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Biomedical subjects

Deborah Rund

Publications and source records attributed to Deborah Rund.

16 recordsLinked to original sources

Thrombocytosis accompanying urinary tract infection suggests obstruction or abscess.

OBJECTIVE: Reactive thrombocytosis can be found in patients with different types of infections, including upper urinary tract infection (UTI). In this study, we determined whether thrombocytosis in patients with upper UTI is a random phenomenon or is related to complications associated with the UTI. METHODS: We reviewed the charts of patients admitted to the urology department with a diagnosis of upper UTI and thrombocytosis (platelet count >500 x 10(9)/L) in the years 1991 to 2003 (study group). Patients admitted to the urology department in the year 2003 with a diagnosis of upper UTI without thrombocytosis served as the control group. RESULTS: The study group consisted of 83 patients admitted to the urology department with a diagnosis of upper UTI and thrombocytosis (mean platelet count, 593 x 10(9)/L; SD, 88; range, 501-949). The control group consisted of 99 patients. An obstructed kidney was found in 54 patients (65%) of the study group and in 18 patients (18%) of the control group (P < .00001). Perinephric abscess was found in 7 patients (8%) in the study group compared with none in the control group (P < .003). The positive predictive value of thrombocytosis for kidney obstruction or abscess in patients with upper UTI was 71%. Nephrectomy of a nonfunctioning infected kidney was required in 6 patients of the study group (7%) and 2 of the control group (P = .14). In 26 patients (31%) of the study group, the finding of thrombocytosis preceded the diagnosis of the complication (by a median period of 3 days). In these patients, thrombocytosis was essentially an early marker for the complication. CONCLUSIONS: Thrombocytosis in a patient with upper UTI is not a random phenomenon. It is a marker of kidney obstruction or perinephric abscess. The finding of thrombocytosis in a patient with upper UTI should alert the attending physician to actively search for these complications. Cross-sectional imaging study (abdominal ultrasonography or computed tomography) should be performed.

Abscess↗

Postoperative thrombocytosis as a marker for complications after urologic surgery.

OBJECTIVE: To determine whether thrombocytosis after urologic surgery is a random phenomenon or if it is related to postoperative complications. MATERIAL AND METHODS: We evaluated the postoperative course of patients who had a normal platelet count before surgery and developed significant thrombocytosis (platelet count> 500 x 10(9)/l) after surgery during the years 1991-2003. The rate of postoperative complications was compared among patients who did and did not develop thrombocytosis for the three commonest surgical procedures associated with the condition (radical cystectomy, percutaneous nephrolithotripsy and nephrectomy). RESULTS: A total of 179 patients developed thrombocytosis (mean+/-SD platelet count 580+/-105 x 10(9)/l; range 501-1,390 x 10(9)/l) after a mean of 13.6 days (SD 14.7 days) following surgery. In 90% of these patients, postoperative complications were diagnosed. The most frequent complications were as follows: urosepsis, n = 49 (27%); hemorrhage, n = 37 (21%); and thromboembolism, n = 15 (8.4%). These complications were diagnosed by means of clinical examination in 114 cases (64%), CT in 31 (17%), Doppler ultrasound in seven (4%) and other diagnostic modalities in nine. In 18 patients (10%), no apparent complication was diagnosed. The rate of postoperative complications was significantly higher among patients who developed thrombocytosis after surgery compared to those who did not (p < 0.00001). In 63 patients (35%), the finding of thrombocytosis preceded the diagnosis of the complication (by a median period of 5 days). In these patients, thrombocytosis was essentially an early marker for the impending complication. CONCLUSIONS: Postoperative thrombocytosis is not a random phenomenon. It is a serious sign that should not be ignored. Septic and thromboembolic complications should be actively sought by means of thorough clinical evaluation. CT of the abdomen should be considered in appropriate clinical settings. The timing of thrombocytosis and the pathologic spectrum of diseases demonstrated by patients with it justify classifying it as a marker of the subacute phase.

Adolescent↗

Severe infections in thalassaemic patients: prevalence and predisposing factors.

The incidence of infections among patients with thalassaemia and the role of risk factors for infection are uncertain. We studied the occurrence of infections necessitating hospitalisation in 92 homozygous beta-thalassaemia patients who had been followed longitudinally for decades, and investigated the role of potential risk factors for these infections. Pneumonia accounted for 26% of the infections and fever of unknown origin for 14%. Staphylococcus aureus was the major pathogen possibly related to injections associated with intensive chelation with deferoxamine. There was a significant increase in the rate of infection over time, notably after 15 years. Splenectomy correlated with the incidence of infection (P < 0.001) without being confounded by other variables and with highest frequencies of infections present after 10 years. A direct correlation between iron overload and infection was evident only before the initiation of iron-chelating treatment (P < 0.01). Following initiation of deferoxamine, paradoxically, the infection rate increased (P = 0.046). The combination of splenectomy and deferoxamine treatment was associated with the highest adjusted infection rate. Parathyroid dysfunction and glucose-6-phosphate dehydrogenase deficiency were significantly associated with infection (P = 0.02 and P = 0.04 respectively). The infection rate in thalassaemia is affected mainly by the duration of the disease and is increased by splenectomy and, in the long term, by treatment with deferoxamine.

Adolescent↗

The frequencies of NAD(P)H quinone oxidoreductase (NQO1) variant allele in Israeli ethnic groups and the relationship of NQO1*2 to adult acute myeloid leukemia in Israeli patients.

NAD(P)H:quinone oxidoreductase (NQO1) detoxifies quinones. The NQO1*2 variant enzyme (codon 609 C-->T, encoding a proline to serine substitution) with greatly reduced activity has been reported to predispose to acute myeloid leukemia (AML). Our aim was to examine the relationship between NQO1*2 and AML in Israeli patients. We analyzed for NQO1*2 in 262 adult Israeli patients with de novo AML and 688 controls of the same ethnic groups (Arabs, and Caucasian and Ethiopian Jews). Our analysis showed significant differences in the frequencies of NQO1*2 by ethnic group (p=0.000068). However, NQO1*2 frequencies did not differ between AML patients and controls. Karyotype was not found to be associated with NQO1*2. In Israeli patients, NQO1*2 does not predispose to de novo AML.

Acute Disease↗

Beta-thalassemia.

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Antioxidants↗

Myocardial infarction in a patient with beta-thalassemia major: first report.

Thalassemia is the most common hereditary anemia throughout the world. Survival in its most severe long-term form, beta-thalassemia major, has significantly risen in the last decades. Cardiac morbidity-heart failure and dysrhythmias-is still the most common cause of mortality in these patients. We describe herein a case of myocardial infarction with normal coronary arteries in a 48-year-old patient with beta-thalassemia and no other recognized risk factors for coronary artery disease. Thromboembolic phenomena, a known situation in these patients, occur at a frequency of 4-5%. However, as far as we know, this is the first report in the literature of myocardial infarction in association with beta-thalassemia. With the notable improvement in the life expectancy of thalassemia patients, ischemic heart disease may become an important complication encountered in these patients.

Electrocardiography↗

Role of open incisional biopsy in parotid tumors.

OBJECTIVE: Parotid gland enlargement due to diffuse pathologic processes represents a diagnostic challenge for the surgeon. In such cases, fine-needle aspiration is inconclusive and superficial parotidectomy is usually performed. MATERIAL AND METHODS: The authors treated eight patients who underwent open incisional biopsy of the parotid gland with continuous monitoring of the facial nerve. RESULTS: In all cases, fine-needle aspiration cytology did not provide a definitive diagnosis while open incisional biopsy provided an accurate diagnosis of a lymphoproliferative disorder, with no operative complications. CONCLUSION: In certain infiltrative parotid diseases such as lymphoepithelial or lymphoproliferative diseases, when fine-needle aspiration biopsy is insufficient as tissue architecture is an important component of the pathological diagnosis, an open incisional biopsy can be considered. This procedure can provide an accurate histological diagnosis while avoiding superficial parotidectomy.

Adult↗

Therapy-related leukemia and myelodysplasia: evolving concepts of pathogenesis and treatment.

Therapy-related leukemia and therapy-related myelodysplasia (t-AML/MDS) are serious and increasingly frequent complications of cytotoxic chemotherapy and/or radiotherapy. Two syndromes can be distinguished, one of which has a long latency (5-7 years or more) and is seen following alkylating agents, frequently with an antecedent dysplastic phase. The other has a short latency period (1-3 years), no antecedent dysplastic phase, and is characteristically seen following topoisomerase II inhibitors. Chromosomal abnormalities can confirm t-leuk/MDS and are predictive of poor prognosis, particularly those involving gains and losses of chromosome 7. There is no standard therapy for t-AML/MDS. This review concentrates on the various treatment approaches for t-AML/MDS. Treatment can be aggressive, with curative intent, particularly for patients who are young with no end-organ damage from the prior malignancy or chemotherapy. Various chemotherapy regimens have been designed to overcome the chemoresistance which is generally characteristic of these syndromes. Bone marrow transplantation offers the best chance for cure, and both myeloablative and nonmyeloablative protocols have been designed. Low dose chemotherapy is an option for patients not able to withstand traditional curative regimens and supportive care is a legitimate option for elderly or infirm patients. Multicenter studies are urgently needed to provide data on which clearcut treatment guidelines can be based, taking into account the patient's age, disease status and risk factors.

Antineoplastic Agents↗

In vitro-packaged SV40 pseudovirions as highly efficient vectors for gene transfer.

A procedure for in vitro packaging of plasmid DNA in recombinant SV40 capsid proteins was developed by Sandalon et al. (1997). Here, we report the highly efficient transduction into different human, murine and monkey cell lines using a scaled-up protocol for producing SV40 pseudovirions, packaged in vitro, carrying the human multidrug-resistance gene MDR1 encoding P-glycoprotein (P-gp) or the green fluorescent protein reporter gene (GFP) under control of SV40 and cytomegalovirus (CMV) promoters. The percentage of expressing cells was proportional to the number of transducing particles, with close to 100% of cells transduced at optimal ratios of transducing particles to cells. The ability to confer multidrug resistance was evaluated by measuring dye efflux and cell-surface expression in infected cells. The relative level of expression of P-gp driven by the different promoters varied among different cell lines. In human lymphoblastoid cells, which express high levels of major histocompatibility complex (MHC) class I (a surface receptor for SV40), constructs that carry an intron yield the highest expression. Our experiments further demonstrate that MDR1 and GFP expression driven by these promoters is transient; however, transduced cells remain MDR1-positive if selected in colchicine. Thus, the SV40 vectors are well suited to situations in which only short-term expression is required or expression is selected, such as for bone marrow protection during chemotherapy.

Animals↗

Acute myocardial infarction as the presenting symptom of acute myeloblastic leukemia with extreme hyperleukocytosis.

This case report deals with an unusual leukostatic complication in a 56-year-old woman with acute myeloblastic leukemia (AML) and extreme hyperleukocytosis (316 x 10(9)/L) who presented with acute myocardial infarction (MI). After leukopheresis the patient achieved hemodynamic stabilization and rapid neurologic recovery of encephalopathy that had also developed after the infarction. Considering the central role of WBC in the remodeling of post MI myocardial tissue, it was obvious that administration of chemotherapy with its subsequent inevitable pancytopenia could impose an increased risk for further cardiac complications including myocardial rupture. Nevertheless, cytarabine-based induction chemotherapy was initiated 3 days after admission, and she achieved prolonged complete remission. Coronary angiography disclosed segmental atherosclerosis, but the only significant obstruction was in the right coronary artery. The patient died with relapsed leukemia 7 years later without recurrence of any cardiac symptoms or signs. Autopsy disclosed segmental coronary atherosclerosis involving the LAD (60% obstruction), suggesting that atherosclerosis was a predisposing risk factor. Additional compromise to blood perfusion due to leukostasis had led to this unusual complication of AML involving a major vessel. This is the first documented case of leukostasis causing coronary artery occlusion as well as the first report of successful induction chemotherapy for AML during a myocardial infarction.

Aminoglycosides↗

The beta+-IVS-I-6 (T-->C) mutation accounts for half of the thalassemia chromosomes in the Palestinian populations of the mountain regions.

A study of the spectrum of beta-thalassemia mutations in the southern part of the West Bank of the Palestinian Authority revealed the presence of 10 different beta-globin mutations. The study included 41 patients and 54 carriers of beta-thalassemia and sickle cell anemia. The spectrum of mutations observed was typically Mediterranean. However, their relative frequencies was unique. The predominant allele was IVS-I-6 (T-->C), with an exceptionally high frequency of 48.5% for this mutation. The homozygous IVS-I-6 patients had widely variable clinical presentations, from typical transfusion-dependent thalassemia major to non-transfusion-dependent thalassemia intermedia phenotype. Since it is so widespread in these West Bank populations, the IVS-I-6 mutation may date back to ancient times. The nonsense mutation at codon 37 (G-->A) was found at a relatively high frequency of 11.3%, supporting the hypothesis that it originated in this region. The other mutations, at decreasing frequencies ranging from 9.5-1.5%, were: IVS-I-110 (G-->A), frameshift codon 5 (- CT), IVS-I-1 (G-->A), IVS-II-1 (G-->A), Hb S [beta6(A3)Glu-->Val], frameshift codons 8/9 (+G), codon 39 (C-->T), and -30 (T-->A). Our findings will improve health care for the Palestinian population, and also has implications for the study of the origin and spread of thalassemia in the Middle East.

Adolescent↗

One year experience with a low density lipoprotein apheresis system.

BACKGROUND: Low density lipoprotein apheresis is used as a complementary method for treating hypercholesterolemic patients who cannot reach target LDL-cholesterol levels on conventional dietary and drug treatment. The DALI system (direct absorption of lipoproteins) is the only extracorporeal LDL-removing system compatible with whole blood. OBJECTIVE: To describe our one year experience using the DALI system. METHODS: LDL apheresis was used in 13 patients due to inability to reach target LDL-C levels on conventional treatment. They included seven patients with familial hypercholesterolemia, three who had adverse reactions to statins, and three patients with ischemic heart disease who did not reach LDL-C target level on medical treatment. RESULTS: The average triglyceride, total cholesterol, high density lipoprotein-C and LDL-C levels before and after treatment in all patients were: 170 +/- 113 vs. 124 +/- 91, 269 +/- 74 vs. 132 +/- 48, 42 +/- 8 vs. 37 +/- 7.9, and 196 +/- 77 vs. 80 +/- 52 mg/dl, respectively. Comparing the results of a subgroup of seven patients who had previously been treated with plasma exchange, it is noteworthy that while the reduction in triglyceride, total cholesterol and LDL-C are comparable, the effect on HDL-C concentration was less apparent: from an average of 39.7 +/- 8.7 and 23 +/- 5.7 mg/dl before and after plasma exchange to an average of 43.9 +/- 8.1 and 38.4 +/- 7 mg/dl before and after LDL apheresis, respectively. Five patients developed treatment-related adverse events: three experienced allergic reactions manifested as shortness of breath, urticaria and facial flushing; one patient developed rhabdomyolysis, an adverse reaction that was not reported previously as a result of LDL apheresis; and one patient had myopathy with back pain. All untoward effects occurred during the first few treatment sessions. CONCLUSIONS: LDL apheresis using the DALI system is highly efficacious for the treatment of hypercholesterolemia. It is associated with a significant number of side effects occurring during the first treatment sessions. In patients not experiencing adverse effects in the early treatment period, it is well tolerated and can provide remarkable clinical benefit even after short-term therapy.

Adolescent↗

An unexpectedly high frequency of heterozygosity for alpha-thalassemia in Ashkenazi Jews.

alpha-Thalassemia is among the world's most common single gene disorders, which is most prevalent in the malaria belt. This geographic distribution has been attributed to a selective advantage of heterozygotes against this disease. Unexpectedly, we have found a high frequency of heterozygosity for deletional alpha-thalassemia (-alpha3.7) in Ashkenazi Jews (carrier frequency of 7.9%, allele frequency of 0.04). This population has resided in temperate climates for many centuries and was therefore not subjected to malarial selection pressure. In comparison, heterozygosity for beta-thalassemia, which is highly subject to malarial selection pressure, is very low (estimated <0.1%) in this group. It is possible that founder effect and genetic drift have contributed to the high frequency of deletional alpha-thalassemia in Ashkenazim, as may occur in closed populations. Alternatively, we hypothesize that positive selection pressure for an as yet unknown linked allele on chromosome 16 may be a significant factor leading to this high frequency.

Founder Effect↗