Search PubMed⌕ Search

Biomedical subjects

M Mittelman

Publications and source records attributed to M Mittelman.

At least 37 records · Page 2Linked to original sources
PubMed1997

Recombinant human erythropoietin in the treatment of multiple myeloma-associated anemia.

UNLABELLED: Multiple myeloma (MM) is commonly associated with anemia. Several causes have been implicated but inadequate erythropoietin (Epo) production appears to be important. This single-institute open-label, non-comparative clinical trial was undertaken in order to evaluate serum Epo levels in patients with MM and to study the efficacy and toxicity of recombinant human Epo (rHuEpo) in the treatment of MM-associated anemia. MM patients with a baseline hemoglobin (Hb) level of < 11 g/dl received rHuEpo 150 U/kg 3 times/week subcutaneously, with a possible dose increase to 300 U/kg if no response was observed after 4 weeks. The study was designed for 12 weeks, although some responders continued rHuEpo. The study endpoints were determined by an increase in Hb and a decrease in blood transfusion requirements (BTR). Seventeen patients were enrolled in the study. The median serum Epo level was 150 mU/ml (range 11-232). Four patients did not complete the study for reasons unrelated to rHuEpo, but to their underlying MM. Twelve patients (70.6%) responded with an increase in their Hb levels. One patient (5.9%) responded partially. The median Hb level rose from 9.4 g/dl (range 7.3-10.7) at study commencement to 12.5 g/dl (range 9.0-15.2). Six of the 11 patients who were transfusion dependent enjoyed a complete abolition of BTR. The response was also interpreted as an improved quality of life: 3 patients reported a decrease of 1 level in their WHO performance status (PS) score; in 8 patients, the PS declined by 2 grades and 1 patient enjoyed PS reduction by 4 scores. Six patients continue to receive rHuEpo up to 18 months, with a good response and a smaller maintenance dose. Four patients reported flu-like symptoms, 2 suffered from a local irritation and 1 experienced a transient controlled elevation of blood pressure. SUMMARY: (1) Pretreatment endogenous serum Epo levels were relatively low in all patients studied with MM-associated anemia; (2) rHuEpo was well tolerated in these patients; (3) rHuEpo was highly effective in the treatment of anemia in MM, and (4) the response to rHuEpo is characterized by an increase in Hb levels, a reduction in BTR and an improvement in the WHO PS score.

Adult↗
PubMed1997

Ultrastructural observations on bone marrow cells of 26 patients with myelodysplastic syndromes.

Bone marrow aspirates from 26 patients with myelodysplastic syndrome (MDS) were examined using transmission electron microscopy. The red blood cell precursors in 9 patients showed varying degrees of dyserythropoiesis including the presence of 2 or more nuclei, nuclei with bizarre shape and iron deposits in the mitochondria. The myeloid series showed a tendency to hypogranulation (5 patients) and in 2 patients there were signs of platelet phagocytosis. The monocytes had a normal ultrastructure except for one patient with chronic myelomonocytic leukemia (CMML) with transformation to acute myelo-monocytic leukemia (AMML). In this case, the monocytes were immature, with markedly convoluted nuclei and scanty heterochromatin. The lymphocytes also had a normal appearance, except for one patient in whom the lymphocytes were immature, with lobulated nuclei and suggested transformation of MDS to acute lymphoblastic leukemia. The plasma cells in 3 patients were slightly increased in number and in one of them Russell bodies were seen both in the cytoplasm and the nucleus. The megakaryocytic series showed a shift to the left and in one patient there were signs of emperipolesis. The alterations in the hematopoietic cells in patients with MDS described in the present study indicate that the electron microscope may supplement light microscopic findings and help in the establishment of a correct diagnosis. This may be also evident in those cases of MDS in which the very early stages of leukemic transformation cannot be easily detected by light microscopy.

Adolescent↗
PubMed1997

Non-Hodgkin's lymphoma presenting with coagulopathy due to anti-phospholipid antibody syndrome.

The clinical presentation of non-Hodgkin's lymphoma (NHL) has been well recognized and characterized. Among the unusual presentations immunological and autoimmune phenomena have been reported. We describe a patient in whom NHL presented with lupus anticoagulants. The immunological and coagulation abnormalities at presentation and the complication during the course of NHL as well as their prognostic implication are discussed.

Aged↗
PubMed1997

[Therapeutic and toxic theophylline levels in asthma attacks--is there a need for additional theophylline?].

Although first-line therapy for bronchial asthma has changed over the past decade to anti-inflammatory medication such as inhaled corticosteroids and cromolyn with possible addition of beta-agonists, theophylline is still useful and therefore widely used. However, several studies have raised serious questions regarding its efficacy in acute asthmatic exacerbations. These studies, the narrow therapeutic range of the drug, the frequency of side effects and interactions with common drugs, and individual variation in clearance and metabolism, have prompted its reevaluation in the management of asthma. Therapeutic serum levels of theophylline are between 10 to 20 mcg/ml. Most adults achieve these concentrations with daily slow-release oral theophylline preparations, 200-400 mg (approximately 10 mg/Kg) twice a day. However, when such a patient presents to the emergency room (ER) in an asthmatic attack, immediate intravenous theophylline is often given, regardless of maintenance treatment. Since the rationale for this common therapeutic approach has been challenged, the current study was undertaken. Serum theophylline levels were measured in 23 consecutive asthmatics presenting to the ER in an acute attack. 15 (68%) had therapeutic levels (above 10 mcg/ml) and 2 had toxic levels (above 20 mcg/ml), prior to receiving the standard intravenous theophylline dose given for an attack. These data indicate that most patients with bronchial asthma on oral maintenance theophylline do not require additional intravenous theophylline when in an attack. It probably will not benefit them and may even induce serious theophylline toxicity.

Adult↗
PubMed1997

Splenectomy for haematological diseases--a single institution experience.

OBJECTIVES: To evaluate our experience with splenectomy for haematological disease over 15 years, focusing on the diseases and indications requiring surgery, the complications and the haematological results. DESIGN: A single institution retrospective analysis. SETTING: Departments of Surgery, Internal Medicine and Haematology, Rabin Medical Center, Hasharon Hospital, Petah-Tikva, Israel. PATIENTS: Sixty-nine patients undergoing splenectomy for haematological diseases between 1980 and 1994. PARAMETERS STUDIED: (1) the patient characteristics; (2) the haematological disorders and the indications for splenectomy; (3) the splenic size; (4) perioperative complications; (5) the haematological and other results of surgery. RESULTS: The common disease requiring splenectomy in our patient population was immune thrombocytopenic purpura (ITP). Eighteen patients (26%) suffered from ITP, 12 (17.4%) had lymphoproliferative (LP) disorders, including 11 patients with non-Hodgkin's lymphoma (NHL), 9 (13%) immune haemolytic anaemia (IHA), 8 (11.6%) Hodgkin's disease (HD), and 8 patients with myeloproliferative diseases (MPD). Fifty-two patients (75.4%) underwent surgery for therapeutic purposes while 25 patients (36.2%) underwent diagnostic surgery. Eight patients were operated on for both indications. Patients with HD and ITP were younger (mean age in the 30th year) as opposed to patients with congestive splenomegaly and LP (mean age in the 60th year). Most patients with ITP, NHL and IHA were female. Patients with HD and ITP had a small spleen (< 300 g), in contrast with HCL and MPD (> 2400 g). No perioperative mortality was observed. Twenty-one patients (30.4%) experienced perioperative complications, including bleeding in 9 patients (13%) and infection in 10 patients (14.5%). Of the 34 patients evaluable for platelet response to splenectomy, 26 (76.5%) achieved complete response (CR), including 15 of 18 patients with ITP. Eleven of the 17 (64.7%) anaemic patients evaluable for haemoglobin (Hb) response achieved CR. Eight of the 9 leucopenic patients obtained CR. In 15 patients, splenectomy established the diagnosis, including 8 patients with NHL. In 2 others, surgery confirmed the tentative diagnosis. In 2 of the 8 HD patients the spleen was found to be involved. CONCLUSIONS: From both therapeutic and diagnostic standpoints splenectomy is a relatively safe and effective procedure. However, no long-term follow-up data are provided to allow conclusions regarding the long-term prognosis of diseases such as myelo- or lymphoproliferative disorders.

Adolescent↗
PubMed1996

[Bleeding due to platelet dysfunction as a presenting symptom of systemic lupus erythematosus].

A 32-year-old woman was admitted for evaluation of fever, blurred vision in the left eye, nasal and gingival bleeding and arthralgia. There was a macular hemorrhage, a tender mass in the left lower abdomen and edema of both legs. She also had anemia, mild thrombocytopenia, platelet function abnormalities, kidney dysfunction, and albuminuria. Serology was positive for antinuclear antibodies and double-stranded DNA; complement level was low, and circulating anticoagulants were present. Kidney biopsy established the diagnosis of systemic lupus erythematosus (SLE). Abdominal sonography demonstrated perisplenic and pelvic bleeding. A pulse therapy of corticosteroids with low-dose oral cyclophosphamide, along with platelet transfusions and infusions of deamino-d-arginine vasopressin resulted in symptomatic and laboratory improvement. Bleeding stopped, platelet function became normal, kidney function tests returned to normal and she became seronegative. It is emphasized that platelet function abnormalities are rare in SLE. The thrombocytopenia was too mild to cause spontaneous bleeding, and lupus anticoagulant is usually associated with thromboembolic complications and not with spontaneous bleeding. It is therefore conceivable that in this case platelet function abnormalities were responsible for the spontaneous bleeding, the presenting sign which led to establishing the diagnosis.

Adult↗
PubMed1996

Analysis of the erythropoietin receptor gene in patients with myeloproliferative and myelodysplastic syndromes.

The human erythropoietin receptor (EpoR) gene has been cloned and characterized. Very few EpoR genetic abnormalities have been reported so far. Polycythemia vera (PV) is characterized by low/normal serum erythropoietin (Epo) levels with proposed Epo hypersensitivity. Myelodysplastic syndromes (MDS) are characterized by refractory anemia with variable serum Epo levels. Several reports have suggested EpoR abnormalities in both types of stem cell disorders. We analyzed DNA obtained from peripheral blood mononuclear cells of seven healthy controls, 20 patients with myeloproliferative disorders (MPD, 11 patients with PV, five agnogenic myeloid metaplasia with myelofibrosis, four essential thrombocytosis) and eight patients with refractory anemia with ringed sideroblasts (RARS), an MDS variant. The DNA was digested with four restriction enzymes (BamHI, Bgl II, Sacl and HindIII), followed by Southern blot, using a 32P radiolabeled probe, containing 1.5 kb of the human EpoR cDNA. All 20 MPD patients and seven out of the eight MDS patients demonstrated a restriction pattern which was identical to the seven normal controls, as well as to the erythroid cell line K562, and also consistent with the expected restriction map, for all four enzymes tested. One RARS patient had a normal pattern with three enzymes but a different one with HindIII. The HindIII 12 kb large band was replaced by a faint 12 kb band and a new (about 9 kb) band appeared. The EpoR restriction map and the normal pattern obtained with the other three enzymes suggest that this patient has a 3 kb upstream deletion in one allelic EpoR gene. The same molecular pattern was detected in the patient's sister, who suffers from anemia with mild bone marrow (BM) dyserythropoiesis and plasmacytosis. Northern blot analysis showed that the patient's BM RNA carried normal EpoR message. This familial pattern may represent polymorphism. However, the patient's very high serum Epo level, her resistance to treatment with recombinant Epo, and the abnormally low growth rate of in vitro erythroid cultures, suggesting poor response to Epo in this MDS patient as well as the hematological abnormalities in her sister, support the speculation that the different EpoR gene might serve as a genetic predisposing marker and potentially could be involved (probably via post-transcriptional mechanisms and by an interaction with other factors or cytokines) in the pathogenesis. Our data suggest that the EpoR is intact in MPD and in most patients with RARS. One RARS patient had a familial different genetic structure, which could represent polymorphism. However, we can speculate also that it might be involved in the pathogenesis of the disease.

Aged↗
PubMed1996

Ocular manifestation of hairy cell leukemia with dramatic response to 2-chloro-deoxy-adenosine.

PURPOSE: To demonstrate that hairy cell leukemia may involve the eye. METHODS: We examined a patient who had a unique ocular manifestation of hairy cell leukemia with severe panuveitis in one eye and leukemic retinopathy in the fellow eye. RESULTS: Therapy with 2-chloro-deoxy-adenosine, a drug recently introduced for treatment of hairy cell leukemia, led to dramatic improvement of the ocular complications. CONCLUSIONS: Hairy cell leukemia may involve the eye and ocular symptoms may respond to systemic treatment with 2-chloro-deoxy-adenosine.

Aged↗
PubMed1996

Life-sustaining treatment decisions by spouses of patients with Alzheimer's disease.

OBJECTIVE: To examine the anticipated decisions to consent to or to forgo life-sustaining treatment by spouses of patients with Alzheimer's disease and to describe the relationship of spouse and patient characteristics to predicted decisions. DESIGN: Prospective quantitative study. SETTING: The Aging and Dementia Research Center (ADRC), part of an Alzheimer's Disease Center Core Grant, at New York University Medical Center. PARTICIPANTS: Fifty spouse caregivers of Alzheimer's disease patients, evaluated at the ADRC, who had a minimum Stage 4 on the Global Deterioration Scale. MEASUREMENTS: Spouses were presented with two conditions (critical illness and irreversible coma) and rated their agreement with, certainty of, and comfort with four treatments (resuscitation, breathing machine, feeding tube, and antibiotics). Data were also obtained as to patients' current quality of life, spouses' standard of decision-making, and spouse burden. RESULTS: Eighteen of 50 patients had a durable power of attorney for health care, 20 of 50 had a living will, and 26 of 50 had neither. In the face of critical illness, almost equal numbers of spouses would consent to or forgo CPR, 28 of 50 would forgo a breathing machine, 21 of 50 a would forgo a feeding tube, and 5 of 50 would forgo antibiotics. Five of 50 would forgo all four treatments, and 12 of 50 all but antibiotics. Spouses were significantly more likely to forgo treatment in the face of coma than for critical illness (P < .001). Spouses were more certain about decisions related to coma than to critical illness (P < .001), and there was a positive and significant correlation between certainty and comfort (P = .001). Those consenting to treatment were more comfortable than those forgoing treatment (for CPR and antibiotics P = .001). Spouses of patients with Stage 7 AD were more likely to forgo CPR than those with Stages 4 to 6 AD (P < .001). Only two of 50 spouses selected descriptors congruent with a purely substituted judgment standard of decision-making. An equal number of spouses rated patient quality of life as good, fair, or poor. For critical illness, the poorer the quality of life rating, the more likely the spouses were to forgo feeding tubes (P < .001). There was a trend for highly burdened spouses to consent to treatment. CONCLUSIONS: The results provide evidence that spouses of patients with AD anticipate forgoing life-sustaining treatments in the face of coma but are less sure about choices for critical illness. Although preliminary in nature, findings suggest that doctors, nurses, and social workers need to provide additional support to spouses choosing to forgo rather than consent to treatment and need to inquire as to what spouses perceive as the factors that are important to them in making a decision.

Advance Directives↗
PubMed1996

Osteolytic lesions as a presenting sign of acute nonlymphocytic leukemia.

Osteolytic lesions occur rarely in acute leukemia, especially in adults. We describe a patient with chronic myelomonocytic leukemia, in whom multiple osteolytic lesions were the presenting sign of the transformation into acute leukemia. Local irradiation to a painful lesion in the left hip resulted in transient but significant symptomatic relief with improved quality of life. We conclude that osteolytic lesions, although rare in adult acute leukemia, indicate an advanced disease state, but may respond to palliative local irradiation.

Aged↗
PubMed1996

Hippocampal formation size predicts declining memory performance in normal aging.

Hippocampal formation (HF) atrophy, although common in normal aging, has unknown clinical consequences. We used MRI to derive HF size measurements at baseline on 44 cognitively normal older adults entering a longitudinal study of memory function (mean age = 68.4 years, mean follow-up = 3.8 years). Only one subject became demented at follow-up. Multiple regression analyses controlling for age, gender, education, and diffuse cerebral atrophy revealed that HF size significantly predicted longitudinal change on memory tests previously found sensitive to decline in normal aging. These results indicate HF atrophy may be a risk factor for accelerated memory dysfunction in normal aging.

Aged↗
PubMed1996

Beneficial effect of granulocyte-colony stimulating factor in scleromyxoedema associated with severe idiopathic neutropenia.

The treatment of scleromyxoedema is notoriously difficult. We present a patient with long-standing diffuse scleromyxoedema associated with functional impairment who developed chronic idiopathic neutropenia complicated by recurrent life-threatening infections. Treatment with recombinant granulocyte--colony stimulating factor led to normalization of the neutrophil count, prevented further systemic infections, and unexpectedly was associated with a striking clinical improvement of her skin disorder and decrease in mucin deposition in the dermis.

Chronic Disease↗
PubMed1996

Anemia of cancer: pathogenesis and treatment with recombinant erythropoietin.

The anemia of malignancy is common and is related to several etiologic factors, a major one being relative erythropoietin (Epo) deficiency. Blood transfusions, the traditional therapy, provides a quick solution but is associated with complications. This was the rationale for recombinant human Epo (rHuEpo) in the treatment of anemia of cancer. Over the past few years, about 20 publications have reported the results of rHuEpo in the treatment of cancer-associated anemia in more than 850 patients with a variety of malignancies. In general, more than half of the patients responded with a significant increase in their hemoglobin level, a decrease in blood transfusion requirements, and an improved performance status and quality of life. About 4 weeks are required till the onset of effect. The hormone is well tolerated with minimal adverse effects and subcutaneous injections appear to be the preferred method of administration. Additional studies will hopefully answer several questions including optimal dosage and duration of treatment, Epo resistance, and the possibility of predicting the response.

Anemia, Aplastic↗
PubMed1995

Secondary myelodysplastic syndromes and acute leukemias.

Secondary myelodysplastic syndrome (sMDS) and secondary acute leukemia (sAL) are hematologic neoplasms occurring a few years following another primary malignancy, and are believed to be related to the chemotherapy used for the primary disease. Alkylating agents are considered to be more leukemogenic than other chemotherapeutic agents. Hodgkin's disease and multiple myeloma, among the hematologic neoplasms, and breast cancer among the solid tumors, are associated with this late complication more than other malignancies. The clinical picture is similar to primary MDS. However, the course is rapid, with early leukemic transformation and poor prognosis. since many sMDS patients are relatively young, it is reasonable to suggest an aggressive approach, i.e. bone-marrow transplantation (BMT) or antileukemic chemotherapy. The older patients may be offered low dose ara-c (LDAC), differentiating agents or clinical trials with growth factors. Even the responders survive no more than a few months.

Acute Disease↗
PubMed1995

Is it possible to improve the autopsy rate?

To improve the autopsy rate in a department of internal medicine, the method reported by Clayton and Sivak in 1992 was simplified and applied for a 12 month period, from January through December 1993. The basic principle of this method is involvement of the senior resident staff and supervision of the project by the head and deputy head of the department, on a daily basis. A simple form was designed for this purpose and was completed for each case. Results were compared with those between the same months in 1992. An increase in the autopsy rate from 1.8% in 1992 to 26.7% during the trial period in 1993 was noted.

Autopsy↗
PubMed1995

Hemorrhagic pleural effusion as a complication of chronic lymphocytic leukemia.

We report a case of hemorrhagic pleural effusion in a 59-year-old-man with chronic lymphocytic leukemia (CLL). The association between pleural effusion and CLL has been rarely reported and we believe that the pleural effusion probably reflected an advanced and refractory disease in our patient. Early detection of this complication is essential for appropriate therapy.

Antineoplastic Combined Chemotherapy Protocols↗