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Biomedical subjects

J Feldman

Publications and source records attributed to J Feldman.

At least 163 records · Page 9Linked to original sources
PubMed1991

An imidazoline-specific mechanism for the hypotensive effect of clonidine: a study with yohimbine and idazoxan.

Our previous in vivo electrochemical studies in the normotensive rat have shown that there was a positive correlation between the hypotensive effect of low doses of clonidine (8-40 nmol/kg i.v.) and the inhibition of the metabolic activity of catecholaminergic neurons within the nucleus reticularis region in the brain stem. Higher doses of the drug (200 nmol/kg i.v.) were required to decrease the metabolic activity in the locus ceruleus, which is involved in the sedative effect of clonidine. To investigate further the pharmacological mechanism involved in the hypotensive effect of imidazolines, low doses of antagonists were injected centrally in the cisterna magna (5 nmol/kg intracisternal): idazoxan, an imidazoline that labels nonadrenergic imidazoline-preferring sites and yohimbine, which is a classical alpha-2 adrenergic antagonist. Our results show that idazoxan very potently antagonizes both the hypotensive effect of clonidine and neuronal inhibition on the nucleus reticularis lateralis region but not in the locus ceruleus. The opposite effect is observed with yohimbine, i.e., neither the hypotensive effect nor the neuronal inhibition produced by clonidine on the nucleus reticularis lateralis region were affected but it prevented the inhibitory effect of clonidine on locus ceruleus neuronal metabolic activity. In conclusion, we confirm the hypothesis that the hypotensive action of imidazoline is due to an interaction of these substances with imidazoline-preferring receptors in the ventrolateral medulla oblongata whereas its sedative effect is related to an action on alpha-2 adrenoceptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Laparoscopic pelvic lymphadenectomy.

Eleven male patients with pelvic malignancy underwent laparoscopic lymphadenectomy for staging of their tumors. The technique allowed removal of pelvic lymph nodes in all 11 patients and metastatic disease was found in five cases, resulting in a change of recommended therapy. The technique was via a three-port exposure, although a fourth suprapubic port was occasionally used for additional retraction. A bladder laceration, which was repaired laparoscopically, was the only intraoperative complication. A pelvic hematoma was the only significant postoperative complication. Laparoscopic pelvic lymphadenectomy appears to offer a less morbid staging for those patients with a high likelihood of nodal metastasis. Laparoscopic detection of positive pelvic lymph nodes may alter the management of genitourinary malignancy and improve overall patient care.

Acid Phosphatase↗
PubMed1991

Passive smoking alters lipid profiles in adolescents.

Although cigarette smoking is associated with elevation of plasma lipid levels and changes in lipoprotein distribution, it is not known whether passive smoking is associated with an alteration in lipid profiles. The relation between plasma cotinine, a marker of exposure to tobacco smoke, and lipid profiles was studied in healthy adolescents from a suburban New York high school district who were undergoing preparticipation sports physicals. Forty-four percent of the adolescents reported that one or both parents currently smoked. Eleven percent of the adolescents had plasma cotinine concentrations greater than or equal to 2.5 ng/mL, the level considered indicative of exposure. Adolescents with two smoking parents had significantly higher plasma cotinine concentrations after adjustment for other factors than adolescents whose parents did not smoke. Plasma cotinine concentration greater than or equal to 2.5 ng/mL was associated with an 8.9% greater ratio of total cholesterol to high-density lipoprotein cholesterol (P less than .003) and a 6.8% lower high-density lipoprotein cholesterol (P less than .03). These results suggest that passive smoking, like active smoking, leads to alterations in lipid profiles predictive of an increased risk of atherosclerosis.

Adolescent↗
PubMed1991

Arthritis and nephritis in patients with systemic lupus erythematosus.

Previous publications suggest that in patients with systemic lupus erythematosus (SLE), rheumatoid factor (RF) may be "protective" against nephritis. In our study of 662 patients with SLE, we found that persistent, rheumatoid-like arthritis showed a much stronger inverse correlation with nephritis than RF. Of 186 such patients, 59 developed clinically evident nephritis (32%) compared to 263 of the other 476 patients (55%) (p less than 10(-7). RF showed only a weak inverse relationship to nephritis (p = 0.064). We conclude that the presence of persistent rheumatoid-like arthritis in patients with SLE identifies a clinical subset of patients who are less likely to develop nephritis than those with no arthralgia, no objective arthritis or only episodic arthritis. We hypothesize that such patients represent a genetically determined subset among patients with SLE and that perhaps they are more likely to bear the HLA-DR4 allele.

Adolescent↗
PubMed1990

Sexually transmitted diseases and human immunodeficiency virus infection among women with pelvic inflammatory disease.

Both human immunodeficiency virus infections and pelvic inflammatory diseases are sexually acquired illnesses of great consequence to women. This study was undertaken to determine if women hospitalized with pelvic inflammatory disease, in a community endemic for human immunodeficiency virus, were at high risk to be infected with human immunodeficiency virus and if human immunodeficiency virus infections altered their hospital course. One hundred ten women hospitalized with pelvic inflammatory disease in Brooklyn (in a hospital in which 2% of parturients are human immunodeficiency virus seropositive) agreed to human immunodeficiency virus testing; 15 (13.6%) were found to be seropositive. Seropositive women were significantly more likely to have an admission white blood cell count less than 10,000/mm3 (p = 0.001). Human immunodeficiency virus seropositivity was not associated with a higher frequency of other sexually transmitted diseases although there was a trend toward more cases of syphilis among human immunodeficiency virus-infected women. Similarly, although there was no significant difference in rates of operative intervention (26.6% among seropositive and 8.4% among seronegative; p = 0.058), there was a trend toward more surgery among those who were human immunodeficiency virus infected. Women hospitalized with pelvic inflammatory disease, in a community endemic for human immunodeficiency virus, are at high risk for human immunodeficiency virus infection. More research is needed to verify a trend toward more refractory infections among human immunodeficiency virus-infected women.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The relationship of cocaine use to syphilis and human immunodeficiency virus infections among inner city parturient women.

To study the relationship of cocaine use to syphilis and human immunodeficiency virus infections a blinded urine and serum survey was performed among parturient women at an inner city hospital. Discarded urine samples of 1206 parturient women were saved and given code numbers that were also assigned to data sheets containing nonidentifying information, including prenatal care status and syphilis serologic results. In the latter part of the study blood remaining after syphilis serologic tests were performed (n = 480) were tested for human immunodeficiency virus antibodies. Overall 12.9% of urine samples had cocaine derivatives, 1.4% opiates, 1.5% marijuana, 0.0% benzodiazepine, and 0.3% methadone. The prevalence of positive rapid plasma reagin tests was 18.7% among patients with positive urine toxicologic tests for cocaine and 2.41% for patients with negative urine tests (odds ratio = 9.3, 95% confidence interval 5.2 to 16.5, p less than 0.001). Fluorescent treponemal antibodies were also significantly more frequent among patients with positive urine samples. Four of 53 (7.6%) patients with positive urine toxicologic screens were human immunodeficiency virus antibody positive compared with six of 427 (1.4%) women with negative screens (odds ratio = 5.7, 95% confidence interval = 1.4 to 21.5, p = 0.019). Cocaine patients with positive cocaine screens and with syphilis or human immunodeficiency virus had prenatal care in 6 of 21 (28.6%) and 0 of 4 (0%) cases, respectively, while patients with negative cocaine screens and syphilis or human immunodeficiency virus had prenatal care in 13 of 18 (72.2%) and 5 of 6 (83.3%) cases, respectively (p = 0.010 and p = 0.048). Cocaine use appears to be associated with both the acquisition of human immunodeficiency virus and syphilis and the failure of infected individuals to utilize prenatal services.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Blunted growth hormone responses to clonidine in adolescent girls with early anorexia nervosa. Evidence for an early hypothalamic defect.

We studied growth hormone (GH) levels in 14 adolescents with anorexia nervosa (AN), 12-20 years of age. All had amenorrhea and the duration of symptoms ranged from 2-24 months. There was no difference in unstimulated GH between the girls with AN and endocrinologically normal girls. However, the GH response to the alpha-adrenergic agent clonidine was blunted (less than 10 ng/ml) in 11 of 14 girls with AN. Our results of a normal basal GH level and blunted response to stimulation is in contrast to some reports of high basal GH levels and an exaggerated response to pituitary stimulation although it agrees with other studies. Our patient population was younger and at an earlier stage of the disease (12 with symptoms for less than 1 year) than the AN patients previously reported to have elevated GH secretion. In view of studies that report an elevated GH response to growth hormone releasing factor, our results suggest that the AN patient's abnormalities in GH secretion may result from an abnormal hypothalamic response to adrenergic stimuli. This hypothalamic abnormality might also contribute to the growth failure seen in adolescent girls with AN.

Adolescent↗
PubMed1990

Evidence for the involvement of imidazoline receptors in the central hypotensive effect of rilmenidine in the rabbit.

1. Rilmenidine has recently been introduced as a new centrally-acting antihypertensive agent. We examined its cardiovascular effects after intracerebral injection to anaesthetized rabbits. Cumulative doses of rilmenidine injected intracisternally (1 to 300 micrograms kg-1) led to dose-dependent decreases in arterial blood pressure and heart rate. The effective doses of rilmenidine were lower when injected centrally than when injected intravenously. 2. Pretreatment with the same dose of yohimbine or idazoxan shifted the rilmenidine dose-response curves for its hypotensive and bradycardic effects to the right. Idazoxan, which has an imidazoline structure, proved to be a more active antagonist than yohimbine of rilmenidine centrally-mediated cardiovascular effects. 3. The dose-response curve for the central hypotensive effect of rilmenidine was also shifted to the right after pretreatment with a bovine brain extract. This extract contains the endogenous ligand of the imidazoline-preferring receptors which is not a catecholamine. 4. Rilmenidine, like clonidine, proved to be active when micro-injected into the rabbit nucleus reticularis lateralis region. 5. In conclusion, rilmenidine exhibited in the rabbit a central hypotensive effect which originated in the same area as where clonidine acts. Specific imidazoline-preferring receptors appear to be involved in this hypotensive effect.

Animals↗
PubMed1990

[Selectivity of a new antihypertensive agent, rilmenidine, for imidazoline receptors in the human brain].

The involvement of the central nervous system in the global hypotensive effect of rilménidine (R) was already suspected after experiments on cats and dogs. Indeed, the injection of this drug in the vertebral artery provoked a decrease in the arterial blood pressure in these two species. Recently, we showed that intracisternal injections of cumulative doses (1 to 300 micrograms/kg) in anaesthetized rabbits significantly lowered the blood pressure. In that protocol the efficient dose 20% was 1.5 micrograms/kg when it was 70 micrograms/kg for intravenous injections. The hypotension was always associated with bradycardia. Thus we confirmed that the drop in the arterial blood pressure induced by R was, at least partially, due to a central inhibition of the vasomotor tone. When we pretreated anaesthetized rabbits, always by intracisternal injections, with identical doses of yohimbine or idazoxan (5 nmoles/kg), we observed that idazoxan prevented much more the hypotensive effects of R than yohimbine. This study demonstrated that R whose chemical structure is close to that of imidazolines was much better antagonized by a substance with an imidazoline-like structure than by a classical alpha 2-antagonist. These results were confirmed by binding studies realized with human brain membranes. Tritiated clonidine was bound to cortical membrane preparations, containing mainly alpha 2-adrenoceptors, as well as to medullary membrane preparations, containing mainly imidazoline receptors. We observed that R selectivity for the medullary imidazoline preferring receptors was 2.5 times higher than that of the reference substance, clonidine. So, it seems that the central hypotensive effect of R might be related to its interaction with imidazoline specific receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1990

Syphilis among parturients at an inner city hospital: association with cocaine use and implications for congenital syphilis rates.

The frequency of positive cord blood rapid plasma reagin (RPR) tests among newborns at an inner city hospital and associations with maternal cocaine use, prenatal care, and adequacy of syphilis therapy were retrospectively assessed. The incidence of positive cord blood RPRs increased from 1.1% of all live births in 1985 to 3.4% in 1988. In 1987, 98 babies were born with positive cord blood RPRs; 86 of their charts were available for review. Four infants had false positive RPRs, and one patient delivered twins, leaving 81 mothers who could be evaluated. Almost 37% of these patients had had no prenatal care. More than 55% had inadequate or not therapy for syphilis. Of these, only 17.4% had prenatal care. Slightly more than 40% of patients acknowledged using drugs during pregnancy, 87.9% of whom used cocaine. Among the patients who used drugs, 75.8% received no prenatal care, in contrast to 10.4% of mothers who did not use drugs (p less than 0.001). It appears that drug use, particularly use of cocaine, is associated with low levels of utilization of prenatal services and inadequate therapy for syphilis. This may lead to increased risk of congenital syphilis in newborns.

Cocaine↗
PubMed1989

New concepts on the central regulation of blood pressure. Alpha 2-adrenoceptors and "imidazoline receptors".

The most usual hypothesis to explain the central hypotensive effect of clonidine-like substances was to admit that these drugs stimulated alpha 2-adrenoceptors within the brainstem. Now it has been demonstrated that neither the endogenous ligand to the alpha-adrenoceptors, noradrenaline, nor any other catecholamine or phenylethylamine was hypotensive in the medullary nucleus reticularis lateralis, where all imidazolines proved to be such. Recently, a membrane receptor population sensitive to clonidine and insensitive to catecholamines was described within the nucleus reticularis lateralis; this subgroup of receptors represented 20 to 30 percent of the [3H]clonidine binding sites in the bovine nucleus reticularis lateralis and 100 percent within the human nucleus reticularis lateralis region. Thus, the existence of such imidazoline specific receptors was clearly established and the endogenous ligand for those receptors, which is neither a catecholamine nor likely a peptide, is under processing for purification. Therefore, it appeared that the hypotensive effect of substances with an imidazoline or imidazoline-like structure might be due to their action within medullary receptors specific for this endogenous ligand temporarily named "clonidine displacing substance." Rilmenidine, structurally close to imidazolines, also interfered with these receptors. The central component of its hypotensive effect was recently confirmed in rabbits, where its central cardiovascular effects were antagonized by "the clonidine displacing substance." Although exhibiting a lower affinity than the reference substance for these receptors, rilmenidine might have a higher selectivity, thus explaining its restricted side effects. A structure-activity study with this molecule would bring a confirmation to these first observations.

Adrenergic alpha-Agonists↗
PubMed1989

Rilmenidine selectivity for imidazoline receptors in human brain.

The selectivity of three centrally acting antihypertensive agents for the medullary imidazoline-preferring receptors (IPR) versus cortical alpha-adrenoceptors was investigated in human brain. [3H]Clonidine binding was studied in various membrane preparations. Competition experiments were performed. Cortical membrane preparations were used as they mainly contained classical alpha-adrenoceptors whereas medullary membrane preparations from the nucleus reticularis lateralis contained only IPR insensitive to catecholamines. Rilmenidine, a new antihypertensive agent, appeared 2.5 and 3.5 times more selective than clonidine and guanfacine, respectively, for medullary IPR sites than for cortical alpha-adrenoceptors, thus providing a possible explanation for the low sedative effects of this new molecule.

Adrenergic alpha-Agonists↗
PubMed1989

The imidazoline preferring receptor: binding studies in bovine, rat and human brainstem.

The binding of [3H]clonidine to brainstem membrane preparations was studied in an attempt to characterize imidazoline-sensitive, catecholamine-insensitive receptors. Human samples and samples from two animal species were used. [3H]Clonidine binding was always saturable, reversible and specific with a KD value of 6-7 nM. The Bmax values were 45.5 +/- 5.5, 145 +/- 34 and 65 +/- 33 fmol/mg protein in the whole rat medulla oblongata, the nucleus reticularis lateralis region of bovine and that of human, respectively. In the whole rat brainstem we could not demonstrate the presence of [3H]clonidine binding sites that were insensitive to catecholamines. In bovine and human nucleus reticularis lateralis (NRL) preparations, the amount of specifically bound labelled clonidine that was not displaced by an excess of (-)-norepinephrine was 25 and 100%, respectively. Substances that had a structure similar to that of clonidine were able to compete with [3H]clonidine binding within the human NRL. Cirazoline was the most potent to inhibit [3H]clonidine binding although yohimbine was also able to displace binding in the human NRL but with lower apparent affinity. Competition assays with idazoxan stereoisomers clearly showed that this binding was stereospecific. Therefore the human NRL region provides the first model of an homogenous population of imidazoline-preferring, non-alpha-adrenergic membrane receptors.

Animals↗
PubMed1989

Screening with Doppler velocimetry in labor.

Doppler flow velocimetry was performed on 273 nonselected patients in labor. All patients were at least 2 cm dilated and 80% effaced (58% greater than 4 cm) and were delivered of infants within 24 hours. Fetal heart rate tracing performed at the same time was read by another observer and compared with Doppler flow velocity measurements (systolic/diastolic ratio, pulsatility index). A significant correlation was noted (r = 0.234, p less than 0.001) between the two modalities. Both fetal heart rate tracings and umbilical flow velocity measurements were correlated with fetal outcome. Significant associations were noted between the umbilical systolic/diastolic ratio and fetal distress. 5-minute Apgar scores, the need for intubation independent of gestational age, and umbilical arterial cord pH and base excess. It appears that the information obtained from flow velocimetry had additional benefits compared with that of fetal heart rate tracings alone.

Adult↗
PubMed1989

Internal mammary artery bypass grafting: influence on recurrent angina and survival in 2,100 patients.

Internal mammary artery (IMA) bypass grafting to the anterior descending coronary artery was performed in 2,100 patients between January 1978 and July 1986. The average number of additional saphenous vein grafts (SVGs) per patient was 1.8. During the same period, 1,753 patients underwent coronary artery bypass grafting using an SVG (average number of grafts per patient, 3.2). The average patient age was similar: 62.3 years for IMA grafts and 64.7 years for SVGs. Men constituted two thirds of each group. Left ventricular function was impaired (ejection fraction less than 45%) in 1,071 (51%) of IMA grafts and 847 (48.3%) of SVGs. Other aggregate risk factors, ie, elevated blood pressure, diabetes mellitus, previous myocardial infarction, and congestive heart failure, were similar in each group. Operative results and postoperative mortality of the IMA and SVG patients were comparable. However, the long-term probability of cumulative survival and occlusion-free survival were significantly greater and the probability of recurrent angina and reoperative coronary artery bypass grafting were significantly less in IMA graft patients (p less than 0.015). The relative risk of occlusion in an SVG was 4 to 5 times greater than that of the IMA graft. These data indicate that a patent IMA graft to the anterior descending coronary artery protects against recurrent angina and death from cardiac-related causes, and that the IMA should be the conduit of choice.

Adult↗
PubMed1989

Dyslipoproteinemia in murine systemic lupus erythematosus.

Dyslipoproteinemia, a feature of systemic lupus erythematosus may contribute to premature atherosclerosis. In order to develop an experimental model for this dyslipoproteinemia we measured plasma concentrations of lipoproteins in juvenile NZB/W (lupus) and NZB/B (control) mice. Additionally to evaluate the effects of a diet rich in n - 3 fatty acids we measured lipoprotein concentrations in mice on normal or menhaden oil-enriched diets. The lupus mice had elevated triglycerides compared to the controls, similar to that seen in human SLE patients (161 +/- 31 vs 113 +/- 13 mg/dl, P less than 0.003). In contrast, the menhaden oil diet fed NZB/W mice had triglycerides similar to the NZB/B control fed group. In the NZB/W murine SLE model, dyslipoproteinemia is an early sign of disease as has been shown in man, therefore this model will be useful in elucidating the mechanism of dyslipoproteinemia in SLE.

Animals↗
PubMed1989

Religiosity, schizotypal thinking, and schizophrenia.

The relationship between religiosity and the incidence of schizotypal thinking was investigated in a normal sample and in acute and chronic schizophrenic samples. The Rust Inventory of Schizotypal Cognitions was administered to measure schizotypal thinking, and two religiosity measures were developed. Religiosity had a significantly negative relationship with schizotypal thinking in normal subjects, while in schizophrenic patients the relationship was positive and significantly different. It is suggested that the process of existential growth of awareness in the normal development of religious belief, which is thought to be associated with schizotypal thinking, may have proceeded differently in persons suffering from schizophrenia.

Adult↗