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Biomedical subjects

M Mittelman

Publications and source records attributed to M Mittelman.

At least 19 recordsLinked to original sources

Splenic lymphoma presenting as warm autoimmune hemolytic anemia associated with pure red cell aplasia.

BACKGROUND AND OBJECTIVE: Warm autoimmune hemolytic anemia (AIHA) is a condition in which peripheral red blood cell (RBC) destruction is induced by the presence of an autoantibody. Pure red cell aplasia (PRCA) represents an isolated process of decreased erythropoiesis. The combination of both is quite rare, with a very poor prognosis. We describe a patient with isolated splenic lymphoma whose presentation was a combination of AIHA and PRCA. The patient was resistant to all treatment. MATERIALS AND METHODS: Erythroid colony assays were performed, in order to compare the effect of the patient's serum on colonies with that of a normal control. RESULTS: The patient's serum significantly suppressed normal erythroid colony growth. A red cell eluate revealed the presence of a warm autoantibody. CONCLUSIONS: The patient's serum contained warm autoantibody responsible for peripheral RBC destruction and a humoral factor, perhaps the warm autoantibody, which suppressed bone marrow erythropoiesis. Establishing an early diagnosis, and treatment of the underlying disease might result in a better prognosis.

Anemia, Hemolytic, Autoimmune↗

Severe amyloidosis with mild multiple myeloma--an unusual course.

Amyloidosis may be primary or myeloma-associated. Skeletal lesions and the percentage of bone marrow plasma cells (<10% in primary, >20% in myeloma) account for the major differences between the two varieties. In the literature there are rare cases of primary amyloidosis presenting without myeloma and followed by development of myelomatous manifestations. Usually, the primary disease (i.e. the myeloma) is advanced, when amyloidosis is diagnosed. We describe a patient who had presented with a severe and progressive systemic amyloidosis and was diagnosed later to have a mild light chain myeloma. Aggressive treatment with melphalan, prednisone and colchicine resulted in a temporary partial remission, followed by a rapid downhill course, and the patient's death. The point of relatively mild myeloma following a rapidly progressive course of advanced amyloidosis is emphasized. Awareness of the possibility of such a combination may lead to early diagnosis, a more aggressive or novel therapeutic approach and, possibly, to a better prognosis.

Amyloidosis↗

The incidence of pseudothrombocytopenia in automatic blood analyzers.

UNLABELLED: The aim of the present work was to undertake an assessment of the incidence of pseudothrombocytopenia (PTCP) in patients referred for evaluation of thrombocytopenia in an outpatient hematology clinic. METHODS: Prospective assessment of 60 consecutive cases with platelet count < 100 x 10(9)/l in a hematology clinic during a 2-year period. RESULTS: PTCP was the second most common cause for low platelet count, with an incidence of 17%. Platelet count of patients with PTCP at presentation was 42 +/- 22 x 10(9)/l, and when re-analyzed on fresh samples, 208 +/- 39 x 10(9)/l. The relatively high prevalence of pseudothrombocytopenia in our series was due to a lack of microscopic inspection of the blood smear in the primary care laboratories and considerable delay in sample processing. CONCLUSIONS: PTCP should be considered in the assessment of low platelet count. While decreasing the transfer time of blood specimens may decrease PTCP incidence, microscopic inspection of the blood smear may avoid erroneous diagnosis of thrombocytopenia.

Adult↗

Platelet function in the myelodysplastic syndromes.

Bleeding in myelodysplastic syndromes (MDS) is often related to thrombocytopenia. However, because MDS is a stem cell disorder, it is conceivable that platelet function (PF) abnormalities may play a role as well. A few studies have been reported, mainly with platelet aggregation (PA). A summary of the information discloses that about 68 MDS patients have been studied. Despite some conflicting data, it can be concluded that PA defects are quite common in MDS. About 75% of MDS patients demonstrated reduced PA with epinephrine, followed by decreased PA with arachidonic acid (54%), ADP (46%), collagen (43%), and ristocetin (22%). Several other PFs were studied, but the data require caution in interpretation. Despite the relatively high incidence of platelet dysfunction, bleeding in MDS patients is uncommon, with episodes tending to be mild, although recurrent. Nevertheless, some correlation between PA abnormalities and the tendency to bleed has been suggested. As patients demonstrate more PA defects, they tend to bleed more. Some authors suggest that PF studies may assist in diagnosing tough cases of MDS, as well as serving as prognostic markers. A large-scale study testing PF in a large number of MDS patients is required and is expected.

Blood Coagulation Disorders↗

Chronic relapsing thrombocytopenic purpura with severe neurological manifestations and full recovery.

Neurological complications in thrombotic thrombocytopenic purpura (TTP) are associated with poor prognosis and/or permanent damage. We report a young woman in whom the diagnosis of TTP was difficult because cardinal manifestations were absent at presentation. The patient relapsed, showing severe and dramatic neurological manifestations, including coma. She was treated with multiple therapeutic modalities and recovered fully with no neurological sequelae. The difficulties involved in the management of chronic relapsing TTP are discussed. In the absence of clear guidelines, patients are still subjected to different treatment modalities according to the personal opinions and approaches of physicians. Clearly, well-controlled clinical trials to address this problem are required.

Adult↗

Effect of nutrient composition on the in vitro growth of urogenital lactobacilli and uropathogens.

Previous clinical studies have shown that nutrients and probiotic agents can alter the composition of the vaginal flora. The present in vitro study has shown that uropathogens have a growth advantage over lactobacilli, but potentially there are natural substances that could be applied vaginally to stimulate lactobacilli growth to the detriment of the pathogens. When chemically defined medium representative of vaginal fluid at pH 5.5 was supplemented with skim milk, it acted as a better substrate for Lactobacillus rhamnosus GR-1 than for uropathogenic bacteria and Candida albicans. Lactobacillus MRS medium, even at pH 4.5, supports the growth of pathogens, but when supplemented with ascorbic acid or EDTA, Lactobacillus growth was significantly higher. When L. rhamnosus GR-1 was coincubated in a combined nutrient composition of vitamins and lactose, it survived better than Escherichia coli and Enterococcus faecalis. These in vitro results provide a basis for testing nutritional supplements to alter the urogenital flora in an attempt to enhance restoration and maintenance of a normal disease-free state.

Animals↗

Interferon-induced vasospasm in chronic myeloid leukaemia.

The role of interferon (IFN) in the treatment of chronic myeloid leukaemia (CML) has been established. Many adverse effects have been reported, but vasospasm has been extremely rare. We report 2 CML patients who developed such complications. A 56-year-old female had been on IFN for 3 years with haematological and cytogenetic remission, when she developed an anginal syndrome followed by acute ischaemia. Coronary catheterization revealed normal arteries. After discontinuation of IFN her cardiac complaints disappeared and she needed no medication. A 61-year-old patient had been on IFN for 1 year when he presented with Raynaud's phenomenon. No evidence of collagen vascular disease could be documented. IFN discontinuation and intravenous administration of iloprost (a prostacyclin analogue) resulted in the disappearance of the vascular complications. IFN appears to have a beneficial effect on the course and prognosis of CML. However, we have to be aware of the potential complications and adverse effects which can be related to IFN. Neither our experience nor the literature provides convincing recommendations regarding the management of such patients. We suggest proceeding with IFN at lower doses, especially in those who have achieved a cytogenetic response, as our first patient.

Cardiac Catheterization↗

Total navy recruit health: making our sailors fit for the fleet.

Naval Hospital Great Lakes, Branch Medical Clinic, Recruit Training Command is the Navy's only recruit inprocessing point in the country. The clinic will medically inprocess approximately 54,000 new Navy recruits this year. In fiscal year 1995, the clinic inprocessed approximately 44,000 recruits, 35,000 males and 9,000 females. The Navy Medical Department is very concerned about total Navy recruit health. This includes a check on the present state of health of all sailors and teaching sailors how to stay healthy and take care of themselves during their naval careers. Navy medicine is also an integral part of the recruit training experience. Recruit training at Great Lakes is 9 weeks in duration. This article will describe the Navy's recruit medical inprocessing procedure to include the Sailor's Health Inventory Program, the Navy/Air Force Medical Entrance Test, immunizations, optometry, audiology, wellness education, gynecological examinations, medical assessment, and laboratory tests.

Female↗

Granisetron and ondansetron for chemotherapy-related nausea and vomiting.

The efficacy of granisetron and ondansetron, two serotonin antagonists, as antiemetic agents was studied and compared in the first 24 h follow, by chemotherapy administration. Sixty cancer patients took part in this randomized prospective study. The patients were categorized according to the chemotherapy which was administered. Patients in group A received combinations including the highly emetogenic agents, cisplatinum or adriamycin, patients in group B received regimens which included neither of these agents. Both serotonin antagonists were highly effective, only 9 (16%) out of 58 patients suffered from vomiting, 7 (25%) of the patients on ondansetron and 2 (7%) on granisetron. Splitting the patients into both groups supported the above results. In group A (adriamycin-cisplatinum) only 7 patients (22%) reported vomiting, 5 (33%) on ondansetron vs 2 (12%) on granisetron. In group B, only 2 patients (8%) suffered from vomiting, both patients (15%) on ondansetron while no vomiting was seen in the granisetron patients. Similar results were obtained in preventing nausea in these patients. We conclude that both serotonin antagonists are effective in preventing nausea and vomiting in patients receiving chemotherapy. In all groups tested this study granisetron appeared to be superior, although, this difference failed to reach statistical significance due to the small number of patients analyzed. However, there was no difference in cost effectiveness between the regimens.

Antiemetics↗

The two common mutations causing factor XI deficiency in Jews stem from distinct founders: one of ancient Middle Eastern origin and another of more recent European origin.

Previous studies showed that factor XI (FXI) deficiency commonly observed in Ashkenazi Jews is caused by two similarly frequent mutations, type II (Glu117stop) and type III (Phe283Leu) with allele frequencies of 0.0217 and 0.0254, respectively. In Iraqi Jews, who represent the ancient gene pool of Jews, only the type II mutation was observed with an allele frequency of 0.0167. In this study we sought founder effects for each mutation by examination of four FXI gene polymorphisms enabling haplotype analysis in affected Jewish patients of Ashkenazi, Iraqi, and other origins and in Arab patients. Initial population surveys of 387 Middle Eastern Jews (excluding Iraqi Jews), 560 North African/Sephardic Jews, and 382 Arabs revealed allele frequencies for the type II mutation of 0.0026, 0.0027, and 0.0065, respectively. In contrast, the type III mutation was not detected in any of these populations. All 60 independent chromosomes bearing the type III mutation were solely observed in Ashkenazi Jewish patients and were characterized by a relatively rare haplotype. All 103 independent chromosomes bearing the type II mutation in patients of Ashkenazi, Iraqi, Yemenite, Syrian, and Moroccan Jewish origin and of Arab origin were characterized by another distinct haplotype that was rare among normal Ashkenazi Jewish, Iraqi Jewish, and Arab chromosomes. These findings constitute the first example of a mutation common to Ashkenazi Jews, non-Ashkenazi Jews, and Arabs and are consistent with the origin of type II mutation in a founder before the divergence of the major segments of Jews. Our findings also indicate that the type III mutation arose more recently in an Ashkenazi Jewish individual.

Africa, Northern↗

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↗

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↗

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↗

[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↗

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↗

[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↗