonance images to precisely measure rCBF in STG. Unlike controls, patients had higher rCBF in the left STG during all activation conditions. CONCLUSIONS: The abnormal task-related rCBF asymmetry in STG of schizophrenic patients may indicate an isolated temporal lobe deficit, but it may also indicate abnormality in the thalamocortical circuitry mediating selective attention and/or in the brain systems that integrate auditory processing in the 2 hemispheres.

Adult↗

A positron emission tomography study of binaurally and dichotically presented stimuli: effects of level of language and directed attention.

Regional cerebral blood flow (rCBF) was measured using positron emission tomography with oxygen- 15 labeled water as 10 normal subjects listened to three types of auditory stimuli (environmental sounds, meaningless speech, and words) presented binaurally or dichotically. Binaurally presented environmental sounds and words caused similar bilateral rCBF increases in left and right superior temporal gyri. Dichotically presented stimuli (subjects attended to left or right ears) caused asymmetric activation in the temporal lobes, resulting from increased rCBF in temporal lobe regions contralateral to the attended ear and decreased rCBF in the opposite hemisphere. The results indicate that auditorily presented language and non-language stimuli activate similar temporal regions, that dichotic stimulation dramatically changes rCBF in temporal lobes, and that the change is due both to attentional mechanisms and to hemispheric specialization.

Adult↗

Hair shaft abnormalities: Part II.

The clinical and microscopic features are reviewed for trichothiodystrophy, woolly hair, uncombable hair, pili annulati, trichorrhexis invaginata and pseudomonilethrix.

Child↗

Vision impairment in Liverpool: prevalence and morbidity.

A database related to the activities of the Liverpool vision assessment team was used to identify all children with vision impairment aged 0-16 years, resident in Liverpool, UK, on 1 April 1995. Prevalence rates were calculated for all children with vision impairment, and separately for two groups: those with uncomplicated vision impairment, and those with additional pathology. Visual tract pathologies were tabulated and compared. Associated handicapping conditions were defined and the extent of multiple disability was investigated for all vision impaired children, for very low birthweight children, and for those with cortical visual impairment. Of 199 children with vision impairment, 69 (35%) had uncomplicated impairment and 130 (65%) had additional and usually multiple pathology. There were 111 boys (56%); the excess of males was not statistically significant. Prevalence rates per 10,000 population were 18.1 for all vision impairment, 6.3 for uncomplicated vision impairment, and 11.8 for vision impairment complicated by additional pathology. Genetically determined disease accounted for over half the cases of uncomplicated vision impairment. Among the 130 children with additional pathology, cortical visual impairment was the commonest visual tract finding, affecting 64 (49%); 86% had learning difficulties; 53% had cerebral palsy. Multidisability (two or more disabling conditions in addition to vision impairment) affected half the entire childhood vision impairment population. These data should assist health and education authorities to determine the size of the vision impairment problem and how it relates to other disabilities in childhood, and can facilitate resource allocation and service planning.

Adolescent↗