Biomedical subjects
J Feldman
Publications and source records attributed to J Feldman.
Role of imidazoline receptors in cardiovascular regulation.
The involvement of nonadrenergic imidazoline specific receptors in the central control of the vasomotor tone and in the mechanism of action of drugs bearing an imidazoline structure, or analogs, is now well documented. Imidazoline-specific binding sites were found in many tissues and species. Moreover, until now, it is only in the brainstem that such binding sites are associated with a function: the hypotensive effect of imidazoline-like drugs. Rilmenidine, which is an oxazoline structurally related to the reference imidazolines, exerts a central hypotensive effect of central origin involving imidazoline receptors. The selectivity of rilmenidine for the imidazoline receptors compared to alpha 2-adrenergic receptors could explain the low incidence of sedative side effects observed with this antihypertensive drug. A specific anti-imidazoline radioimmunoassay allowed us to detect the presence of an immunoreactive imidazoline-like substance in human sera. High levels of this immunoreactive substance are associated with high blood pressure in 20-30% of the hypertensive patients. This observation indicates that high levels of this immunoreactive substance in the serum can be associated with some kinds of primary hypertension. The cause-and-effect relation between these 2 phenomena has not yet been determined. This substance is in process of purification; it could be a candidate to be an endogenous ligand of the imidazoline receptors.
Sexually transmitted diseases, sexual behavior, and cocaine use in inner-city women.
The prevalence of untreated sexually transmitted diseases (STDs) was assessed in a cohort of 372 sexually active inner-city women (92% black, 49% US-born) with no history of injection drug use who were recruited in Brooklyn, New York, in 1990 and 1991. The presence of STDs was assessed via culture, serologic analyses, and medical history. Sexual and drug-use histories were obtained, as was a urine sample for toxicologic analysis. Thirty-five percent of the women had at least one STD (27% Trichomonas vaginalis, 6.8% Chlamydia trachomatis, 5.2% syphilis, 2.4% human immunodeficiency virus (HIV), and 1.4% Neisseria gonorrhoeae). US-born women were more likely than foreign-born (96% Caribbean) women to have an STD (50% vs. 22%; p < 0.001). Among US-born women, 61% of crack and/or cocaine users had an STD as opposed to 34% of non-users (OR = 2.9, 95% CI 1.6-5.5). Recent crack cocaine use was the strongest predictor of syphilis infection (OR = 12.8, p = 0.019), and was reported by each of the seven HIV-positive women. This study, based on a large sample with laboratory confirmation of both STDs and drug use, documents that women who use crack cocaine are at substantially higher risk of contracting an STD than other women. STD/HIV prevention programs in inner cities should target US-born women, particularly crack cocaine users.
Molecular cloning of a putative vesicular transporter for acetylcholine.
Classical neurotransmitters such as acetylcholine (ACh) require transport into synaptic vesicles for regulated exocytotic release. The Caenorhabditis elegans gene unc-17 encodes a protein with homology to mammalian transporters that concentrate monoamine neurotransmitters into synaptic vesicles. Mutations in unc-17 protect against organophosphorus toxicity, indicating a role in cholinergic neurotransmission. Using the relationship of unc-17 to the vesicular amine transporters, we first isolated a related sequence from the electric ray Torpedo californica [Torpedo vesicular ACh transporter (TorVAChT)] that is expressed by the electric lobe but not by peripheral tissues. Using the relationship of the Torpedo sequence to unc-17, we then isolated the cDNA for a rat homologue (rVAChT). Northern blot analysis shows expression of these sequences in the basal forebrain, basal ganglia, and spinal cord but not cerebellum or peripheral tissues. In situ hybridization shows expression of rVAChT mRNA in all cholinergic cell groups, including those in the basal forebrain, brainstem, and spinal cord that previously have been shown to express choline acetyltransferase mRNA. The human VAChT gene also localizes to chromosome 10 near the gene for choline acetyltransferase. Taken together, these observations support a role for rVAChT in vesicular ACh transport and indicate its potential as a novel marker for cholinergic neurons.
[Nosocomial acquisition of Clostridium difficile infections].
Clostridium difficile (CD) is associated with diarrhea in hospital patients receiving antibiotic therapy and may be nosocomially acquired. An outbreak of CD diarrhea was observed among elderly patients in acute hospital and geriatric rehabilitation wards. All but 1 patient presenting with diarrhea had a toxin-positive stool culture. Of patients with CD toxin-positive cultures, 4 died, 5 recovered completely and 1 became a chronic carrier. Effective preventive measures are needed to reduce nosocomial acquisition of CD.
Analysis of multiple primary cancers in a single institution.
Records of 120 patients with two and 16 with three primary cancers were evaluated. There were 49 males and 71 females among the double primaries with ages ranging from 27-102 years (average 68 years at the time of fist cancer). Of 35 breast cancer patients 16 new primaries developed in the opposite breast and other sites including four colon, three lung, and three endometrium. Of 20 colon cancer patients second primaries occurred in 11 sites most commonly colon (four) and lung (three). The frequency of second primaries may be skewed by the fact that patients with lethal cancers did not live long enough to develop them. This is borne out by the fact that 74 of the 120 patients were alive at the time of the study, implying a highly favorable group of patients. The interval between primaries was longer in females than males (P < 0.05) and this difference disappeared when breast and endometrial cancer were eliminated. When age was evaluated as a factor younger patients appeared to have a longer interval between primaries (P = 0.24) and this became significant for breast patients under age 55 years (91 months vs. 36 months) (P < 0.05). The stage of the second breast primary bore no relationship to the interval between primaries.
Hepatitis C in patients with porphyria cutanea tarda.
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Forgetting sexual trauma: what does it mean when 38% forget?
L. M. Williams (1994) has shown that many women who were sexually abused as children do not report the abuse when questioned 2 decades later. These findings do not support certain freely made claims about memory, but they do support other claims. The findings do not provide cogent support for the claim that a long stream of childhood sexual traumas is routinely banished from conscious awareness and then can be reliably recovered later. The findings do support the claim that many children can forget about a sexually abusive experience from their past. Extreme claims such as "if you were raped, you'd remember" are disproven by these findings.
Biological false-positive syphilis test results for women infected with human immunodeficiency virus.
Regardless of the nontreponemal test used for the screening and diagnosis of syphilis, biological false-positive results (BFPs) are documented in 1%-2% of all cases. An association between BFPs and human immunodeficiency virus (HIV) infection in men has been suggested. We conducted a cohort study to determine whether a similar association between HIV seropositivity and BFPs exists for women. Among 156 HIV-seropositive women, 9 (5.8%) had a BFP for syphilis. Among 633 HIV-seronegative women, only 1 (0.2%) had a BFP. When the 25 HIV-seropositive patients and 55 HIV-seronegative patients with reactive rapid plasma reagin tests and microhemagglutination assays for antibodies to Treponema pallidum were excluded from the calculations, 6.9% and 0.2% of HIV-seropositive and HIV-seronegative women, respectively, had BFPs (P < .001; odds ratio, 39.45; 95% confidence interval, 6.4-879.0). An association was found between injection drug use and BFPs for the population of HIV-infected women but did not entirely account for the differences between this group and the HIV-seronegative group.
Medullary hypotensive effect of endothelin1 in anaesthetized animals.
In anaesthetized animals, systemic injection of ET1 at doses from 3 to 100 ng.kg-1 provoked only a transient hypotensive effect. At 300 ng.kg-1 we observed the classical biphasic effect, consisting of a transient lowering of the arterial pressure followed by a long-lasting hypertensive effect. Direct injection of the peptide into the vertebral artery of anaesthetized animals only affected arterial pressure (AP) when the blood-brain barrier was permeabilised. Under these conditions, a dose-dependent decrease in AP was observed, which was not associated with a significant effect on the heart rate. Micro-injections of the peptide in the medullary nucleus reticularis lateralis area (NRL), a medullary vasopressive centre, at doses of 30 to 60 ng.kg-1 led to a significant reduction in mean arterial pressure (MAP) (17 +/- 4% and 36.5 +/- 6%) respectively without a significant change in heart rate. These effects lasted less than 2 hours. These results suggest a possible role of ET1 as a neuromodulator involved in the central regulation of vasomotor tone, in the NRL region.
Prevention by NMDA receptor antagonists of the centrally-evoked increases of cardiac inotropic responses in rabbits.
1. The purpose of this study was to investigate further the role of the excitatory amino acid (EAA) system of neurotransmission, particularly of the NMDA receptor, in the central regulation of cardiac function. 2. Electrical stimulation of the paraventricular nucleus of the hypothalamus (PVN) in pentobarbitone anaesthetized rabbits induced a cardiovascular response mainly characterized by a positive inotropic effect, hypertension and a marked increase in the myocardial oxygen demand index. 3. The intracerebroventricular (i.c.v.) or intravenous (i.v.) injection of different EAA antagonists acting on different sites of the NMDA receptor/channel complex dose-dependently blunted the excitatory cardiovascular effects of PVN stimulation. 4. 5,7 Dichlorokynurenic acid was used as a specific glycine site antagonist and 2-amino-5-phosphonovaleric acid was used to block the agonist recognition site; ketamine was used as a channel blocker site antagonist and ifenprodil as a blocker of the polyamine binding site. 5. 5,7 Dichlorokynurenic acid (125 and 250 micrograms kg-1, i.c.v.) virtually abolished the cardiovascular responses, inducing only haemodynamic depression at the highest dose used. 2-Amino-5-phosphonovaleric acid (0.1 to 1.0 mg kg-1, i.c.v.) elicited a reduction of the peak values observed during PVN stimulation which was accompanied by a decrease of the basal cardiovascular parameters. Ketamine (2.5 and 10 mg kg-1) and ifenprodil (1 mg kg-1), injected intravenously, blocked the haemodynamic response induced by PVN stimulation without marked reduction of the basal haemodynamics. 6. It is concluded that glutamate neurotransmission is not only involved in vasomotor tone control but also in the central control of cardiac function and can therefore modulate the myocardial oxygen demand.
Maternal drinking during pregnancy: attention and short-term memory in 14-year-old offspring--a longitudinal prospective study.
A large and compelling experimental literature has documented the adverse impact of prenatal alcohol exposure on the developing brain of the offspring. This is the first report of adolescent attention/memory performance and its relationship with prenatal alcohol exposure in a population-based, longitudinal, prospective study (n = 462) involving substantial covariate control and "blind" examiners. Prenatal alcohol exposure was significantly related to attention/memory deficits in a dose-dependent fashion. A latent variable reflecting 13 measures of maternal drinking was correlated 0.26 with a latent variable representing 52 scores from 6 tests measuring various components of attention and short-term memory performance. The number of drinks/occasion was the strongest alcohol predictor. Fluctuating attentional states, problems with response inhibition, and spatial learning showed the strongest association with prenatal alcohol exposure. A latent variable reflecting the pattern of attention/memory deficits observed at 14 years correlated 0.67 with a composite pattern of deficits previously detected on neurobehavioral tests administered during the first 7 years of life. The 14-year attention/memory deficits observed in the present study appear to be the adolescent sequelae of deficits observed earlier in development. As is usual in such studies, not all exposed offspring showed deficits.
Carboxyhemoglobin levels in patients with cocaine-related chest pain.
Carboxyhemoglobin (COHb) levels were measured in patients who came to an emergency department complaining of acute chest pain. For subjects not receiving prior oxygen therapy, those with cocaine-related chest pain (n = 10) had a higher mean COHb level than a comparison group (n = 28) with nonischemic chest pain (4.50 +/- 2.40 vs 2.73 +/- 0.66; p < 0.05). Four of the seven (57 percent) who smoked crack had COHb levels greater than 4.5 percent, while only one of six (17 percent) smokers of only tobacco had such a level. These findings suggest an additional mechanism, the formation of COHb, which could aggravate cocaine-induced cardiotoxicity.
Breast biopsy rate and positivity in Rhode Island.
Breast biopsy is a common procedure for which few age-specific, population-based data are available. We identified all women who underwent breast biopsy in Rhode Island in 1989 by reviewing the specimen logs at each of 13 pathology laboratories. Among 425,000 women aged 15-97 years, 2685 underwent breast biopsy, for an overall rate of 6/1000. The rate increased with age, peaking among 45- to 54-year-olds and then declining in women over 75. Among those biopsied, 726 were diagnosed with breast cancer, for an overall biopsy positivity of 27%. In contrast to rate, positivity increased steadily with age. These results are within the range of estimates produced by smaller group studies.
Creating a MEDPAR (Medicare provider analysis and review) analog to the RUG-III (Resource Utilization Groups, Version III) classification system.
As Medicare payments for post-acute institutional care continue to rise sharply, policy interest in the clinical characteristics of beneficiaries admitted to nursing homes and their variation across facilities has stimulated research into case mix. Measures of Medicare skilled nursing facility (SNF) case mix are important in relating payments to the care requirements of residents. The Resource Utilization Groups, Version III (RUG-III) classification system uses a new minimum data set that is not currently available nationally. In preparation for a multi-State demonstration, we needed to simulate at least the first-level splits at the national, State, and facility level. Therefore, we developed proxy measures using comparable data available on the National Claims History files. The analog is an easily programmed measure of the acuity/severity of beneficiaries' conditions across a Medicare Part A SNF stay in 75 percent of the SNF providers. This can be a method for estimating changes in case mix over the years, and differences across provider types and States.
Animal behavior case of the month. Aggression toward a neonatal foal by its dam.
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A controlled study of cognitive and language function in school-aged HIV-infected children.
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Idiopathic CD4+ T-lymphocytopenia.
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