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D Jaffe

Publications and source records attributed to D Jaffe.

At least 19 recordsLinked to original sources
PubMed1992

Synaptically activated increases in Ca2+ concentration in hippocampal CA1 pyramidal cells are primarily due to voltage-gated Ca2+ channels.

Changes in intracellular Ca2+ concentration ([Ca2+]i) in the soma and dendrites of hippocampal CA1 pyramidal neurons were measured using intracellularly injected fura-2. A large component of the [Ca2+]i elevation caused by high frequency stimulation of the Schaffer collaterals was correlated with the Na+ spikes triggered by the excitatory postsynaptic potentials (EPSPs). These spikes were generated in the soma and proximal dendrites and stimulated Ca2+ entry through voltage-gated Ca2+ channels. Suppressing spikes by hyperpolarizing the soma or by injecting QX-314 revealed a smaller nonspike component of Ca2+ entry. A substantial fraction of this component was mediated by the action of the EPSPs on voltage-gated Ca2+ channels, because it persisted in 2-amino-5-phosphonovaleric acid and because it was usually reduced when Ca2+ channel activity was suppressed by hyperpolarization. Ca2+ entry through the N-methyl-D-aspartate receptor channel could not be detected with certainty, perhaps because it was highly localized.

2-Amino-5-phosphonovalerate↗
PubMed1992

NMDA-receptor-independent long-term potentiation.

Although NMDA-R-dep LTP in the hippocampus has received much attention, it is clear that many types of LTP do not involve NMDA receptors. While early studies of NMDA-R-indep LTP were done in invertebrates, an NMDA-R-indep LTP is also seen in at least three excitatory pathways of the hippocampus. There would appear to be quite diverse mechanisms of induction of NMDA-R-indep LTP, although in most cases there is evidence, or at least a suggestion, that Ca2+ is involved. At the hippocampal CA3 MF synapse, activation of voltage-gated Ca2+ channels has been proposed as a trigger for LTP induction, and this may also be the case for certain types of LTP at the SC synapse in CA1 (25, 40). The modulation of both MF LTP and Ca2+ channels by beta-adrenoreceptor and muscarinic agonists suggests that specifically the L-type channel is critical for MF LTP induction. L-type Ca2+ channels may also be involved in NMDA-R-indep LTP at SC synapses (6, 40). Clearly more work is needed to test these possibilities. In addition, it will be interesting to discover whether voltage-gated Ca2+ channels play a role in LTP in other areas of the brain such as the cerebral cortex and amygdala (24).

Animals↗
PubMed1992

Efficacy of adding nebulized ipratropium bromide to nebulized albuterol therapy in acute bronchiolitis.

Nebulized ipratropium bromide is though to be synergistic with albuterol in therapy for acute childhood asthma. Because the efficacy of ipratropium in bronchiolitis is uncertain and some infants with bronchiolitis do not respond to nebulized albuterol alone, the following study was undertaken. In this double-blind, placebo-controlled trial, 69 infants between 6 weeks and 24 months of age who exhibited the first episode of acute bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg per dose) and ipratropium bromide (250 micrograms per dose) (group A, n = 36) or nebulized albuterol and normal saline (placebo) (group B, n = 33) for two doses, 1 hour apart. The two groups were comparable at baseline. Both therapies resulted in clinically significant improvement. However, the addition of ipratropium resulted in no additional benefit with respect to decrease in the respiratory rate (mean decreases 10.6/min vs decreases 8.6/min, P = .86), accessory muscle score (range 0 through 3) (decreases 0.92 vs decreases 0.82, z = -0.44), wheeze score (range 0 through 3) (decreases 0.94 vs 0.85, z = -0.20), oxygen saturation (increases 0.25% vs increases -0.33%, P = .86), or hospitalization rate (17 vs 10). The number of "nonresponders" and "clear responders" was also very similar in both groups. No toxicity was noted. The increase in heart rate was mild and similar in both groups (increases 6.7 vs increases 11.1). The power of the study to detect a difference between the two treatment groups in the respiratory rate change > or = 8/min is greater than 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Emergency management of blunt trauma in children.

Apart from the trend to nonoperative treatment of blunt abdominal injuries, based on accurate CT diagnosis, most of the recent and anticipated changes in pediatric trauma are organizational. They include resuscitation and triage before hospitalization, the use of designated trauma centers, resuscitation by trauma teams, noninvasive diagnosis and monitoring, comprehensive pediatric intensive care, the use of objective measures of outcome, and improved rehabilitation programs (Templeton JM: personal communication). The treatment of individual cases is based on simple but well-established principles. The key steps in management are to recognize children with life-threatening injuries (on the basis of the mechanism of injury or a Pediatric Trauma Score less than or equal to 8 or a Revised Trauma Score less than or equal to 11), to support the function of vital organs by establishing and maintaining adequate respiratory gas exchange and circulation, and to identify all important injuries by thorough and ongoing assessment.

Child↗
PubMed1991

Skateboarding injuries in children. A second wave.

Motivated by a number of skateboard-related injuries seen in an emergency department, we undertook an investigation of skateboarding injuries in the mid-1980s. We studied US Consumer Product Safety Commission injury frequency estimates, which indicated a resurgence of these injuries: 19,182 in 1984 and 37,180 in 1985. Children 10 to 14 years old were injured with greatest frequency. Nontrivial injuries were more common among children younger than 5 years old, reflecting a larger proportion of head and neck injuries. Boys sustained more frequent and more severe skateboard-related injuries. Observed injury patterns (head and neck injuries in younger children, extremity injuries in older children, and more severe head and neck injuries in older children) probably reflect the role of psychomotor development on both risk exposure and biomechanics. Likely prevention strategies include warnings against skateboard use by children younger than 5 years, prohibition of skateboards on streets and highways, and the promotion of use of helmets and other protective gear.

Adolescent↗
PubMed1991

Staphylococcal sepsis in HIV antibody seropositive psoriasis patients.

The cases of three HIV-positive men with generalized psoriasis and staphylococcal sepsis are reported. In each case the skin appeared to be the source of infection. While the patients received antibiotic therapy, the psoriatic plaques resolved despite minimal or no topical treatment.

Adult↗
PubMed1991

Fluorinated colchicinoids: antitubulin and cytotoxic properties.

The synthesis of B-ring and C-ring trifluoroacetamide-substituted colchicinoids and fluoro-substituted colchicineethylamides is presented. The B-ring trifluoroacetamido-substituted analogues exhibit moderate enhancement of potency compared to the nonfluorinated analogues for tubulin assembly inhibition and cytotoxicity toward two wild type cell lines. The C-ring substituted fluoroethylamides have reduced relative potencies in the same systems due to the strong electron-withdrawing effect of the fluoro derivatives. The fluoro colchicinoids are much more cytotoxic toward drug-resistant cell lines than to the wild type cell lines. Their enhanced potency is probably due to an effect of the fluoro moiety on functions specific to resistant cells and/or their higher hydrophobicity that may result in higher intracellular drug content. This finding may suggest the application of designed fluorinated anticancer drugs to overcome acquired resistance which may develop after several regiments of treatment with a nonfluorinated chemotherapeutic agent.

Animals↗
PubMed1991

Comparison of ras activation during epidermal carcinogenesis in vitro and in vivo.

Mouse epidermal cells have frequently been used to study the role of ras oncogenes in transformation in vivo and in vitro. After initiation with dimethylbenzanthracene (DMBA) in vivo, greater than 90% of the papillomas arising show the same A:T----T:A transversion at codon 61 of the H-ras gene, presumed to be the initiating event. On the other hand, initiation of epidermal cells in culture with carcinogens, followed by selection of initiated cells by resistance to calcium-induced differentiation, does not in general lead to the isolation of clones carrying mutant ras genes. Some other aspects of tumour progression in vivo can be reproduced using epidermal cells in culture: a rare DMBA transformant carrying the codon 61 mutation and expressing a 2:1 ratio of normal to mutant ras alleles gave rise upon transplantation to a more aggressive line in which the ratio of normal to mutant H-ras genes (and p21 products) was reversed. Similar alterations in ras gene dosage have been seen during progression of papillomas to carcinomas in vivo. We conclude that the mechanisms of initiation in vitro may differ substantially from in vivo, and depend on the particular culture conditions used. Moreover, the effects of mutant H-ras expression in mouse epidermal cells are variable depending on the genetic background of the cell.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Molecular events involved in ionizing radiation induced skin carcinogenesis.

The process of mouse skin tumor formation is subdivided into three operational stages. These stages include initiation, promotion and progression. Ionizing radiation has been found to be a weak initiating agent in the production of malignant squamous cell carcinomas, a complete carcinogen and an agent effective in causing tumor progression. Four skin tumor histologies have been seen with ionizing radiation: benign papillomas, squamous (SCC) and basal (BCC) cell carcinomas and fibrosarcomas. Distinct non-ras transforming genes have been detected in radiation initiated SCCs. A benign papilloma cell line (308) was used as a model system to study ionizing radiation induced progression. A variant 308 cell line (308 10 Gy 5) derived by irradiation of the parental 308 cell has been characterized. The 308 10 Gy 5 cells unlike the parental 308 cells form malignant tumors in athymic nude mice upon subcutaneous injection. The variant 308 10 Gy 5 cells unlike the parental cells also show by northern analysis high steady state levels of the following gene transcripts: stromelysin, metallothionein II A and the proto-oncogenes c-fos and c-jun. Transient transfection studies with a chimeric mouse stromelysin promoter sequence upstream of a chloramphenicol (CAT) reporter gene into 308 and 308 10 Gy 5 cells indicated that the stromelysin promoter was constitutively active in the 308 10 Gy 5 but not in the 308 cells. The ability to divide the process of carcinogenesis into multiple stages in the mouse skin mode has facilitated mechanistic studies that may elucidate the molecular pathways involved in radiation induced tumor development.

Animals↗
PubMed1991

Professional liability in a pediatric emergency department.

The risk of professional liability resulting from care given in the pediatric emergency department is a growing concern. This retrospective study examined the patients, diagnoses, and outcome of all threatened and actual claims that originated in the emergency department of a pediatric teaching hospital from 1977 through 1988. Twenty-five cases were identified by the hospital risk manager from approximately 320,000 visits (8.0 cases/100,000 visits); 22 charts were available for review. Ages of the patients ranged from 2 weeks to 13 years (mean 2.9 years, median 3.0 years). The patients' payment status was private insurance (n = 10), state public aid (n = 5), and no third-party payment source was listed for 7 children. Ten patients (46%) visited the emergency department between midnight and 8:00 AM, when an attending physician was not present. Return visits within 2 weeks for the same complaint occurred in 10 cases. The majority of the patients were discharged home (n = 18), and all of them had appropriate, adequately documented discharge instructions. The final diagnoses fell into four general categories: minor trauma/abuse (n = 7), neoplasms/chronic illnesses (n = 7), infectious diseases (n = 6), and appendicitis (n = 2). Review of the charts before knowledge of the legal outcome raised quality-of-care issues in 41% of the cases (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1990

Vomiting.

Explore the source record for details and available documents.

Child↗
PubMed1990

Induction of long-term potentiation at hippocampal mossy-fiber synapses follows a Hebbian rule.

1. The induction of long-term potentiation (LTP) at hippocampal mossy-fiber synapses requires an increase in postsynaptic [Ca2+]i but is independent of N-methyl-D-aspartate (NMDA) receptor activation. Voltage-gated Ca2+ channels have been proposed as one alternative source for raising [Ca2+]i during the induction of LTP. We tested the hypothesis that voltage-gated Ca2+ channel activation could mediate the induction of LTP by examining whether 1) the induction of mossy-fiber LTP was dependent on postsynaptic depolarization and 2) depolarization alone, of a magnitude presumably capable of activating Ca2+ channels, was sufficient to induce LTP. 2. Intracellular recordings were made from rat CA3 pyramidal cells in the hippocampal slice preparation under both current- and voltage-clamp conditions. Mossy-fiber postsynaptic potentials and currents were recorded before and after high-frequency stimulation (HFS) in the presence of 20-50 microM D-2-amino-5-phosphonovaleric acid (D-APV), an NMDA-receptor antagonist. 3. Voltage clamping of CA3 neurons between -80 and -100 mV during HFS reversibly blocked the induction of mossy-fiber LTP. Conversely, HFS paired with depolarizing-current steps under current clamp increased the magnitude of LTP compared with controls. These results indicate that mossy-fiber LTP is dependent on postsynaptic depolarization, and presynaptic activation alone was not sufficient to induce mossy-fiber LTP. 4. Depolarizing-current injections, which presumably depolarized CA3 cells to potentials sufficient to activate voltage-gated Ca2+ channels, had no effect on mossy-fiber synaptic responses. These results suggest that synaptic activation, in addition to postsynaptic depolarization, is required for the induction of mossy-fiber LTP. 5. Single mossy-fiber afferent volleys were also paired with depolarizing-current pulses. In the presence of APV, pairing of single-mossy-fiber excitatory postsynaptic potentials (EPSPs) with postsynaptic depolarization did not potentiate synaptic responses, suggesting that some form of HFS is also required for mossy-fiber LTP. In the absence of APV, however, the contamination of mossy-fiber synaptic responses by CA3-recurrent inputs resulted in some potentiation. 6. These results suggest that the induction of mossy-fiber LTP is dependent on both pre- and postsynaptic activity and thus follows a Hebbian rule for synaptic modification. In contrast to that demonstrated at Schaffer-collateral-commissural synapses, however, the induction of mossy-fiber LTP may require HFS in addition to postsynaptic depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Biological and molecular aspects of radiation carcinogenesis in mouse skin.

The process of mouse skin carcinogenesis can be operationally subdivided into at least three stages which have been termed initiation, promotion, and progression. Ionizing radiation has been found to be a weak initiator of malignant squamous cell carcinomas (SCCs) when radiation was followed by repeated treatments of the skin with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Besides SCCs, ionizing radiation was found to induce, independent of tumor promoters, basal cell carcinomas (BCCs), a tumor histology not normally seen with chemical carcinogens and mouse skin. Fractionated doses of 1 MeV electrons were found to enhance the conversion of chemically induced benign papillomas to malignant SCCs. In addition to the biological studies, questions related to dominant transforming genes and differential gene expression in the radiation-initiated mouse skin tumors have been explored. Distinct non-ras dominant transforming gene(s) have been detected in radiation-initiated, TPA-promoted SCCs. Differences in the expression pattern of tumor-associated genes were seen in comparing chemically to radiation-induced benign and malignant skin tumors. Therefore, ionizing radiation has been shown to be active in the initiation of malignant skin tumors and progression of benign to malignant tumors in the mouse skin. The ability to divide the process of carcinogenesis into multiple stages in the mouse skin model has facilitated mechanistic studies that may elucidate the molecular pathways involved in radiation-versus chemically induced tumor development.

Animals↗
PubMed1988

The clinical spectrum of renal disease associated with human immunodeficiency virus.

A nephrology consultation was called on 100 adult patients of 1,635 (6.1%) patients with human immunodeficiency virus (HIV) infection seen between 1982 and 1987 at the University of Miami/Jackson Memorial Medical Center. Renal disease was observed in all groups of patients with a risk factor for HIV infection with a lesser incidence, however, among homosexuals. Intravenous drug (IVD) use and possibly race appear to be important factors in the development of renal complications. Renal disease was the dominant clinical feature in eight asymptomatic HIV carriers and in 34 patients with AIDS-related complex (ARC) who had not developed the opportunistic infections and/or malignancies associated with acquired immunodeficiency syndrome (AIDS). Ninety-one percent of consultations were requested for evaluation of proteinuria and/or renal failure. Nephrotic range proteinuria, in excess of 3 g/24 h, was present in 52 patients, and was less prevalent in homosexuals than in other groups at risk. Renal failure (serum creatinine greater than or equal to 5 mg/dL), initially present in 32 patients, eventually developed in 69 and improved in only 18 of them. A renal biopsy, obtained for work-up of nephrotic syndrome (22 patients) or renal insufficiency (3 patients), uncovered a picture of focal and segmental glomerulosclerosis in all 25 instances. Overall, 76 patients are dead, seven are lost to follow-up, and 17 are alive, of whom eight (four HIV carriers, two patients with ARC, and two with AIDS) are on maintenance hemodialysis with a mean survival time of 217 days.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Outcome of patients with human immunodeficiency virus on maintenance hemodialysis.

Fifty-one adults with HIV infection, including 20 chronic hemodialysis patients with superimposed HIV infection and 31 patients with HIV-associated nephropathy requiring chronic maintenance hemodialysis were followed to evaluate survival on outpatient dialysis in relation to the clinical stage of the HIV infection. Regardless of when they contracted the infection, AIDS patients who required maintenance hemodialysis had a poor prognosis. All 17 patients who developed AIDS died after a mean of 93 +/- 32 days on hemodialysis (median 30 days; range 2 to 540 days). On the other hand, 12 asymptomatic HIV carriers were alive after a mean follow-up on chronic hemodialysis of 488 +/- 75 days (median 420 days; range 142 to 850 days); and five hemodialyzed patients with ARC were alive after 564 +/- 191 days (median 420 days; range 150 to 1230 days). The data confirm the lack of effectiveness of maintenance hemodialysis for prolonging life in patients with AIDS. This dismal prognosis was evident whether renal failure antedated HIV infection or whether it was HIV-associated. In asymptomatic HIV carriers and in patients with ARC, however, maintenance hemodialysis provides meaningful, long-term life support.

AIDS-Related Complex↗
PubMed1988

Pediatric emergency medicine fellowships: a survey.

A survey of 24 existing pediatric emergency medicine fellowship programs as of December 1987 was conducted in order to characterize the following attributes of training in pediatric emergency medicine: amount of clinical time, required and elective rotations, didactic and research experience, patient volume, and staffing. Time spent in the emergency department varies between three and 10 months annually, with a mean of 34.5 hours per week. Twenty-two (92%) of the programs have required rotations. All responding programs require research and some degree of didactic education. Patient volume varies between 20,000 and 70,000, with a median of 41,000. The data offered should act as a reference for the further development of new and existing programs.

Curriculum↗
PubMed1987

Single-dose captopril scintigraphy in the diagnosis of renovascular hypertension.

Renal scintigraphy with [99mTc]diethylenetriaminepentaacetic acid (DTPA) and/or sodium-iodine-131-o-iodohippurate (HIP) was performed before and after an oral dose of captopril (50 mg) in 18 patients with renovascular hypertension (RVH) due to renal artery stenosis (RAS) and 18 controls. In every patient with RVH, captopril induced, enhanced or sustained abnormal findings on HIP scintigraphy depending on the degree of RAS. With DTPA scintigraphy, renal function decreased after captopril in ten kidneys with RVH-related RAS and adequate baseline renal function, but this phenomenon was not evident in 11 kidneys with RVH and poor renal function. Captopril did not influence HIP or DTPA studies of kidneys with patent renal arteries (patients after successful renal angioplasty, patients with essential hypertension, contralateral kidneys of patients with unilateral RVH) or ipsilateral kidneys with mild and subcritical (less than 60%) RAS in patients without hypertension and/or normal renal vein renin activity. When HIP and DTPA scintigraphy were compared in the same patients, HIP demonstrated greater sensitivity and specificity than DTPA, particularly in patients with poor renal function. HIP scintigraphy before and after a single dose of captopril may provide a rapid sensitive and minimally invasive test for screening patients with hypertension.

Administration, Oral↗