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Biomedical subjects

J Feldman

Publications and source records attributed to J Feldman.

At least 145 records · Page 8Linked to original sources

Baclofen prevents the increase of myocardial oxygen demand indexes evoked by the hypothalamic stimulation in rabbits.

The electrical stimulation of the paraventricular nucleus (PVN) of the hypothalamus in anaesthetized rabbits elicited important cardiovascular responses which were mainly characterized by increases in arterial pressure, dP/dtmax, and of the indexes of myocardial oxygen consumption, rate-pressure product (from 34 +/- 2 to 40 +/- 2 mmHg.bpm.10(-3) and triple product (from 102 +/- 12 to 162 +/- 19 mmHg2.s-1.bpm.10(-6). The hemodynamic alterations induced by PVN stimulation were similar to those observed during physical effort and stressful situations. Intracerebroventricular (0.1, 0.3 and 1 microgram.kg-1) or intravenous administration (1, 3 and 10 mg.kg-1) of baclofen, a selective GABAB receptor agonist, induced a dose-related decrease in the peak values of dP/dtmax and of the indexes of myocardial oxygen consumption (rate-pressure and triple products) during the electrical PVN stimulation. After 1 microgram.kg-1 baclofen (i.c.v.), the peak value of the triple product during PVN stimulation was 101 +/- 21 as compared to 149 +/- 15 before treatment. At the 10 mg.kg-1 dose (i.v.), the triple product during stimulation only reached 90 +/- 20 vs. 150 +/- 20 before treatment. These results suggested that a type B GABAergic transmission system is involved in the modulation of central control of the cardiac function. Drugs modulating this system could therefore be designed to blunt the myocardial oxygen demand increases.

Animals↗

Vitamin D3 binding activity during leukemic cell differentiation.

In this paper we report that differentiation of the human promyelocytic leukemia cell line, HL60, along the myelocytic pathway, induced by retinoic acid (RA), or monocytic pathway, induced by phorbol-myristate acetate (PMA) and gamma interferon (IFN), was accompanied by a significant decline in 1,25-dihydroxycholecalciferol (1,25(OH)2D3) binding (control: 30.3 +/- 3.0 fM/10(6) cells; RA treated: 6.8 + 2.5 fM/10(6) cells; PMA treated: 12.3 +/- 6.7 fM/10(6) cells and IFN treated: 16.0 +/- 5.0 fM/10(6) cells). When differentiation and proliferation were uncoupled, by incubation with IFN or by inhibition of proliferation by cell density saturation, 1,25(OH)2D3 binding was better related to differentiation than to proliferation. Additionally we have compared 1,25(OH)2D3 binding levels in blasts from acute lymphocytic leukemia (ALL) patients (25.4 +/- 18.1 fM/10(6) cells) and normal, mature lymphocytes (10.6 +/- 2.1 fM/10(6) cells). Receptor binding was significantly higher (p < 0.05) in the immature blasts. Our data suggest that 1,25(OH)2D3 receptor levels could be considered a marker of functional immaturity, in these cells.

Calcitriol↗

Are positive axillary nodes in breast cancer markers for incurable disease?

OBJECTIVE: This study was designed to determine if resection of positive regional nodes in patients with breast cancer provided a group of cured patients. SUMMARY BACKGROUND DATA: Previous studies of long-term follow-up of patients with breast cancer have demonstrated that 30% of patients with positive nodes may be alive at 10 or 20 years. Randomized, prospective studies have not shown a difference in survival between modified radical and total mastectomy. METHODS: The authors analyzed the statistical basis of randomized, prospective studies of breast cancer. Patients from University and Kings County Hospital with breast cancer were observed (n = 1024) and the 10-year survival curves were analyzed. Data from the Surveillance, Epidemiology, and End Results (SEER) program were evaluated to determine the prognosis of patients with positive-node breast cancer who survived 10 and 15 years. RESULTS: The authors found that no current randomized study of primary treatment of breast cancer has the power to determine the advantage of one treatment over another if the primary cancer is treated. Additionally, evaluation of the patients in this study demonstrated that those with regional disease usually had a recurrence by 7 years; however, at 10 years, 30% are still alive and have the same prognosis as patients with negative-node breast cancer. CONCLUSIONS: Regional breast cancer is a curable disease in some resected patients.

Adult↗

Acute alopecia: clue to thallium toxicity.

The combination of rapid, diffuse alopecia, and neurologic and gastrointestinal disturbance is pathognomonic for thallium toxicity. The hair mount, showing a tapered or bayonet anagen hair with black pigmentation at the base, may be highly diagnostic before the onset of alopecia. We saw a 10-year-old boy who suffered from thallium poisoning.

Abdominal Pain↗

Designing a connectionist network supercomputer.

This paper describes an effort at UC Berkeley and the International Computer Science Institute to develop a supercomputer for artificial neural network applications. Our perspective has been strongly influenced by earlier experiences with the construction and use of a simpler machine. In particular, we have observed Amdahl's Law in action in our designs and those of others. These observations inspire attention to many factors beyond fast multiply-accumulate arithmetic. We describe a number of these factors along with rough expressions for their influence and then give the applications targets, machine goals and the system architecture for the machine we are currently designing.

Algorithms↗

Oronasal reconstruction with local mucoperiosteal and free latissimus dorsi flaps.

We describe the use of maxillary sinus mucoperiosteum as a pedicled flap to reconstruct the floor of the nose following resection of cancer involving the palate, buccal mucosa, and mandible. Complete inferior turbinectomy allows access to the roof of the maxillary sinus to harvest the mucoperiosteum as a vascularized flap pedicled under the remaining middle turbinate. A free latissimus dorsi myocutaneous flap suspended from the floor of the orbit and nasal septum is then used to obliterate the maxillary sinus, reconstruct the palate, and support the floor of the nose. A reconstruction employing this combination of flaps is presented, including postoperative endoscopic intranasal photography and magnetic resonance imaging. Despite the elevated level of the floor of the nose and the absence of the inferior turbinates, rhinomanometry performed 3 months postoperatively demonstrates adequate nasal airflow with normal responses to nasal decongestants.

Aged↗

Arthritis and hypertension in patients with systemic lupus erythematosus.

OBJECTIVE: The purpose of this study was to test the hypothesis that patients with systemic lupus erythematosus (SLE) who have, as part of their disease, persistent rheumatoid-like arthritis are less likely to be hypertensive than are other patients with SLE. METHODS: A retrospective chart analysis of 662 patients with SLE seen in a university clinic was performed. RESULTS: Data analysis revealed that hypertension and persistent arthritis were inversely correlated, particularly in those patients without nephritis and particularly in black patients. CONCLUSION: We conclude that rheumatoid-like arthritis in patients with SLE is protective against hypertension, and speculate that this protection is conferred by a higher frequency of the DR4 allele.

Arthritis↗

Contribution of catecholaminergic neurons of the dorsomedial and ventrolateral medulla oblongata to the hypotensive effect of clonidine in spontaneously hypertensive rats: in vivo voltammetric studies.

OBJECTIVE: Our previous electrochemical studies in the normotensive Wistar-Kyoto (WKY) rat showed a positive correlation between the hypotensive effect of low doses of clonidine (2-10 micrograms/kg intravenously) and inhibition of the activity of catecholaminergic neurons within the brainstem, and that this action was mediated by imidazoline-preferring receptors. In the present study the possibility of a relationship between the centrally mediated hypotensive effect of clonidine and the metabolic activity of catecholaminergic neurons of the ventrolateral and dorsomedial medulla oblongata was investigated in pentobarbital-anaesthetized spontaneously hypertensive rats (SHR). DESIGN AND METHODS: Neuronal metabolic activity was monitored by in vivo electrochemistry in the nucleus reticularis lateralis region of the ventrolateral medulla and in the nucleus tractus solitarii region of the dorsomedial medulla oblongata. RESULTS: Hypotensive doses of intravenously administered clonidine (10 micrograms/kg) failed to inhibit the neuronal metabolic activity of the nucleus reticularis lateralis region; fivefold higher doses were required to inhibit these neurons. The low dose of clonidine (10 micrograms/kg) decreased the metabolic activity of the nucleus tractus solitarii region. Nevertheless, this effect did not appear to be correlated with a reduction in blood pressure and it was not attenuated by a prior central injection of idazoxan (5 nmol/kg intracisternally), which almost completely prevented the hypotensive and the neuronal inhibitory effects of clonidine in the nucleus reticularis lateralis region of the normotensive rat. CONCLUSION: Both the site and the mechanism of the central hypotensive action of clonidine in the SHR appear to be different from those in normotensive control WKY rats.

Animals↗

[Pharmacology of imidazoline receptors and cardiovascular regulation. Imidazoline receptors and blood pressure].

To explain the central hypotensive action of clonidine- and rilmenidine-type drugs, a recent hypothesis suggested the involvement of imidazoline preferring receptors (IPR) insensitive to catecholamines. Binding studies performed on neuronal membranes prepared from the human Nucleus Reticularis Lateralis area (NRL) showed that rilmenidine was twice as selective as clonidine for the medullary IPRs. Voltammetric experiments revealed that these substances preferentially inhibited the activity of catecholaminergic neurones within the NRL, privileged site for their hypotensive action, rather than the activity of the neurones of the Locus Coeruleus (LC) where these drugs induce their sedative effect. The mechanism of the inhibitory action of these compounds upon the neurones of the NRL definitely involved IPRs when the inhibition of the LC neurones involved classical alpha-2-adrenoceptors. These functional studies also showed that rilmenidine exhibited a selectivity twice as important as clonidine, the reference substance. Poly- and monoclonal anticlonidine antibodies cross-reacting only with imidazolines allowed to detect and immunoreactive substance in the human serum. The amounts of that substance thus measured were higher in some hypertensive patients than in normotensive subjects. The identity of that immunoreactive substance with "endazoline", the endogenous ligand of the IPRs, is presently analysed.

Animals↗

Imidazoline receptors. A new concept in central regulation of the arterial blood pressure.

Clonidine-like antihypertensive substances bind to nonadrenergic imidazoline specific sites within the nucleus reticularis lateralis (NRL), their medullary privileged site of action. Rilmenidine, a new central antihypertensive agent, was tested in the anesthetized rabbit. For the same hypotensive effect, cumulative doses given intracisternally proved 50 times more active than of those given systemically. Idazoxan, an alpha 2-adrenergic antagonist structurally related to the imidazolines, given centrally as pretreatment proved more potent in preventing the hypotensive effects than the same molar dose of yohimbine. When injected within the NRL area of the anesthetized rabbit, rilmenidine, like clonidine, always exhibited a hypotensive effect. The influence of clonidine and rilmenidine upon the NRL noradrenergic neurons involved in the blood pressure regulation, and upon those of the locus coeruleus (LC) involved in the sedative effect was studied by differential voltammetry. It was observed that rilmenidine was two times more selective than clonidine in inhibiting the NRL, as opposed to LC, neuronal activity. In addition, binding experiments of tritiated clonidine to human cortical and NRL membrane preparations showed that rilmenidine, as compared to clonidine, has a two to three times higher selectivity for the imidazoline receptors. In conclusion, we are now able to discriminate between the mechanism of the hypotensive effect of imidazoline-like drugs and that of their sedative action. Rilmenidine is the first example of an hypotensive drug more selective for imidazolin preferring receptors than for classical alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗

The French are different. French and American medicine in the context of AIDS.

Medicine has often been approached as a thing apart from culture, as a uniform Western science. Within the past 10 years, we have begun to recognize that medicine is a system of beliefs and practices intrinsically linked to its larger sociocultural context. Still, it is generally perceived as uniform across North America and Western Europe. My recent research on French and American medical perspectives on the acquired immunodeficiency syndrome (AIDS) challenges this view by exploring differences in the structure of health care, the physician-patient relationship, and the conceptualizations of disease, particularly AIDS. These differences are not specific to AIDS, but the disease serves to exemplify them and to act as a medium for expressing what makes French and American medicine distinct. Global epidemics such as AIDS require both international response and cross-cultural understanding.

Acquired Immunodeficiency Syndrome↗

Predictors of cocaine use in pregnancy.

Several hundred thousand infants are exposed to cocaine in utero every year in the United States. In an attempt to provide services for women abusing drugs, various programs have been proposed for prenatal drug testing. This study was conducted to assess the sensitivity, specificity, and predictive values of screening programs based on a variety of clinical and historical factors. Between October 1988 and March 1989, 1111 parturients who delivered at an inner-city hospital had urine samples and data collected. The urine, linked by code number to the data, which contained no identifiers, was tested anonymously for illicit drugs. We then assessed the associations of a variety of historical and clinical variables with positive toxicologies. An acknowledged history of drug use or a combination of no prenatal care and cigarette use provided the most valid prediction of cocaine use, with a 59.8% sensitivity, 97.5% specificity, 70% positive predictive value, and 94.9% negative predictive value for positive urine toxicologic examinations. The addition of clinical data such as low birth weight did not improve predictive values significantly. Although the use of easily available historical data allowed correct identification of 60% of parturients who used cocaine, no combination of factors could detect all users. If it is considered beneficial to identify all users at a given point, then urine toxicology screening would be more appropriate than sole reliance on patient history.

Cocaine↗

Selectivity of rilmenidine for the nucleus reticularis lateralis, a ventrolateral medullary structure containing imidazoline-preferring receptors.

Neuronal metabolic activity was studied by in vivo electrochemistry in two brain areas of the anesthetized rat: the nucleus reticularis lateralis (NRL) region of the ventrolateral medulla oblongata - site of the hypotensive action of clonidine-like imidazolines - and the locus coeruleus (LC), which is involved in the sedative effect of these drugs. Hypotensive doses of i.v. rilmenidine (0.3 and 1.5 mg/kg), which is structurally related to clonidine, induced a dose-related inhibition of the metabolic activity of catecholaminergic neurons in the NRL region whereas higher doses (50-fold) were required to inhibit the activity of the catecholaminergic neurons in the locus coeruleus. On the other hand azepexole, another centrally acting antihypertensive drug that is not structurally related to the imidazolines failed to inhibit the neuronal metabolic activity of the NRL region when administered i.v. in hypotensive doses (1 mg/kg). Taken together, these findings suggest that the central hypotensive action of clonidine-like drugs requires the imidazoline structure or pharmacologically compatible compounds like rilmenidine. Our results also show that rilmenidine is twice as selective as clonidine for the NRL region, which contains imidazoline-preferring receptors, compared with the LC, which contains mainly alpha 2-adrenoceptors. In conclusion, this study provides a functional confirmation of the dissociation between the therapeutic (hypotensive) and untoward (sedative) effects of rilmenidine.

Adrenergic alpha-Agonists↗

A preliminary study of excess risk of cardiovascular disease in the mothers of patients with rheumatoid arthritis.

Family histories were obtained from 123 patients with rheumatoid arthritis and 152 patients with other musculoskeletal complaints. The subjects were female patients aged 40 years or more seen at the Arthritis Clinic of the State University of New York Health Science Center at Brooklyn between October 1985 and February 1986. It was found that death due to heart disease or stroke was more common (adjusted p less than 0.02) in the mothers of patients with rheumatoid arthritis than in the mothers of control patients, and that heart disease was also reported to be more common in these mothers (adjusted p less than 0.005). Thus, it is possible that cardiovascular disease at least partially accounts for the previously noted (J Rheumatol 1986; 13:903-6) shorter life expectancy of the mothers of patients with rheumatoid arthritis.

Adult↗

The biologic and social consequences of perinatal cocaine use in an inner-city population: results of an anonymous cross-sectional study.

Cocaine use among pregnant women and reports of its adverse perinatal consequences have increased substantially over the past 10 years. However, most researchers have studied patients registered at drug treatment centers or have relied on voluntary participation by patients, either of which introduces the possibility of selection bias. To determine the frequency and consequences of prenatal cocaine use among an unselected inner-city obstetric population, we collected urine samples from parturient women at a municipal hospital and anonymously tested these specimens for metabolites of cocaine, marijuana, opiates, and methadone. Urine specimens, with linked obstetric data sheets, were available from a study population of 1111 patients, and pediatric data sheets were available for 846 mother-infant pairs. Cocaine metabolites were found in 11.5% of the urine samples collected, whereas metabolites of marijuana, opiates, and methadone, respectively, were present in 1.1%, 1.2%, and 0.3% of the specimens. Cocaine users were more likely than nonusers to have had no prenatal care (51% vs 8.8%; p less than 0.0001), to be American-born rather than Caribbean-born (71% vs 33%; p less than 0.001), and to have a higher parity (1.83 vs 1.14; p less than 0.0001). Infants of cocaine users had a lower mean gestational age (-0.93 weeks; p less than 0.01), a lower mean birth weight (2560 +/- 788 vs 3151 +/- 699 gm; p less than 0.001), and an increased probability of having an Apgar score of less than 7 at 5 minutes (12.5% vs 3.2%; p less than 0.0001). Multiple linear regression analysis that isolated confounding variables such as the presence or absence of prenatal care, maternal age and parity, and the use of cigarettes and alcohol did not substantially affect the differences described above. The effect of cigarette smoking on reducing fetal size was cumulative. In conclusion, cocaine is the most commonly used illicit drug among parturients in this community and is strongly associated with underutilization of prenatal care services. Infants of cocaine users are more likely to be preterm and depressed at birth and to have a low birth weight. Cocaine use, through the above-noted effects, increases the need for prenatal care while simultaneously decreasing the likelihood that it will be obtained.

Adult↗

Integration of form across saccadic eye movements.

To perceive a stable world, one must somehow be able to relate visual information from successive fixations. Little is known, however, about the nature of the integrative process. By using a task which requires the integration of spatial position information from different fixations, it is demonstrated that visual information from previous fixations is preserved in a world-centered representation which is precise enough to support judgements of geometric shape. It is also shown that successive views are aligned with respect to common visual features, indicating that visual stability may be normally accomplished by a visual matching strategy in combination with cancellation by an eye-position signal.

Attention↗