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Biomedical subjects

M Brodsky

Publications and source records attributed to M Brodsky.

At least 19 recordsLinked to original sources

Surface and subsurface irrigation with effluents of different qualities and presence of Cryptosporidium oocysts in soil and on crops.

A large variety of human pathogens are excreted in wastewater including bacteria, viruses, protozoan cysts and helminth eggs. In raw sewage, human pathogens reach high numbers, thereafter decreasing successively at each treatment step. However, the final effluents still contain a large fraction of these pathogens that may pose a serious public health. Among the various crops irrigated with effluents, vegetables are the most vulnerable to contamination. Vegetables, usually eaten raw (uncooked) or with rich dressings (causing regrowth of some pathogenic bacteria) pose the main threat to humans. The importance of microbiological and parasitological criteria for reused water has been repeatedly emphasized. Some microbiological recommendations based on epidemiological data have been established for untreated wastewater, there is still a need to define the criteria for effluent quality required for unrestricted crop irrigation. This paper presents a field study comparison of two irrigation methods: surface and subsurface of field crops (mainly vineyard) and follow-up of Cryptosporidium oocysts in soil at different depths (0 to 90 cm). Oocysts were isolated at all depths without a clear pattern of distribution (0 to 640 oocysts/g). In addition different vegetables irrigated with different effluent qualities were tested for the presence of Cryptosporidium oocysts and Giardia cysts. The highest prevalence of oocysts was found on zucchini that has a sticky and hairy outer surface (80 to 10,000 oocysts/0.5 kg).

Agriculture↗

Localization in artificial disorder: two coupled quantum dots

Using single electron capacitance spectroscopy, we study electron additions in quantum dots containing two potential minima separated by a shallow barrier. Analysis of the addition spectra in the magnetic field allows us to distinguish between electrons delocalized over the entire dot and those localized in either of the potential minima. We demonstrate that a high magnetic field abruptly splits up a low-density droplet into two smaller fragments, each residing in a potential minimum. An unexplained cancellation of electron repulsion between electrons in these fragments gives rise to paired electron additions.

Journal Article↗

Allergic conjunctivitis and contact lenses: experience with olopatadine hydrochloride 0.1% therapy.

OBJECTIVE: The efficacy of Patanol, a topically applied anti-allergic agent, was evaluated in a group of patients with allergic conjunctivitis due to contact lens wear (GROUP I) and a group comprised of seasonal allergic conjunctivitis patients, vernal conjunctivitis patients and atopic keratoconjunctivitis patients (GROUP II). METHODS: One drop of Patanol was administered to each eye twice daily. Signs and symptoms were assessed 7, 14, and 28 days after initiation of drug therapy. RESULTS: Itching/burning, tearing, hyperemia and papillary reaction were reduced to scores of 0/1 (absent/mild) in 85%, 90%, 81% and 62%, respectively, of GROUP I patients at Day 28. The allergic conditions in GROUP II patients also improved with Patanol treatment. Itching/burning, tearing, hyperemia and papillary reactions were absent/mild in 60%, 76%, 96% and 90%, respectively, of these patients at Day 28. CONCLUSION: Patanol treatment effectively and rapidly alleviated the signs and symptoms of allergic conjunctivitis due to contact lens wear as well as vernal conjunctivitis, atopic keratoconjunctivitis and the common seasonal allergic conjunctivitis. Patanol allowed allergic patients to be more comfortable while permitting them to continue using contact lenses.

Acute Disease↗

Localization-delocalization transition in quantum dots

Single-electron capacitance spectroscopy precisely measures the energies required to add individual electrons to a quantum dot. The spatial extent of electronic wave functions is probed by investigating the dependence of these energies on changes in the dot confining potential. For low electron densities, electrons occupy distinct spatial sites localized within the dot. At higher densities, the electrons become delocalized, and all wave functions are spread over the full dot area. Near the delocalization transition, the last remaining localized states exist at the perimeter of the dot. Unexpectedly, these electrons appear to bind with electrons in the dot center.

Journal Article↗

Mu and delta opioid receptor analgesia, binding density, and mRNA levels in mice selectively bred for high and low analgesia.

The present study examined mu and delta opioid analgesia, receptor binding, and receptor mRNA levels in lines of mice from two selective breeding projects of relevance to opioid analgesia. Large differences were observed in the analgesic potency of [d-Ala2, NMPhe4, Gly-ol]enkephalin (DAMGO), [d-Pen2,5]enkephalin (DPDPE), and [d-Ala2]deltorphin II (DELT), selective mu, delta1, and delta2 opioid receptor agonists, respectively, in mice selectively bred for high (HA) and low (LA) swim stress-induced analgesia (SIA). HAR and LAR mice, selectively bred for high and low levorphanol analgesia, respectively, display equally large differences in their analgesic sensitivity to DAMGO, modest differences in sensitivity to DPDPE, and no differences in sensitivity to DELT. These sizable genotypic differences in analgesic potency were accompanied by HA/LA and HAR/LAR differences in whole-brain homogenate [3H]DPDPE and/or [3H]DELT, but paradoxically not [3H]DAMGO, binding. Solution hybridization of mRNA extracts encoding mu (MOR-1) or delta (DOR-1) opioid receptors indicated some regional differences in gene expression between high and low lines. Surprisingly, differences in these in vitro markers were often in the direction of LAR>HAR. The present data indicate that selection for either SSIA or levorphanol analgesia produces differential effects on mu and delta opioid analgesia that are accompanied by alterations on in vitro assays, the significance of which remains to be determined. The data are discussed with regard to the utility of in vitro biological markers and genetic models of analgesia.

Analgesics, Opioid↗

Initial clinical experience with a fully automatic in-hospital external cardioverter defibrillator.

Sudden cardiac death due to ventricular tachyarrhythmia remains a significant problem in the in-hospital setting. Although the probability of survival is closely correlated with the rapidity of a response by qualified personnel, response times can be prolonged, even in specialized care units. In an effort to decrease response time, a fully automatic external cardioverter defibrillator was recently devised. This device was evaluated in the in-hospital setting to assess safety and efficacy. A total of 79 patients were studied in a multicenter trial. Patients were monitored with fully functional devices in the electrophysiology laboratory (51 patients) and in the cardiac care unit (28 patients). Performance of the device was assessed by comparing automatic responses to any sustained change in cardiac rhythm, either spontaneous or induced, to a retrospective review of stored ECG data and programmed parameters. During a total duration of 964 hours of monitoring, there were 99 episodes of sustained tachycardia. Therapy was appropriately delivered or advised in all episodes. Therapy was advised in one episode of supraventricular tachycardia. There were no episodes of inappropriate therapy delivery. There were no complications or adverse events. The device performed with a sensitivity of 100% and specificity of 98.8% with an average response time of 22 seconds. In conclusion, this automatic external defibrillator was safe, effective, and functioned as designed. Significant improvement in response time to life-threatening ventricular tachyarrhythmia in the in-hospital setting would be expected if this technology was widely adopted.

Adult↗

Molecular mechanisms of developmental disorders.

One of the central tenets of developmental psychopathology is the belief that we can learn more about normal functioning through the study of psychopathology and arrive at a better understanding of pathological conditions through investigations of normal behavior. Advances in knowledge from one area will inform us regarding mechanisms at work in the other. A similar perspective is the driving force behind recent scientific advances in our understanding of certain developmental disorders. In this paper, molecular findings for four developmental disorders are reviewed: Prader-Willi syndrome, fragile X syndrome, Williams syndrome, and lissencephaly. These disorders were chosen for discussion because putative genes for each of them have been isolated. The ways in which mutations within these genes disrupt normal cognitive and behavioral functioning are discussed. Although considerable progress has been achieved in understanding the genetic mechanisms for these illnesses, much more research is needed to identify the environmental and genetic factors that interact to contribute to the expression of the more complex behavioral disorders.

Brain Damage, Chronic↗

Comparison of clinical characteristics and frequency of implantable defibrillator use between randomized patients in the Antiarrhythmics Vs Implantable Defibrillators (AVID) trial and nonrandomized registry patients.

In the Antiarrhythmics Vs Implantable Defibrillators (AVID) trial, all patients who meet the study entry criteria are followed in a registry. During the period between June 1993 and June 1995, of 1,117 patients who were enrolled in the registry and met the study entry criteria, 476 were randomized to receive either implantable cardioverter-defibrillators (ICDs) or drug therapy (amiodarone or sotalol), and 641 patients were not randomized for a variety of reasons including: patient refusal (42%); physician refusal (43%); concerns about ability to maintain follow-up over several years (10%), and others (6%). There were no significant differences between the 476 randomized and 641 nonrandomized patients with regard to clinical characteristics, left ventricular function, history of congestive heart failure, medical history, and previous cardiac procedures performed before the index event, except that randomized patients were slightly older (65 vs 62 years) and had a slightly higher prevalence of coronary artery disease and previous myocardial infarction. The index event and location of the index event were not significantly different between the 2 groups. Although 14% of registry patients received neither ICD nor antiarrhythmic drug therapy, ICDs were no more frequently used in the registry patient than antiarrhythmic drugs (45% for ICD vs 42% for drugs). Thus, randomized AVID patients have very similar clinical characteristics, cardiac history, and presenting arrhythmias as to nonrandomized eligible patients. Therefore, the results of the AVID trial may be generalized for all patients with AVID-eligible arrhythmias.

Adolescent↗

mirror encodes a novel PBX-class homeoprotein that functions in the definition of the dorsal-ventral border in the Drosophila eye.

The Drosophila eye is composed of dorsal and ventral mirror-image fields of opposite chiral forms of ommatidia. The boundary between these fields is known as the equator. We describe a novel gene, mirror (mrr), which is expressed in the dorsal half of the eye and plays a key role in forming the equator. Ectopic equators can be generated by juxtaposing mrr expressing and nonexpressing cells, and the path of the normal equator can be altered by changing the domain of mrr expression. These observations suggest that mrr is a key component in defining the dorsal-ventral boundary of tissue polarity in the eye. In addition, loss of mrr function leads to embryonic lethality and segmental defects, and its expression pattern suggests that it may also act to define segmental borders. Mirror is a member of the class of homeoproteins defined by the human proto-oncogene PBX1. mrr is similar to the Iroquois genes ara and caup and is located adjacent to them in this recently described homeotic cluster.

Amino Acid Sequence↗

A randomized trial of low osmolar ionic versus nonionic contrast media in patients with myocardial infarction or unstable angina undergoing percutaneous transluminal coronary angioplasty.

OBJECTIVES: The purpose of this study was to determine prospectively whether the differences in anticoagulant and antiplatelet effects of ionic and nonionic contrast media after angiographic or clinical outcomes in patients with unstable ischemic syndromes undergoing percutaneous transluminal coronary angioplasty. BACKGROUND: The interaction of platelets and thrombin with the endothelium of injured vessels contributes to thrombosis and restenosis after coronary angioplasty. Case reports and retrospective observations have reported an increased risk of thrombosis with the use of nonionic contrast media. METHODS: A total of 211 patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty were randomized to receive nonionic or ionic low osmolar contrast media. Coronary angiograms were assessed by a technician blinded to the study contrast media, and clinical events were monitored by an independent nurse for 1 month. RESULTS: Patients receiving the ionic media were significantly less likely to experience decreased blood flow during the procedure (8.1% vs. 17.8%, p = 0.04). After the angioplasty, residual stenosis, vessel patency, the incidence of moderate to large thrombi and use of adjunctive thrombolytic therapy were similar between the two groups. However, patients receiving ionic media had fewer recurrent ischemic events requiring repeat catheterization (3.0% vs. 11.4%, p = 0.02) and repeat angioplasty during the initial hospital stay (1.0% vs. 5.8%, p = 0.06). One month after angioplasty, patients receiving ionic contrast media reported significantly fewer symptoms of any angina (8.5 vs. 20.0%, p = 0.04) or of angina at rest (1.4% vs. 11.8%, p = 0.01) and a reduced need for subsequent bypass surgery (0% vs. 5.9%, p = 0.04), compared with patients receiving the nonionic media. CONCLUSIONS: These findings demonstrate that in patients with unstable ischemic syndromes undergoing coronary angioplasty, the use of ionic low osmolar contrast media reduces the risk of ischemic complications acutely and at 1 month after the procedure. Therefore, low osmolar ionic contrast media should be strongly considered when performing interventions in patients with unstable angina or myocardial infarction.

Angina, Unstable↗

The effect of the irreversible mu-opioid receptor antagonist clocinnamox on morphine potency, receptor binding and receptor mRNA.

In these experiments, the effect of the irreversible mu-opioid receptor antagonist clocinnamox on the potency of morphine, opioid receptor binding and mu-opioid receptor mRNA was examined. Mice were injected with clocinnamox (0.32-12.8 mg/kg) and the analgesic potency of morphine was examined 24 h later. Clocinnamox produced a dose-dependent decrease in the potency of morphine; and at the higher dose of clocinnamox the maximal analgesic effect was not observed following doses of morphine in excess of 500 mg/kg s.c. In saturation binding studies in brain, clocinnamox (0.32-25.6 mg/kg) dose-dependently decreased mu-opioid ([3H][D-Ala2,MePhe4,Gly-ol5]enkephalin; DAMGO) receptor Bmax with relatively minimal effects on Kd. Binding to delta-opioid receptor ([3H][D-Pen2,D-Pen5]enkephalin; DPDPE) and kappa-opioid receptor ([3H](5,7,8)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec -8-yl) benzeneacetamide; U69,593) was not affected by clocinnamox. The effect of clocinnamox was time-dependent in that the greatest changes in morphine potency and mu-opioid receptor density were observed within 24 h of administration and decreased with time (336 h). Although mu-opioid receptor density was decreased to less than 30% of control 24 h following clocinnamox (12.8 mg/kg) and had increased to 80% by 5 days, a solution hybridization assay for mu-opioid receptor mRNA transcript revealed no changes in the steady-state levels of this mRNA. These studies indicate that clocinnamox is an irreversible antagonist at the mu-opioid receptor since it appears to selectively affect receptor density with minimal effects on affinity. Furthermore, clocinnamox produces time- and dose-dependent changes in Bmax and these changes appear to be unrelated to changes in mu-opioid receptor mRNA. It is possible that the repopulation of brain by mu-opioid receptors following clocinnamox is mediated by an existing pool of receptors that are activated following treatment.

Animals↗

Quantitation of mu-opioid receptor (MOR-1) mRNA in selected regions of the rat CNS.

The mu opioid receptor (MOR-1) mRNA was quantified in rat CNS by a sensitive solution hybridization (SH) technique, employing a 32P-labeled riboprobe derived from the coding region of MOR-1 cDNA. In a Northern blot analysis this riboprobe hybridized to a 14 kb form of rat MOR-1 mRNA. The linear range of SH assay extends from 1 to 250 pg of MOR-1 sense transcript (equivalent to 9.3-2325 pg of MOR-1 mRNA). A microdissection technique for reproducible sampling of selected CNS regions, followed by the SH assay, allowed for a quantitative study of MOR-1 mRNA distribution. The highest levels of MOR-1 mRNA were present in medial thalamus (17.8 +/- 0.3 pg/micrograms RNA), and the lowest in the cerebellum (0.4 +/- 0.1 pg/microgram RNA). Hypothalamus, dorsal spinal horn, nucleus raphe, periaqueductal gray, and sensorimotor cortex contained intermediate levels. This distribution closely parallels the pattern of mu receptor binding, suggesting that both the mRNA and the receptor protein are colocalized within most of the regions studied.

Amino Acid Sequence↗

NMDA antagonists and clonidine block c-fos expression during morphine withdrawal.

The c-fos gene is expressed in the central nervous system (CNS) in response to neuronal stimuli. Induction of c-fos in certain CNS regions occurs following naltrexone precipitated withdrawal in morphine dependent rats. Non-competitive (MK801) and competitive (LY274614) NMDA receptor antagonists and clonidine, an alpha2 partial agonist, attenuate the intensity of naltrexone precipitated withdrawal. We determined the levels of c-fos mRNA by solution hybridization in several brain regions in control and morphine dependent rats following pretreatment with saline, MK801 (1 mg/kg, s.c.), LY274614 (100 mg/kg, i.p.), or clonidine (1.5 mg/kg, i.p.). Morphine treatment increased c-fos mRNA levels in striatum (STR) and amygdala (AMY). Naltrexone did not alter c-fos mRNA levels in placebo-treated rats. However, naltrexone increased c-fos mRNA levels in morphine dependent rats in the nucleus accumbens (NA), frontal cortex (FC), AMY, and hippocampus (HIP) but not in STR or spinal cord. Pretreatment with MK801 blocked this effect of naltrexone in AMY but not in NA, FC, or HIP, while pretreatment with LY274614 or clonidine blocked this effect of naltrexone in AMY and NA but not in FC or HIP. These results further delineate both the neuroanatomical pathways involved in morphine withdrawal and the locus of action of compounds that reduce morphine-withdrawal symptoms.

Animals↗

CNS levels of mu opioid receptor (MOR-1) mRNA during chronic treatment with morphine or naltrexone.

The CNS levels of mu opioid receptor (MOR-1) mRNA were determined by solution hybridization in rats treated chronically with morphine or naltrexone. Morphine treatment (2 x 75 mg pellets were implanted SC on Day 1 and 2 more on Day 4) resulted in the development of tolerance to morphine's antinociceptive (analgesic) effect, as assessed by the hot plate procedure on treatment Day 7. Following the hot plate test, selected CNS regions were obtained by microdissection. The levels of MOR-1 mRNA in pg/microgram RNA ranged from 0.7 in sensorimotor cortex to 15.3 in medial thalamus. MOR-1 mRNA levels were not altered in the dorsal horn of spinal cord, nucleus raphe magnus, periaqueductal grey, hypothalamus, medial thalamus, or sensorimotor cortex. In a separate experiment, a 2 day exposure to naltrexone (2 x 30 mg pellets) had no effect on CNS levels of MOR-1 mRNA; however, after an 8 day exposure a decrease was detected in the nucleus raphe magnus (by 28%), hypothalamus (by 21%), and medial thalamus (by 27%). Chronic exposure to morphine or naltrexone did not result in alterations in the size of full-length MOR-1 mRNA from rat brain, or in the size of the region protected by the MOR-1 riboprobe (i.e., the entire coding region). Thus, the neuroadaptive processes associated with the development of analgesic tolerance to morphine do not involve concurrent changes in the steady-state levels of MOR-1 mRNA. Chronic treatment with naltrexone appears to produce a region-specific downregulation of MOR-1 mRNA levels, which may be secondary to the naltrexone-induced increase in mu receptor binding.

Animals↗

Dextromethorphan shows efficacy in experimental pain (nociception) and opioid tolerance.

The oral antitussive dextromethorphan is a clinically available N-methyl-D-aspartate receptor antagonist. Dextromethorphan has analgesic efficacy in the experimental formalin test, blocks the nociceptive activation of the immediate-early gene, c-fos proto-oncogene, and prevents and reverses the development of opiate analgesic tolerance in experimental models. These data suggest that dextromethorphan should be evaluated in a controlled clinical trial for analgesic efficacy in zoster-associated neuralgia.

Dextromethorphan↗