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Biomedical subjects

A Sawitsky

Publications and source records attributed to A Sawitsky.

At least 19 recordsLinked to original sources

Prevalence of HTLV-I-associated T-cell lymphoma.

In order to assess the prevalence rate of HTLV-1-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively. Significantly increased HTLV prevalence rates were observed among paid blood donors, African American health care clinic patients, Amerindians, recipients of HTLV-positive cellular blood products, intravenous drug users, sexual contacts and family members of HTLV-positive people, and patients with primary thrombocytosis and other-than-low-grade non-Hodgkin's lymphoma (NHL). Among some of these groups there were significant differences in the prevalence of HTLV-I versus HTLV-II. The eight HTLV-positive NHL patients all had mature, high-grade, CD4+ T-cell lymphomas with clonally integrated HTLV-I, for a prevalence of 4% among other-than-low-grade NHL patients. Seven of the eight died from their disease within 2 years despite treatment. Interestingly, two groups at risk for HTLV infection, namely needle stick victims and recipients of HTLV-infected and/or pooled plasma products, showed no evidence for infection. Significantly increased HIV-1 prevalence was observed among paid blood donors, African Americans, homosexuals, female prostitutes, hemophiliacs, and other-than-low-grade NHL patients. Only one patient was infected with HIV-2. Of the nine HIV-positive, other-than-low-grade NHL patients, seven HIV-1 positives had B-cell lymphomas, one HIV-1 positive had an HTLV-I-positive CD4+ T-cell lymphoma, and one infected with HIV-2 had a CD4+ T-cell lymphoma that was HTLV negative. The data indicate that HTLV-I lymphoma, while uncommon, is not necessarily rare among other-than-low-grade NHL cases in the United States and, given its poor prognosis, should probably be studied separately in clinical trials.

Black or African American↗

Coagulation abnormalities in patients with Gaucher's disease: effect of therapy.

Various coagulation defects have been associated with Gaucher's disease, including factor IX deficiency and acquired von Willebrand's disease (VWD). We performed repeated coagulation assays in 9 patients with Gaucher's disease over a period of 2 years. The prothrombin time (PT) and fibrinogen levels were normal in 8 of 9 patients, while the partial thromboplastin time (PTT) was abnormal in 5 of 9; all mixing PTT tests showed correction. Factor IX was normal repeatedly in the 7 of 7 patients tested. In contrast, factor XI was decreased in 3 of 9 patients assayed. Anticardiolipin (ACL) IgM was normal in all patients. ACL IgG was highly variable; levels were abnormal at least once in 6 of 8 patients, but were also normal at least once in 7 of 8 patients. Factor VIII was also quite variable: levels were decreased at least once in 4 of 9 patients, and normal at least once in 8 of 9 patients. Von Willebrand factor antigen (VWF Ag) studies were normal in 7 of 8 patients, but VWF activity was decreased at least once in 4 of 8 patients. In some patients, these problems could be overcome by specimen dilution. In ony 1 patient was VWF Ag decreased; this patient had a factor VIIIC level of 13% , and VWF activity of 18.7%. Coagulation assays performed before and after alglucerase administration failed to demonstrate any significant improvement in these assays, and neither was there a consistent improvement over the duration of therapy. We suggest that previously reported decreases in factor IX and VWF may be secondary to the interfering presence of increased cerebroside levels. Caution must be used in the interpretation of clotting assays in the patient with Gaucher's disease.

Antibodies, Anticardiolipin↗

Impaired interferon alpha response in hairy cell leukemia is corrected by therapy with 2-chloro-2'-deoxyadenosine: implications for susceptibility to opportunistic infections.

Patients with hairy cell leukemia (HCL) are susceptible to opportunistic intracellular infections, suggesting defects in cellular immunity. Prior studies have indicated an association between failure of IFN-alpha generation by peripheral blood mononuclear cells (MNC) and susceptibility to such infections. We here present results on IFN-alpha generation in HCL patients pre- and post-therapy. Prior to treatment with 2-chloro-2'-deoxyadenosine (CdA), MNC from 24 HCL patients with active disease produced little or not IFN-alpha (geometric mean < 40 IU/ml) compared with controls (n = 140, geometric mean 1730 IU/ml, p < 0.0005). After treatment with CdA, IFN-alpha generation was studied in 16 patients, with a geometric mean value of 650 IU/ml (p < 0.0005 compared with pre-CdA levels). The severe depression of IFN-alpha generation improved progressively following CdA therapy-induced clinical remission. We propose that deficiency of IFN-alpha production may play a role in the susceptibility to intracellular infections of patients with active HCL.

Adult↗

Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth.

We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B-CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B-cell growth and/or growth stimulation of the leukemic clone in B-CLL.

Antigens, CD↗

Hepatocellular carcinoma in a long-term survivor of acute lymphocytic leukemia.

Hepatocellular carcinoma (HCC) occurred in a 28-year-old woman treated for acute lymphocytic leukemia (ALL) with methotrexate (MTX) and 6-mercaptopurine (6-MP), off all therapy for 15 years, who was also heterozygous for alpha-1 antitrypsin (alpha-1 AT) deficiency. MTXD is responsible for the development of HCC in this patient. The literature concerning the incidence of HCC in patients treated with MTX and 6-MP and in alpha-1 antitrypsin deficiencies is reviewed.

Adult↗

Ultrasonic evaluation of the scrotum in lymphoproliferative disease.

Scrotal ultrasound examinations of 23 male adults and children with the diagnosis of lymphoproliferative disease (LPD) were performed. Diagnoses included acute lymphoblastic leukemia (ALL) (six patients); acute myelogenous leukemia (AML) (one patient); chronic lymphocytic leukemia (CLL) (nine patients); non-Hodgkin's lymphoma (four patients); Hodgkin's lymphoma (three patients). Sonography-biopsy correlation was 100% in identifying testicular infiltrates. Nine of ten patients with testicular involvement had bilateral disease. Six patients had nonpalpable disease correctly identified by sonography. Ultrasound has great potential value as a screening modality for testicular biopsy in ALL and for detecting subclinical or nonpalpable disease in adults with LPD.

Adolescent↗

A review of the prognostic role of cytogenetic, phenotypic, morphologic, and immune function characteristics in chronic lymphocytic leukemia.

Recent reports of successfully completed cytogenetic studies using polyclonal B-cell activators demonstrate that trisomy-12 and 14 q+ are the most frequently observed chromosomal abnormalities in B-cell chronic lymphocytic leukemia (CLL). It appears that when trisomy-12 is accompanied by yet another abnormality, the prognosis of patients is uniformly poor. Patients in early stages of CLL retain delayed hypersensitivity reactivity, while those in advanced stages are usually anergic. The lymphocytes from venous blood of patients with CLL appear to retain at least some ability to respond to stimulation with mitogens in early stages, whereas in advanced stages they show no response to mitogens. Serum immunoglobulin levels are normal in the early (0 and I) stages, are markedly decreased in the advanced (III and IV) stages, and are somewhat between these extremes in the intermediate (II) stage of CLL. Prolymphocytic leukemia and prolymphocytoid transformation of CLL are indicators of poor prognosis, while a morphological variant characterized by large granular lymphocyte is associated with good prognosis. At this time it is not possible to ascribe strong prognostic significance to phenotypic features of lymphocytes in B-CLL; however, studies currently in progress may soon provide important insights on this subject. We have reviewed the pertinent literature and we also present a summary of results from our laboratory.

Chromosome Aberrations↗

Chronic lymphocytic leukemia.

This article reviews, for the internist, recent advances in our understanding of the immunology and clinical characteristics of chronic lymphocytic leukemia (CLL). The method of treatment based on clinical staging of CLL and as practiced in the authors' clinic is detailed. It also provides an outline of possible investigation and therapy that may be expected in the coming years.

Antineoplastic Combined Chemotherapy Protocols↗

Changes in body composition of cancer patients following combined nutritional support.

The effects of combined nutritional support (parenteral, enteral, and oral) were measured in cancer patients unable to maintain normal alimentation. Changes in body composition were quantified by measurement of total body levels of nitrogen, potassium, water, and fat. The protein-calorie intake of the patients was also evaluated by dietary survey (4-day recall). Standard anthropometric and biochemical measurements for nutritional assessment were obtained for comparison. The dietary evaluation indicated that the dietary supplementation for all patients was more than adequate to meet their energy requirements. Almost all patients gained weight on the combined nutritional support regimens. Determination of body composition indicated that change in body weight was equal to the sum of the changes in body protein, total body water, and total body fat. The findings from the anthropometric nutrition indices (arm muscle circumference and triceps skinfold) were consistent with the results of the body composition study. Information on the nature of the tissue gained was obtained by comparison of body composition data with the ratio of protein:water:lean body mass for normal tissue. The mean gain of protein in the cancer patients was quite small (0.3-0.6 kg). The main change in body weight appeared to be the result of gains in body water and body fat. The total body nitrogen to potassium ratio served to define the extent of tissue anabolism following hyperalimentation. The ratio dropped in the cancer patients following hyperalimentation toward the value of the control subjects on ad libidum diets. The body compartment techniques described have demonstrated their usefulness in determining the effects of hyperalimentation on cancer patients.

Adipose Tissue↗

Biliary excretion of glycolipid in induced or inherited glucosylceramide lipidosis.

Metabolically inert L-[1-14C]glucosylceramide is stored predominantly in the liver after intravenous administration to mice. The half-time of this glycolipid analogue in the liver is 3.5 days and its clearance occurs predominantly via the bile. Within the limited number of Gaucher specimens available for examination very high levels of glucosylceramide were found in the bile of one patient and in the liver of two patients with biliary obstruction. The question of a possible relationship between biliary excretion of glycolipid and the pathogenesis of Gaucher's disease will require further studies.

Animals↗

Compartmental body composition of cancer patients by measurement of total body nitrogen, potassium, and water.

Quantitative measurement was made of body composition in patients with several forms of neoplastic disease. Total body nitrogen was determined by means of the prompt gamma neutron activation technique; total body potassium was measured with the use of a whole body counter. The mass and protein content of the muscle compartment and nonmuscle lean tissue were estimated by application of the technique of compartmental analysis. Total body water, determined simultaneously with the use of tritium label, provided a measure of lean body mass. From these data, the body fat can be inferred. The prompt gamma neutron activation and whole body counting techniques represent a considerable advance over the balance and radioisotope techniques used in earlier studies. The new techniques make possible sequential studies over prolonged periods of time with a considerable degree of accuracy. The loss of body weight by patients with solid tumors consisted primarily of the loss of muscle mass and body fat. Even in severe wasting, the patients appear to retain significant amounts of body fat. It is the skeletal muscle which is predominantly lost; the visceral life-supporting system is, to a considerable extent, spared. The nonmuscle tissue including the visceral fraction did not change in this study, and actually appeared to increase in size when comparison was made with the normal contrast population. The loss of total body water was slight in the cancer patients studied.

Adipose Tissue↗

Comparison of methods of estimating body fat in normal subjects and cancer patients.

Total body fat can be indirectly estimated by the following noninvasive techniques: determination of lean body mass by measurement of body potassium or body water, and determination of density by underwater weighing or by skinfold measurements. The measurement of total body nitrogen by neutron activation provides another technique for estimating lean body mass and hence body fat. The nitrogen measurement can also be combined with the measurement of total body potassium in a two compartment model of the lean body mass from which another estimate of body fat can be derived. All of the above techniques are subject to various errors and are based on a number of assumptions, some of which are incompletely validated. These techniques were applied to a population of normal subjects and to a group of cancer patients. The advantages and disadvantages of each method are discussed in terms of their ability to estimate total body fat.

Adipose Tissue↗

Bone marrow biopsy and clinical staging in chronic lymphocytic leukemia.

We have examined the value of bone marrow biopsy histopathology in chronic lymphocytic leukemia (CLL). Cases involving a pattern of interstitial, nodular, or mixed interstitial plus nodular infiltration of lymphocytes were clinically similar and manifested a more benign course. These patterns correlated with the clinical Stages 0, I, and II. However, cases involving a pattern of diffuse or mixed diffuse plus nodular infiltration of lymphocytes formed a clinical group with a more rapidly progressive course and these patterns correlated with clinical Stages III and IV. Other measurements, e.g., calculation of the percentage of lymphatic tissue in the bone marrow biopsy specimen and of the ratio of the percentage of lymphatic tissue in marrow to the peripheral blood lymphocyte count, were found to be cumbersome to perform and of no additional value to clinical staging in prognosis indication in CLL.

Biopsy↗

Mosaicism of red cell ABO type without recognizable cause.

A 19-year old woman has been found whose red cells are a mixture of groups A1B (60%) and A1 (40%). Tests for many other genetic markers show no other evidence of mosaicism. She is not a twin and her parents and a sib are of normal ABO type. The cause of her dual population of red cells cannot be established, but may be an effect of somatic crossing over or mutation.

ABO Blood-Group System↗