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Biomedical subjects

S Elad

Publications and source records attributed to S Elad.

At least 19 recordsLinked to original sources

Fludarabine-based reduced intensity conditioning for stem cell transplantation of Fanconi anemia patients from fully matched related and unrelated donors.

Reduced intensity conditioning has been suggested as a desirable therapeutic modality for the treatment of patients with malignant and nonmalignant indications, but it seems particularly attractive for patients with Fanconi anemia due to their increased sensitivity to chemoradiotherapy. Between November 1996 and September 2003, 7 patients (1 male and 6 female; age range, 3-31 years; median age, 9.5) were conditioned with a fludarabine-based protocol for stem cell transplantation without radiation. In vivo T-cell depletion was accomplished with anti-thymocytic globulin or Campath-1H (alemtuzumab). Graft-versus-host disease prophylaxis consisted of low-dose cyclosporine alone. Eight transplantations were carried out for 7 patients using bone marrow, peripheral blood, and/or cord blood as sources of stem cells. All patients received transplants from HLA-A, -B, -C, and -DR matched donors, 5 from family members and 2 from matched unrelated donors. One patient did not engraft her first matched unrelated donor and underwent a second transplantation from another matched unrelated donor, after which she engrafted well. All 7 patients are alive and well, fully reconstituted with donor cells, and with 100% performance status. In conclusion, fludarabine-based preparative protocols are well tolerated, facilitate rapid engraftment with minimal toxicity, and should be considered an essential component of choice for patients with Fanconi anemia.

Adult↗

A prospective, double-blind phase II study evaluating the safety and efficacy of a topical histamine gel for the prophylaxis of oral mucositis in patients post hematopoietic stem cell transplantation.

The aim of this study was to evaluate the safety, tolerability and efficacy of a topical gel containing histamine dihydrochloride (HDC) versus a placebo gel in preventing oral mucositis in hematopoietic stem cell transplantation (HSCT) patients. A total of 45 patients post-HSCT were enrolled in a prospective longitudinal, placebo-controlled, double-blind study. Patients were evaluated twice weekly for oral mucositis (OMAS, NCI score), oral pain (VAS), oral function and salivary flow rate. Compliance was assessed using a patient diary. Oral mucositis developed in 85% of the HDC group and 63% of the placebo group. The mean maximal intensity for NCI score was 1.45+/-1 in the HDC group and 1.21+/-1.27 in the placebo group (P=0.37). The mean duration of oral mucositis was 4.7+/-3.6 and 2.33+/-2.23 days in the HDC and placebo groups, respectively (P=0.06). The same trends were measured with OMAS. Visual analogue scale for oral pain and oral function was not significantly different between the two groups. Histamine dihydrochloride was found to be safe. In the search for topical agents for the prevention of mucositis, we found that HDC neither improves nor worsens oral mucositis in HSCT patients. The balance between the pro- and anti-inflammatory effects of HDC should be investigated further in order to acquire a clinically effective topical medication based on its anti-inflammatory properties.

Aged↗

Osteomylelitis and necrosis of the jaw in patients treated with bisphosphonates: a comparative study focused on multiple myeloma.

It was reported that multiple myeloma (MM)-patients suffer from a higher incidence of osteomyelitis and necrosis of the jaws than patients treated with bisphosphonates for other reasons. The aim of this study is to report about 57 cases of bisphosphonate-related osteomyelitis and necrosis of the jaws (BON) and to investigate the differences between BON in MM and non-MM patients. Clinical and laboratory data of 57 cases were assessed. The features of BON and clinical-outcome were compared between the two groups. Treatment approach was assessed as a contributing-factor to treatment-outcome. Clinical presentation included exposed bone, pain, swelling and suppuration with little variation between the two groups. Past dento-alveolar surgery was common in both study-groups. Treatment outcome was poor (33% and 25% responded to treatment in MM group and non-MM group, respectively). Treatment modality did not affect the treatment outcome. The clinical presentation described in this case series should alert the physician to the possibility of BON. Although the literature shows a higher incidence of BON in MM patients compared to non-MM patients, our study suggests that the severity of the clinical presentation and the response to treatment are not worse in MM patients compared with non-MM patients. The predisposition of MM patients to BON should be further investigated.

Aged↗

Low transplant-related mortality with allogeneic stem cell transplantation in elderly patients.

Historically, age >60 years was considered a contraindication for allogeneic stem cell transplantation (allo-SCT). In recent years, elderly (>60 years) patients have become eligible for allo-SCT due to the application of reduced intensity conditioning (RIC). The present report summarizes our cumulative experience in a cohort of 17 elderly patients (age 60-67, median 62.5 years) with hematological malignancies treated with 18 allo-SCT procedures, mostly nonmyeloablative. In all, 14 patients received fludarabine and busulfan/busulfex regimen, three patients were conditioned with the fludarabine and low-dose TBI and one patient received busulfan alone. All patients displayed tri-lineage engraftment. The time to recovery of absolute neutrophil count >/=0.5 x 10(9)/l was 9-27 days (median 14 days). The time interval to platelet recovery >/=20 x 10(9)/l was 3-96 days (median 11 days). Veno-occlusive disease occurred only in 3/18 procedures and subsided with conventional treatment. Nonfatal transplant-related complications occurred in 6/18 (33.3%) procedures including: renal failure, arrhythmia, CNS bleeding, cystitis, typhlitis and gastrointestinal bleeding. Transplant-related mortality occurred in 6/18 (33.3%) episodes. Of the 17 patients, 12 (12/18 episodes) were discharged. Five of 17 (29%) patients survived (median follow-up 11 m, range 8-53 m). Our data suggest that RIC-allo-SCT may be safely applied in the elderly, suggesting that allogeneic immunotherapy may become an important tool for treatment of hematological malignancies without an age limit.

Aged↗

Rhinolalia as a presenting sign of pneumomediastinum complicating post peripheral blood stem cell transplantation bronchiolitis obliterans.

A 26-year-old male with graft vs. host disease (GVHD) presented with rhinolalia (a squeaky voice of nasal quality) as a presenting sign for pneumonasopharynx and pneumomediastinum secondary to bronchiolitis obliterans. The patient underwent HLA-identical related peripheral blood stem cells transplantation 8 months before the diagnosis. Three weeks after transplantation he began to suffer from GVHD Grade III that involved the gut, liver, and skin and later on the lungs. Due to severe obstructive bronchiolitis obliterans the patient developed intensive cough evolving into pneumomediastinum and pneumonasopharynx with rhinolalia. The patient was treated conservatively with complete resolution. Although rare, pneumomediastinum and pneumonasopharynx can be a life-threatening event, and one should be aware of the signs and symptoms on physical examination, which may be as subtle as rhinolalia alone.

Adult↗

A new minimally ablative stem cell transplantation procedure in high-risk patients not eligible for nonmyeloablative allogeneic bone marrow transplantation.

Nonmyeloblative stem cell transplantation (NST, SCT) aims to induce host-versus-graft tolerance for subsequent immunotherapy of underlying disease with alloreactive donor lymphocytes, focusing on well-tolerated conditioning suitable for elderly individuals or for other risk factors. However, there is a subset of high-risk patients who cannot tolerate NST. A new protocol consisting of fludarabine 30 mg/m(2) x 6 days (days -8 to -2), very-low-dose busulfan (2 mg/kg x 2 days, days -6 to -5), without anti thymocyte globulin (ATG), was employed in 11 high-risk patients aged 26-58 years. Graft-versus-host-disease (GVHD) prophylaxis consisted of low-dose and short-course cyclosporine-A (CSA) alone. One patient died during the nadir due to pulmonary complications. Other patients showed rapid three-lineage engraftment, without complete aplasia; 6/10 patients did not require platelet transfusion and 8/10 had full donor chimerism without transient mixed chimerism. Owing to intentional selection of highly poor-risk patients, overall mortality was high and only one patient survived. Acute GVHD (>/=grade I) occurred in 8/10 evaluable patients, 5/8 while off CSA; 5/8 developed grade III-IV acute GVHD. It appears that our modified, minimally ablative stem cell transplantation (MST) may be used for high-risk patients in need of allo-SCT. Furthermore, although the MST conditioning is not myeloablative, it results in myeloablation of the host hematopoietic system, mediated by alloreactive lymphocytes.

Adult↗

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↗

[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↗

[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↗

[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↗

[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↗

[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↗

[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↗

[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↗

Ultraviolet B irradiation: a new therapeutic concept for the management of oral manifestations of graft-versus-host disease.

Ultraviolet irradiation inhibits the proliferative responses of lymphoid cells to mitogens and alloantigens by inactivation of T lymphocytes and antigen-presenting cells. Its immunosuppressive capacity led to the introduction of UV irradiation into clinical practice for the treatment of dermatologic manifestations of chronic graft-versus-host disease. The cumulative experience with psoralen-UV-A rays in the treatment of cutaneous and oral graft-versus-host disease was the incentive for the application of oral UV-B rays in 2 patients with oral graft-versus-host disease signs and symptoms after allogeneic marrow transplantation. Intraoral UV-B irradiation (0.02 mJ/cm(2)) was administered 2 or 3 times per week on an ambulatory basis; the dose was increased by 0. 02 mJ/cm(2) every fourth session. Both patients responded early and satisfactorily, displaying only minimal side effects at a relatively low cumulative dose. Intraoral UV-B proved a valuable modality in the treatment of resistant chronic oral graft-versus-host disease.

Adult↗

Systemic absorption of lidocaine after topical application for the treatment of oral mucositis in bone marrow transplantation patients.

This paper evaluates lidocaine absorption via oral mucosa following its topical application for symptomatic treatment of bone marrow transplantation (BMT)-induced oral mucositis. Five patients with high-grade oral mucositis after allogeneic BMT were entered consecutively into the study. Five healthy individuals served as controls. All 10 participants rinsed their mouth with 5 ml of a 2% lidocaine solution for 1 min, after which they expectorated the liquid. Blood samples were drawn at 1, 5, 10, 20, 30 and 60 min after rinsing and centrifuged. Plasma lidocaine levels were measured by fluorescence polarization immunoassay. In the BMT patients, plasma lidocaine levels were lower than the therapeutic range of this drug (0.2 microg/ml vs 1.5-5.5 microg/ml), while in the controls no detectable lidocaine levels were noted. The data from this preliminary study indicate that lidocaine prescribed as an anesthetic mouthwash in BMT patients with oral mucositis results in minor systemic absorption of the drug.

Administration, Topical↗

Chronic graft-versus-host disease treated with UVB phototherapy.

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation. Immunosuppressive treatment regimens carry the potential of causing severe morbidity and mortality, so that additional modes of therapy with fewer side-effects are clearly needed. Five cGVHD patients (sclerodermoid cGVHD in two patients, lichenoid cGVHD in one patient and intraoral cGVHD in two patients), who had not responded to standard immunosuppressive drugs, were treated with adjuvant UVB phototherapy. The patient with lichenoid cGVHD experienced complete clearing of cutaneous lesions, whereas both patients with sclerodermoid cGVHD experienced significant relief of pruritus, but showed no change of the sclerodermoid skin lesions. Intraoral lesions cleared in one patient. The effects of UVB phototherapy were furthermore documented by measurement of skin viscoelasticity and mouth opening. No side-effects were encountered. This preliminary study suggests that UVB phototherapy is useful as an adjuvant therapeutic modality in intraoral and cutaneous lichenoid cGVHD.

Adolescent↗

Thalidomide-induced perioral neuropathy.

Thalidomide was administered as a therapeutic agent for chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation in a patient with breast cancer. Although side effects of thalidomide have been described earlier, this is the first instance of perioral neuropathy associated with thalidomide treatment. Awareness of this specific side effect may contribute to early diagnosis and appropriate treatment.

Antineoplastic Combined Chemotherapy Protocols↗