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Biomedical subjects

M Marcus

Publications and source records attributed to M Marcus.

At least 37 records · Page 2Linked to original sources

New trends in natural language processing: statistical natural language processing.

The field of natural language processing (NLP) has seen a dramatic shift in both research direction and methodology in the past several years. In the past, most work in computational linguistics tended to focus on purely symbolic methods. Recently, more and more work is shifting toward hybrid methods that combine new empirical corpus-based methods, including the use of probabilistic and information-theoretic techniques, with traditional symbolic methods. This work is made possible by the recent availability of linguistic databases that add rich linguistic annotation to corpora of natural language text. Already, these methods have led to a dramatic improvement in the performance of a variety of NLP systems with similar improvement likely in the coming years. This paper focuses on these trends, surveying in particular three areas of recent progress: part-of-speech tagging, stochastic parsing, and lexical semantics.

Algorithms

Ritanserin potentiates the stimulatory effects of raclopride on neuronal activity and dopamine release selectivity in the mesolimbic dopaminergic system.

The atypical profile of clozapine and some other new antipsychotic drugs has been attributed to a relatively selective effect on the mesolimbic dopaminergic system, as well as to their potent serotonin 5-HT2 receptor antagonism and high ratio of 5-HT2 to dopamine D2 receptor affinities. It is unclear, however, how concurrent 5-HT2 and D2 receptor antagonism specifically affects the mesoaccumbens and the mesocortical dopaminergic systems. The present study examined the effect of pretreatment with the 5-HT2 receptor antagonist, ritanserin, on changes in midbrain dopamine neuronal activity as well as in forebrain, extracellular concentrations of dopamine, induced by relatively low doses of the D2 receptor antagonist raclopride, utilizing in vivo extracellular single cell recording techniques and voltammetry in anesthetized rats, as well as microdialysis in freely moving rats. Raclopride alone (10-2560 microgram/kg, i.v.) induced a dose-dependent increase in three parameters of neuronal activity, i.e. burst firing, firing rate and variation coefficient, of midbrain DA neurons. This effect of raclopride was more pronounced in cells of the ventral tegmental area than in cells of the substantia nigra-zona compacta. Ritanserin alone (1.0 mg/kg, i.v.) also increased all three parameters of neuronal activity in dopamine cells of the ventral tegmental area, but only firing rate in the cells of the substantia nigra. Ritanserin pretreatment (30 min) significantly enhanced the stimulatory effects of low doses of raclopride (10-20 micrograms/kg, s.c.) increased extracellular concentrations of dopamine in the medial prefrontal cortex and the dorsolateral striatum by 75 and 110%, respectively, as measured by microdialysis. Ritanserin alone (1.5 mg/kg, s.c.) did not significantly affect cortical and striatal extracellular dopamine concentrations; however, pretreatment (40 min) with ritanserin elevated the raclopride-induced increase of dopamine concentrations in the medial prefrontal cortex of about 250%, but failed to affect the action of raclopride on striatal dopamine levels. Raclopride alone (10 and 320 micrograms/kg, i.v.) dose-dependently increased extracellular concentrations of dopamine in the nucleus accumbens and the dorsolateral striatum to about 500%, as determined by voltammetry. Ritanserin alone (1.0 mg/kg, i.v.) did not significantly affect the voltammetric dopamine signal in the nucleus accumbens or the dorsolateral striatum; however, ritanserin pretreatment (30 min) enhanced the raclopride-induced increase in accumbal but not striatal dopamine concentrations to about 1600%. The stimulatory effect of the combined ritanserin plus raclopride treatment on neuronal activity and DA release was more pronounced in the mesolimbic than the nigrostriatal dopaminergic system. The present data indicate that concurrent 5-HT2 and D2 receptor antagonism selectively affects the activity of the mesolimbic dopaminergic system. These findings provide an experimental basis for the notion that combined 5-HT2 and D2 receptor antagonism may underlie the limbic mode of action of at least some atypical antipsychotic drugs and consequently contribute to their unique therapeutic effects.

Animals

Mode of action of atypical neuroleptics in relation to the phencyclidine model of schizophrenia: role of 5-HT2 receptor and alpha 1-adrenoceptor antagonism [corrected].

In experiments in rats, by the use of single-cell recordings from midbrain dopamine (DA) neurons of the ventral tegmental area (VTA), the systemic administration of the schizophrenomimetic N-methyl-D-aspartate receptor antagonists phencyclidine (PCP) or dizocilpine (MK-801) caused an increased firing rate but reduced the variability of firing in VTA DA neurons. Burst firing was increased in cells predominantly located in the paranigral nucleus, a subdivision of the VTA largely projecting to the nucleus accumbens and other limbic regions, but reduced in DA cells predominantly located in the parabrachial pigmented nucleus, another subdivision of the VTA that projects largely to the prefrontal cortex (PFC). Thus, a severely impaired signal-to-noise ratio within the PFC DA projection was obtained, concomitant with an overactive mesolimbic DA system. The administration of high doses of ritanserin or atypical neuroleptics with prominent serotonin (5-hydroxytrypyamine) 5-HT2 receptor antagonist action, such as clozapine or amperozide, produced preferential activation of the PFC DA projection. In contrast, the selective D2 receptor antagonist raclopride caused a greater activation of the subcortical than cortical DA projections, as assessed by microdialysis experiments in vivo from our laboratory. Adding ritanserin treatment to raclopride markedly enhanced the raclopride-induced increase in DA levels in the medial PFC, an effect probably mediated by augmentation of the raclopride-induced increase in the burst firing of meso-cortical DA neurons, but failed to affect the action of raclopride on striatal DA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

Neuroepithelial bodies in relatively mature lungs: an investigation in prenatal and newborn lambs.

Lungs of fetal and neonatal lambs were found to contain small, inconspicuous and widely dispersed neuroepithelial bodies (NEB). Under the light microscope, NEB could only be identified with certainty by their positive immune reaction to antibodies against serotonin. At the ultrastructural level, a large number of dense-cored vesicles was found in the corpuscular cells of the NEB. However, the number of intracorpuscular nerve endings was small. We conclude from these findings that, in the lamb, NEB act primarily as local regulators of lung function and that their reflex-mediated actions may be of secondary importance. This may be related to the fact that lungs of lambs at birth are relatively mature compared to those of various other species. Increased maturation of lungs and a concomitant decreased risk of insufficient oxygenation might be associated with the presence of an oxygen-sensitive chemoreceptor with primarily local actions for prevention of hypoxia.

Animals

Managed care and dentistry: promises and problems.

At its inception in the mid-1950s, managed care held a number of promises for dental care providers and dental patients. Sometime during the development of managed care, however, many programs lost sight of the importance of provider equity. Using data from current programs, the authors contrast the original promises with the realities of managed care in dentistry.

Capitation Fee

Prazosin modulates the changes in firing pattern and transmitter release induced by raclopride in the mesolimbic, but not in the nigrostriatal dopaminergic system.

Most antipsychotic drugs are, in addition to being dopamine (DA) D2 receptor antagonists, also relatively potent alpha 1 adrenoceptor antagonists. Here, we have studied the effects of the selective DA D2 receptor antagonist raclopride, alone and in combination with the selective alpha 1 adrenoceptor antagonist, prazosin, on midbrain DA neurons utilizing extracellular single cell recording techniques. As a reference compound, haloperidol (0.05-1.6 mg/kg, i.v.), a potent antagonist at both DA D2 receptors and alpha 1 adrenoceptors, was included in the electrophysiological part of the study. In addition, in vivo voltammetry was used to measure extracellular DA concentrations in the nucleus accumbens (NAC) and the dorsolateral striatum (STR) in anesthetized, pargyline pretreated rats treated with the above drugs. Raclopride (10-5120 micrograms/kg, i.v.) induced a dose dependent increase in firing rate of DA neurons in the ventral tegmental area (VTA), that was significant already at 10 micrograms/kg, and in the substantia nigra-zone compacta (SN-ZC), that reached significance at 2560 micrograms/kg. Burst firing of DA neurons was also increased in the VTA at 40 micrograms/kg, as well as in the SN-ZC at 640 micrograms/kg. A low dose of raclopride (80 micrograms/kg, cumulated dose) induced a significant increase in extracellular DA concentrations in NAC to 490% and in STR to 220%. A high dose of raclopride (2560 micrograms/kg, cumulated dose) induced a 930% increase in extracellular DA concentrations in NAC, but only a 280% increase in STR. These data demonstrate that raclopride exerts a relatively selective action on mesolimbic DA neurons. Prazosin (0.3 mg/kg, i.v.) decreased burst firing of VTA, but not SN-ZC DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Factors associated with the use of screening mammography in a primary care setting.

Despite consensus recommendations the use of screening mammography remains low. We examined physician and patient related variables associated with requests to undergo screening mammography in a primary care setting, in order to assess current barriers to screening mammography at the level of the physician-patient interaction. A sample of 261 women over the age of 50, whose primary care was provided by resident physicians in a large, urban, academic medical center were examined. Data concerning patients and physicians demographic and clinical characteristics were abstracted. The data were analyzed by Chi-square and stepwise logistic regression. Forty-five percent of the patients were offered screening mammography within the study year and 53% were offered mammography over the preceding two years. Variables significantly associated with a request for screening included a previous history of breast disease (p < .001) and the severity of the patient's overall medical condition. Patients with an overall medical condition rated as mild were more likely to be requested to undergo screening than patients rated as moderately or severely ill (p < .01). Patients with higher educational levels were also more likely to be offered screening (P = .06). First year postgraduate (PGY 1) physicians requested more mammograms than PGY 2 or PGY 3 physicians (P < .05). A multivariable model utilizing logistic regression confirmed the association of the significant variables above with screening requests. Physicians were more likely to request mammography in patients at higher risk for developing breast cancer and less likely to request it in patients who had co-morbid illness. Increasing physician understanding of the importance and benefits of mammography and further investigation of strategies to ensure physician compliance with mammography recommendations are necessary to increase utilization.

Aged

Year-long weight loss treatment for obese patients with type II diabetes: does including an intermittent very-low-calorie diet improve outcome?

PURPOSE: To evaluate a year-long behavioral weight control program, used with and without an intermittent very-low-calorie diet (VLCD) in the treatment of type II diabetes mellitus. PATIENTS AND METHODS: Subjects (n = 93) were randomly assigned to 50-week treatment programs that used either a balanced low-calorie diet (LCD) of 1,000 to 1,000 kilocalories (kcal) per day throughout or included 2 12-week periods of a VLCD of 400 to 500 kcal per day alternating with the balanced LCD. Weight, glycemic control, blood pressure, and lipids were assessed at baseline, at the end of the year-long treatment, and at 2-year follow-up. RESULTS: Subjects in the VLCD program lost significantly more weight than did LCD subjects at the end of the 50-week program (14.2 kg versus 10.5 kg; P = 0.057) and remained off diabetes medication longer (P < 0.05). These benefits of the VLCD were due primarily to the first 12 weeks of the diet; the second diet maintained, but did not increase, these effects. Subjects in both groups experienced marked improvements in glycemic control and cardiovascular risk factors over the year-long program, but attendance declined in the latter weeks of treatment and weight was regained. There was also marked recidivism in both groups in the year following treatment. CONCLUSIONS: The intermittent VLCD improved weight loss and glycemic control, but these effects were quite modest and do not appear to justify the clinical use of an intermittent VLCD. Moreover, lengthening treatment to a full year did not prevent relapse. Thus, further research is needed to develop a successful approach to long-term weight control.

Adult

An estrogen receptor genetic polymorphism and the risk of primary and secondary recurrent spontaneous abortion.

OBJECTIVE: A case-control study was undertaken to assess the association between an estrogen receptor gene variant and the risk of recurrent spontaneous abortions. STUDY DESIGN: The frequency of the estrogen receptor gene variant in blood lymphocyte deoxyribonucleic acid and other selected maternal characteristics was compared among 60 primary recurrent aborters, 61 secondary recurrent aborters, and 43 women who had had at least two live births but no spontaneous abortions. RESULTS: No association was evident between the estrogen receptor gene variant and the risk of either primary or secondary recurrent abortion. There were data suggesting that primary recurrent aborters in particular were more likely to report a family history of recurrent abortion and a family history of breast cancer. CONCLUSIONS: These findings indicate that the estrogen receptor polymorphism is not a genetic marker for recurrent spontaneous abortions. Therefore, as suggested by previous investigations, this polymorphism appears to be a marker for breast cancer risk only among the subgroups who have had a history of repeated abortions.

Abortion, Habitual

Measuring oral health status: theoretical and methodological challenges.

Development of oral health status indexes poses a set of theoretical and methodological challenges. Although the amount of work done on oral health indexes is far less that that done on general health indexes, to date those developed share many of the same theorectical assumptions. For the most part they have shared the dominant biomedical paradigm and the underlying theory of illness. These theories significantly influence both the instruments developed to measure oral health and the methods of measurement adopted. More recently alternative, holistic theories of illness have been proposed and there has been a shift from instruments focused on the provider to those focused on the patient and a move from objective to subjective measures of oral health. Furthermore the relationship between oral health and general health has received insufficient attention. The paper examines the relationship between the theories of illness, methods of measurement, and oral health indexes and suggests that other holistic, patient centered, paradigms, using qualitative methods, should also be considered in the construction or oral health indexes.

Attitude to Health

Rhabdomyosarcoma: invading the orbit in an adult.

Sites in the head and neck region are among the most frequent locations of rhabdomyosarcoma (RMS) in patients younger than 15 years. However, comparable neoplasms in adults are very uncommon. We present a case report of a 27-year-old man who was diagnosed as having RMS. RMS rarely presents in the head and neck of adults, but should be considered in the differential diagnosis of a small cell neoplasm in patients during the third and fourth decades of life.

Adult

A reproductive hazards research agenda for the 1990s. Research Needs Working Group.

There is substantial scientific and public concern about the potential effects of occupational and environmental toxicants on reproductive health. These effects include impaired functioning of the reproductive systems of men and women as well as a broad spectrum of developmental problems expressed in offspring. Research on reproduction and development is among the most complex undertakings in biomedical research. This complexity is due in part to the intricate biology of reproduction, the multiple targets involved (male, female, and offspring), the uncertainties in extrapolating from animal models to humans, and the problems involved in accurately characterizing exposures and outcomes in epidemiologic investigations. However, given the relatively brief history of research into toxicant-induced reproductive health effects, we have made enormous strides in our knowledge over the past decade. In particular, recent advances in reproductive biology and biotechnology and in the development of biological markers of exposure, effect, and susceptibility are greatly enhancing our ability to study cause-effect relationships. In this paper, the Research Needs Working Group proposes ways to apply existing knowledge to better protect reproductive health and suggests directions for future research. Fulfilling this challenging agenda will require responsible cooperation by labor, industry, government, individual citizens, and the scientific community. Further research and collaboration are essential to both prevent adverse reproductive and developmental outcomes and to formulate a sound scientific basis for policy making.

Communication

Quality assurance in medicine: a dental audit system.

Two principal components of a quality assurance system for dental plans are described, using a case report to illustrate the methodology. Criteria of acceptable quality of patient care for general practice were developed first. Then plan, practice and patient profiles, derived from claims or encounter data, were used to identify the nature and extent of aberrant patterns which were uncovered. Based on analysis of the profiles, site visits were made to a targeted sample of practices and selected patient dental records were evaluated for various levels of the process of care. Categories were rated as either acceptable or unacceptable. Principal dentists were debriefed on the findings and a report including corrective action plans prepared for the responsible agency. Follow-up to monitor compliance is planned. Although aberrant profiles do not necessarily mean that care is unacceptable, the findings from the record review confirmed the concerns raised by the data analysis.

Capitation Fee

Urinary follicle-stimulating hormone as a biological marker of ovarian toxicity.

Reproductive senescence has not been adequately explored as a possible end point for assessing toxicity to the reproductive system. We propose that urinary FSH be used as a biologic marker of ovarian function in women. A urinary marker would facilitate the incorporation of this measure into epidemiologic studies of reproductive toxicity. Although there is some evidence that FSH in serum is a good biologic marker of ovarian reserve, the relationship between serum FSH and urinary FSH has not been adequately explored. We found that urinary FSH and serum FSH were closely correlated in 50 consecutive women seen in clinical practice.

Adult