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Biomedical subjects

E Kaufman

Publications and source records attributed to E Kaufman.

At least 19 recordsLinked to original sources
PubMed2005

Evidence for a multivalent interaction of symmetrical, N-linked, lidocaine dimers with voltage-gated Na+ channels.

The interaction of symmetrical lidocaine dimers with voltage-gated Na+ channels (VGSCs) was examined using a FLIPR membrane potential assay and voltage-clamp. The dimers, in which the tertiary amines of the lidocaine moieties are linked by an alkylene chain (two to six methylene units), inhibited VGSC activator-evoked depolarization of cells heterologously-expressing rat (r) Na(v)1.2a, human (h) Na(v)1.5, and rNa(v)1.8, with potencies 10- to 100-fold higher than lidocaine (compound 1). The rank order of potency (C4 (compound 4) > C3 (compound 3) > or = C2 (compound 2) = C5 (compound 5) = C6 (compound 6) >> compound 1) was similar at each VGSC. Compound 4 exhibited strong use-dependent inhibition of hNa(v)1.5 with pIC50 values < 4.5 and 6.0 for tonic and phasic block, respectively. Coincubation with local anesthetics but not tetrodotoxin attenuated compound 4-mediated inhibition of hNa(v)1.5. These data suggest that the compound 4 binding site(s) is identical, or allosterically coupled, to the local anesthetic receptor. The dissociation rate of the dimers from hNa(v)1.5 was dependent upon the linker length, with a rank order of compound 1 > compound 5 = compound 6 > compound 2 >> compound 3. The observation that both the potency and dissociation rate of the dimers was dependent upon linker length is consistent with a multivalent interaction at VGSCs. hNa(v)1.5 VGSCs did not recover from inhibition by compound 4. However, "chase" with free local anesthetic site inhibitors increased the rate of dissociation of compound 4. Together, these data support the hypothesis that compound 4 simultaneously occupies two binding sites on VGSCs, both of which can be bound by known local anesthetic site inhibitors.

Anesthetics, Local↗
PubMed2004

Comparison of the pharmacological properties of rat Na(V)1.8 with rat Na(V)1.2a and human Na(V)1.5 voltage-gated sodium channel subtypes using a membrane potential sensitive dye and FLIPR.

A novel, membrane potential sensitive dye and a fluorescence imaging plate reader (FLIPR) have been used to characterize the pharmacological properties of rat Na(v)1.8 voltage-gated sodium channels (VGSC) in parallel with rat Na(v)1.2a and human Na(v)1.5 VGSC subtypes, respectively. The sensitivity of recombinant Na(v)1.2a-CHO, Na(v)1.5-293-EBNA, and Na(v)1.8-F-11 cells to VGSC activators was subtype dependent. Veratridine evoked depolarization of Na(v)1.2a-CHO and Na(v)1.5-293-EBNA cells with pEC(50) values of 4.78 +/- 0.13 and 4.84 +/- 0.12, respectively (n = 3), but had negligible effect on Na(v)1.8-F-11 cells (pEC(50) < 4.5). Type I pyrethroids were without significant effect at all subtypes. In contrast, the type II pyrethroids deltamethrin and fenvalerate evoked direct depolarization of Na(v)1.8-F-11 and Na(v)1.5-293-EBNA cells. Deltamethrin potentiated the veratridine-evoked response in Na(v)1.8-F-11 cells by > or =20-fold, in contrast to a <or =3-fold potentiation of the response in Na(v)1.2a, and Na(v)1.5 cells. Tetrodotoxin (TTX) inhibited VGSC activator-evoked depolarization of Na(v)1.8-F-11 cells with a biphasic concentration-response curve. The calculated pIC(50) values were 8.05 +/- 0.25 (n = 4) and 4.32 +/- 0.21 (n = 4), corresponding to TTX inhibition of endogenous TTX-sensitive (TTX-S), and recombinant Na(v)1.8 TTX-resistant (TTX-R) VGSCs, respectively. With the exception of TTX, the potencies of a number of ion channel blockers for the Na(v)1.8, Na(v)1.2a, and Na(v)1.5 VGSC subtypes were similar. In summary, these high-throughput FLIPR assays represent a valuable tool for the determination of the relative potencies of compounds at different VGSC subtypes and may prove useful for the identification of novel subtype-selective inhibitors.

Animals↗
PubMed2004

[The use of conscious sedation versus general anesthesia in modern dentistry: rising ethical dilemmas].

Conscious sedation and general anesthesia have been in the use of the dental profession since the first half of the 19th century. Although seemingly appealing to use due to alleviation of pain and anxiety induced by the dental treatment, the alteration of consciousness level of dental patients is not without risk. Morbidity and mortality due to dental treatment performed under general anesthesia were investigated at the last decades of the 20th century. The mortality rates found in these investigations were surprisingly high comparing to researches of morbidity and mortality due to other medical procedures, performed under general anesthesia. Therefore, although general anesthesia is sometimes the only way to treat certain patients, maintaining strict indications for dental treatment under general anesthesia is necessary. Conscious sedation was found as a safer alternative for achieving a level of consciousness enabling dental treatment in those patients who are unable to receive treatment in normal dental clinic settings. We therefore believe that conscious sedation should be the golden standard for the treatment of those patients. The practicing of dentistry in patients who have need of dental treatment under special settings such as general anesthesia and sedation raises ethical dilemmas to the caregiver. The following review will summarize the available data on morbidity and mortality due to dental treatment given under general anesthesia and conscious sedation. The ethical questions arising from their practicing will be discussed and some answers shall be proposed.

Anesthesia, Dental↗
PubMed2003

Between scylla and charybdis: a bleomycin-exposed patient with Cohen syndrome.

Chemotherapy with bleomycin may cause a syndrome of pulmonary sensitivity to supranormal inspired oxygen concentrations that persists for an unknown period of time after exposure. We present a mentally retarded adolescent patient in whom supranormal inspired oxygen was temporarily necessary to manage her difficult airway. Subsequently her pulmonary function deteriorated acutely and, after intermittent stabilization, irreversibly. In this case, bleomycin exposure may have played a pivotal role in modulating minor insults to trigger fatal acute respiratory distress syndrome (ARDS).

Adolescent↗
PubMed2003

CO2 laser in oral graft-versus-host disease: a pilot study.

This paper is the first to report the benefits of CO2 laser treatment for pain control in severe oral chronic graft-versus-host disease (GVHD). A CO2 laser device was used during 17 treatment sessions in four patients. The CO2 laser was applied over the mucosal lesions using 1 W for 2-3 s/1 mm(2). This treatment resulted in a consistent and significant decrease in pain, measured using a standard visual analogue scale. These results suggest that the CO2 laser can be used for the alleviation of pain in oral chronic GVHD.

Adolescent↗
PubMed2002

Phase II trial of sequential high-dose chemotherapy with paclitaxel, melphalan and cyclophosphamide, thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer.

A single high-dose cycle of chemotherapy can produce response rates in excess of 50%. However, disease-free survival (DFS) is 15-20% at 5 years. The single most important predictor of prolonged DFS is achieving a complete response (CR). Increasing the proportion of patients who achieve a complete response may improve disease-free survival. Women with metastatic breast cancer and at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and G-CSF. The first intensification was paclitaxel (825 mg/m(2)), the second melphalan (180 mg/m(2)) and the third consisted of cyclophosphamide 6000 mg/m(2) (1500 mg/m(2)/day x 4), thiotepa 500 mg/m(2) (125 mg/m(2)/day x 4) and carboplatin 800 mg/m(2) (200 mg/m(2)/day x 4) (CTCb). Sixty-one women were enrolled and 60 completed all three cycles. Following the paclitaxel infusion most patients developed a reversible, predominantly sensory polyneuropathy. Of the 30 patients with measurable disease, 12 converted to CR, nine converted to a PR*, and five had a further PR, giving an overall response rate of 87%. The toxic death rate was 5%. No patient progressed on study. Thirty percent are progression-free with a median follow-up of 31 months (range 1-43 months) and overall survival is 61%. Three sequential high-dose cycles of chemotherapy are feasible and resulted in a high response rate. The challenge continues to be maintenance of response and provides the opportunity to evaluate strategies for eliminating minimal residual disease.

Adolescent↗
PubMed2002

[Emergencies evolving from local anesthesia].

Local anesthesia is without doubt the most frequently used drug in dentistry and in medicine. In spite of records of safety set by using these drugs, there is evidence to adverse reactions ranging from 2.5%-11%. Most of the reactions originate from the autonomic system. A recent, well-planned study indicates that adverse reactions are highly correlated to the medical status of the patient: the higher the medical risk, the greater the chance to experience an adverse reaction. This study also found that adverse reactions highly correlated to the concentration of adrenalin. Another recent study found a direct relationship between adverse reactions and the level of anxiety experienced by the patient and to the dental procedure. Most of the reactions in this study occurred either immediately at injection time and within 2 hours following the injection. Since the beginning of last century, vasoconstrictors have been added to local anesthesia solutions in order to reduce toxicity and prologue activity of the LA. However, today it is commonly agreed that this addition to local anesthesia should not be administered to cardiac patients especially those suffering from refractory dysrhythmias, angina pectoris, post myocardial infarction (6 months) and uncontrolled hypertension. Other contraindications to vasoconstrictors are endocrine disorders such as hyperthyroidism, hyperfunction of the medullary adrenal (pheochromocytoma) and uncontrolled diabetes mellitus. Cross reactivity of local anesthetic solutions can occur with MAO inhibitors, non specific beta adrenergic blockers, tricyclic antidepressants, phenothiazides and cocaine abusers. Noradrenaline added to local anesthetics as a vasoconstrictor has been described as a trigger to a great increase in blood pressure and therefore has been forbidden for use in many countries. This paper describes 4 cases of severe complications following the injections of local anesthesia of which three ended in fatality.

Anesthesia, Dental↗
PubMed2002

[Syncope in the dental environment].

Syncope or Fainting is, by far, the most common emergency situation in the dental practice. Syncope is defined as an abrupt, transient, short term loss of consciousness and postural tone, followed by spontaneous and complete recovery. The pathophysiology of syncope consists of a sudden cessation or decrease in cerebral perfusion. Differential diagnosis of these medical conditions is of paramount importance in uncovering unrecognized systemic diseases. The dental team plays an important role in the process of establishing the correct diagnosis by its ability to recognize and document all the clinical symptoms and signs evident at the time of fainting. The dental surgeon is expected to be familiar with the various etiologies of syncope and should be able to differentiate between them. This article provides the essentials of the diagnostic procedure and an approach to the evaluation of the unconscious patient.

Dental Care↗
PubMed2002

[Respiratory distress].

Dental treatment is usually conducted in the oral cavity and in very close proximity to the upper respiratory airway. The possibility of unintentionally compromising this airway is high in the dental environment. The accumulation of fluid (water or blood) near to the upper respiratory airway or the loosening of teeth fragmentations and fallen dental instruments can occur. Also, some of the drugs prescribed in the dental practice are central nervous system depressants and some are direct respiratory drive depressors. For this reason, awareness of the respiratory status of the dental patient is of paramount importance. This article focuses on several of the more common causes of respiratory distress, including airway obstruction, hyperventilation, asthma, bronchospasm, pulmonary edema, pulmonary embolism and cardiac insufficiency. The common denominator to all these conditions described here is that in most instances the patient is conscious. Therefore, on the one hand, valuable information can be retrieved from the patient making diagnosis easier than when the patient is unconscious. On the other hand, the conscious patient is under extreme apprehension and stress under such situations. Respiratory depression which occurs during conscious sedation or following narcotic analgesic medication will not be dealt with in this article. Advanced pain and anxiety control techniques such as conscious sedation and general anesthesia should be confined only to operators who undergo special extended training.

Central Nervous System Depressants↗
PubMed2002

[Chest pains in the dental environment].

Chest pain does not necessarily indicate cardiac disease. The most common causes of acute chest pain encountered in dental situations include hyperventilation, pulmonary embolism, angina pectoris and myocardial infarction. Stress and fear often cause rapid breathing or hyperventilation. This usually occurs in young adults and although the hyperventilating patient often complains of chest pain, this is rarely a manifestation of cardiac disease. Pulmonary embolism usually indicates the occlusion of a pulmonary artery causing severe chest pain. The primary clinical manifestation of angina pectoris is chest pain. Although most instances of anginal pain are easily terminated, the dentist must always consider the possibility that the supposed anginal attack is actually a sign of acute myocardial infarction (AMI). AMI is a clinical syndrome caused by a deficient coronary arterial blood supply to a region of myocardium that results in cellular death. There is a high incidence of mortality among AMI with death often occurring within 2 hours of the onset of signs and symptoms. The initial clinical manifestations of all types of chest pain can be similar. Therefore the dentist must develop proficiency in constituting a differential diagnosis and an efficient management protocol. As in most medical situations prevention is the most powerful tool. However, if chest pains do occur, measures such as airway management, oxygen supplementation, coronary artery dilation, analgesis and in extreme cases, cardiopulmonary resuscitation and evacuation to the emergency room, may be necessary.

Adult↗
PubMed2002

[Allergy-related emergencies].

Allergic reactions can develop to any of the drugs or materials commonly used in dentistry. They exhibit a broad range of clinical signs and symptoms ranging from mild, delayed reactions to immediate and life-threatening reactions developing within seconds. Allergies usually manifest themselves in reactions that are related to histamine release in one of three ways: skin reactions, respiratory problems and anaphylaxis. Anaphylaxis is the most critical allergic reaction in the dental environment. Measures such as airway management, oxygen supplementation, antihistamine, adrenaline and corticosteroid medication, cardiopulmonary resuscitation and evacuation to the emergency room, may be necessary.

Dental Materials↗
PubMed2002

[The potential dangers of endocrinal disorders].

The symptoms of most endocrine system diseases are usually clearly recognizable and most of the times are accompanied by a rich medical history. Many general practitioners are reluctant to treat such cases and prefer to refer these patients to specialists who are trained in management of the medically compromised thus increasing the chances of dental treatment without complications. However, sometimes endocrinal diseases develop slowly and their clinical manifestations are hidden or subclinical in nature. In these cases, neither the patient nor the dentist are aware of the condition and there is the potential of life threatening, emergency situations in what at first seem as simple, straightforward dental procedures. Therefore, the dentist must be able to recognize the clinical problem, differentiate between the different symptoms and initiate the proper management protocol. The most unstable endocrinal disorders that should be treated with great care are diabetes mellitus, mainly hypoglycemia, hyperthyroidism and adrenal insufficiency. The general practitioner dentist can treat patients suffering from these disorders providing the disease is well controlled and balanced and that the dental treatment is not very traumatic.

Adrenal Insufficiency↗
PubMed2002

[Legal and ethical considerations of emergencies in the dental office].

The dentist has the ethical and legal responsibility to anticipate emergency situations in correlation with the patient's medical status. He has the obligation to do all in his power to prevent emergencies from happening and to be prepared to manage any emergency that might occur. This article also discusses the importance of monitoring and documentation.

Dental Care for Chronically Ill↗
PubMed2001

The pharmacokinetics and pharmacodynamics of high-dose paclitaxel monotherapy (825 mg/m2 continuous infusion over 24 h) with hematopoietic support in women with metastatic breast cancer.

PURPOSE: We evaluated the pharmacokinetics and pharmacodynamics of high-dose paclitaxel (HDP) monotherapy (825 mg/m2 continuous infusion over 24 h) with peripheral blood progenitor cell (PBPC) and G-CSF support in 17 women with metastatic breast cancer. METHODS: Pharmacokinetic and pharmacodynamic data were collected in 17 women entered in a phase II trial of sequential HDP, and high-dose melphalan and cyclophosphamide/thiotepa/carboplatin. RESULTS: The maximal plasma concentration (Cmax), area under the plasma concentration time curve (AUC), apparent clearance (Clapp), duration of plasma concentration above 0.05 microM (t > 0.05 microM) for paclitaxel were (means SD): 9.11 +/- 7.45 microM, 145 +/- 88 microM x h, 8.06 +/- 2.90 l/h per m2 and 82.4 +/- 31.2 h, respectively. There was a significant correlation between the plasma paclitaxel concentration at 1 h (r2 = 0.87), 12 h (r2 = 0.85) and 23 h (r2 =0.92) and the AUC (P < 0.0001). Duration of neutropenia was brief (median 3 days, range 0-5 days) and neutrophil recovery occurred earlier (median 6 days, range 0-7 days) than could be attributed to infused PBPC. Median nadir count for platelets was 66 x 10(9)/l (range 13-160 x 10(9)/l). Pharmacodynamic analysis showed no correlation between pharmacokinetic parameters (Cmax, AUC, t > 0.05 microM) and time to neutropenic nadir, duration of neutropenia, platelet count nadir and grades of neuropathy or mucositis. In ten patients in whom detailed neurologic and nerve conduction studies were performed, linear regression analysis showed a significant correlation between pre- and post-HDP treatment total neuropathy scores (r2 = 0.46, P = 0.03). CONCLUSIONS: HDP (825 mg/m2 continuous infusion over 24 h) did not appear to be myeloablative. The degree of neurotoxicity subsequent to HDP was associated with the degree of baseline neuropathy but was not predictable from pharmacokinetic parameters.

Adult↗
PubMed2001

Continuous radiographic visualization of the mandibular nutrient canals.

The continuous radiographic appearance of the course of mandibular nutrient canals (NC), originating from the incisive branch of the inferior alveolar neurovascular bundle bilaterally, showing anastomoses and terminating in the interdental area of the anterior teeth, is reported for the first time.

Female↗
PubMed2001

Reduction of paclitaxel-induced peripheral neuropathy with glutamine.

PURPOSE: Dose-limiting toxicity of many newer chemotherapeutic agents is peripheral neuropathy. Prior attempts to reduce this side effect have been unsuccessful. We report on the possible successful reduction of peripheral neuropathy with glutamine administration after high-dose paclitaxel. EXPERIMENTAL DESIGN: Patients entered a high-dose chemotherapy protocol in which the first high-dose cycle was paclitaxel at 825 mg/m(2) given over 24 h. The first cohort of patients did not receive glutamine, and the second cohort of patients received glutamine at 10 g orally three times a day for 4 days starting 24 h after completion of paclitaxel. Neurological assessment was performed at baseline, and at least 2 weeks after paclitaxel, and consisted of a complete neurological exam and nerve conduction studies. RESULTS: There were paired pre- and post-paclitaxel evaluations on 33 patients who did not receive glutamine and 12 patients who did. The median interval between pre- and post-exams was 32 days. For patients who received glutamine, there was a statistically significant reduction in the severity of peripheral neuropathy as measured by development of moderate to severe dysesthesias and numbness in the fingers and toes (P < 0.05). The degree and incidence of motor weakness was reduced (56 versus 25%; P = 0.04) as well as deterioration in gait (85 versus 45%; P = 0.016) and interference with activities of daily living (85 versus 27%; P = 0.001). Moderate to severe paresthesias in the fingers and toes were also reduced (55 versus 42% and 64 versus 50%, respectively), although this value was not statistically significant. All of these toxicities were reversible over time. CONCLUSIONS: Glutamine may reduce the severity of peripheral neuropathy associated with high-dose paclitaxel; however, results from randomized, placebo-controlled clinical trials will be needed to fully assess its impact, if any. Trials are currently ongoing to assess its efficacy for standard-dose paclitaxel in breast cancer and other tumors for which peripheral neuropathy is the dose-limiting toxicity.

Activities of Daily Living↗
PubMed2000

Analysis of saliva for periodontal diagnosis--a review.

BACKGROUND: This review examines salivary constituents as potential diagnostic tests for periodontal disease. Saliva is a fluid that is readily available and contains locally-produced microbial and host response mediators, as well as systemic (serum) markers that may prove to be an aid in the diagnosis of periodontal disease. METHODS: A medline search was conducted and the relevant literature concerning the applications of saliva for periodontal diagnosis was reviewed. RESULTS: Based on the literature, salivary markers that have been studied as potential diagnostic tests for periodontal disease include proteins of host origin (i.e., enzymes, immunoglobulins), phenotypic markers, host cells, hormones (cortisol), bacteria and bacterial products, ions and volatile compounds. CONCLUSIONS: A number of markers show promise as sensitive measures of disease and the effectiveness of therapy. At this time, host-derived enzymes and other inflammatory mediators orginating from the gingival crevice appear to hold the greatest promise as salivary diagnostic tests for periodontal disease. Longer-term longitudinal studies, however, are required to establish the relationship between specific markers and progression of periodontal disease. Furthermore, analysis of saliva may offer a cost-effective approach to assessment of periodontal disease in large populations.

Bacteria↗