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HLA and adult T cell leukaemia: HLA-linked genes controlling susceptibility to human T cell leukaemia virus type I.

HLA antigens of patients with adult T cell leukaemia (ATL), T cell malignant lymphoma (T-ML), and healthy carriers of human T cell leukaemia virus type I (HTLV-I) were investigated in an endemic area of ATL in Japan. Sixty-two patients with ATL were subdivided into three groups based on their clinical features, including two unclassified patients; 36 acute type, 10 chronic type, and 14 smouldering type. The frequency of HLA-Bw62 was significantly increased in acute ATL, compared with control (Pc less than 0.0002). Increased frequency of HLA-DQw3 was observed in patients with ATL, T-ML positive for the antibody to HTLV-I (Ab-positive), and Ab-positive healthy carriers, compared with control (Pc less than 0.001, Pc less than 0.01 and Pc less than 0.0001, respectively). In addition, class I HLA antigens of peripheral lymphocytes of patients with ATL, especially acute ATL, showed altered expression, either extra antigens or decreased antigens. Analysis of 21 families, where more than two members were Ab-positive, showed that there was no linkage between the HLA complex and susceptibility to the virus infection. In 44 couples, in which either or both spouses were Ab-positive, no association with class I HLA antigens was found in either Ab-positive spouses or Ab-negative spouses. These findings might indicate that one class II HLA-linked gene controlled susceptibility to HTLV-I infection, and another class I HLA-linked gene exerted an influence on the clinical course of ATL.

Antibodies, Viral↗

Preleukemic state of adult T cell leukemia: abnormal T lymphocytosis induced by human adult T cell leukemia-lymphoma virus.

We report the clinical, hematologic, and immunologic features of 18 preleukemic adult T cell leukemia (pre-ATL) cases with abnormal T lymphocytosis induced by human adult T cell leukemia-lymphoma virus (HTLV/ATLV). The patients were from the Nagasaki district, which is one of the most endemic areas of ATL in Japan. Pre-ATL is a subclinical T cell abnormality differing from ATL. It is characterized by an insidious onset and appearance of abnormal T lymphocytes (10% to 40%) in the peripheral blood without clinical symptoms except for a few cases transiently presenting fever, skin eruptions, and slight lymphadenopathies. Most abnormal T lymphocytes were small and mature with incised or lobulated nuclei and formed E rosettes with sheep RBCs. Virologic and biomolecular analysis revealed that all cases were infected with HTLV, and proviral DNA was integrated in host lymphocytes from 12 of the 14 cases examined. Furthermore, the lymphocyte populations, including abnormal T lymphocytes, were monoclonal with respect to the site of the provirus integration. Abnormal T lymphocytosis persisted from one to more than seven years in six cases, three of which developed ATL after a one- to five-year pre-ATL stage, whereas abnormal T lymphocytes spontaneously decreased in the other seven patients. However, HTLV-infected monoclonal lymphocytes were detected in four cases examined, even after most of the abnormal T lymphocytes had disappeared. Moreover, the same clonally provirus-integrated lymphocytes persisted in two of four cases not only during the course of abnormal lymphocytosis, but also in the subsequent almost-normal blood. These results indicate that the majority of the cases were in a pre-ATL state with a potential to develop ATL.

Adult↗

Statistical analyses of clinico-pathological, virological and epidemiological data on lymphoid malignancies with special reference to adult T-cell leukemia/lymphoma: a report of the second nationwide study of Japan. The T- and B-Cell Malignancy Study Group.

In the present nationwide survey, 1,040 new cases of lymphoid malignancy, in most of which expression of cell surface markers had been determined, and 243 controls for a case-control study on adult T-cell leukemia/lymphoma (ATL) and other types of lymphoid malignancies were enrolled during the two years (1982-84) from 24 institutions throughout Japan. Among the 1,040 cases, 197 cases of ATL, 183 cases of T-cell lymphoma and 236 cases of non T-cell lymphoma were used in the detailed analysis of the clinico-pathological and epidemiological findings. Furthermore, 66 cases of ATL and 174 cases of other lymphoid malignancies were used for case-control analysis. In order to standardize the clinico-pathological classification throughout Japan, 20 hematologists and 12 pathologists met once a year and made the final consensus diagnosis in each case of lymphoid malignancy. Five hundred cases of non-Hodgkin's lymphoma were examined for antibody to ATL-associated antigen (ATLA). Clinico-pathological and epidemiological features for these cases were compared according to their anti-ATLA antibody status. The new results obtained from this survey are as follows: All of the patients with ATL in Kyushu had anti-ATLA antibody, but several patients with ATL in other districts had no anti-ATLA antibody, suggesting that there was no association with ATL virus (ATLV) infection in these cases. There was a difference in the histopathological patterns in non-Hodgkin's lymphoma between Kyushu and the other districts, which was due to the difference in distribution of the ATLV-associated lymphoid malignancies, namely ATL, in each area. The histopathological distribution in anti-ATLA negative cases in the Kyushu district was almost the same as that in the other districts.

Adolescent↗

Abnormal expression of interleukin-2 receptor (Tac antigen) in adult T-cell leukemia.

Human T-cell leukemia/lymphoma virus type I(HTLV-I) infection appears to be closely associated with the leukemogenesis of adult T-cell leukemia (ATL), although its mechanism remains unclear. Since our previous report that leukemic cells from patients with ATL expressed Tac antigen (Ag) (interleukin-2 (IL-2) receptor) on their cell surface, we have been studying IL-2 receptors on ATL leukemic cells to see whether they are different from normal IL-2 receptors and whether they play a role in the neoplastic growth of ATL cells. Peripheral blood leukemic cells from 35 patients with ATL expressed IL-2 receptors which were detected by anti-Tac monoclonal antibody when examined immediately after the separation of cells or after culture for 24 or 48 hr. The number of anti-Tac binding sites ranged from 4,300 to 11,400 in fresh cells and from 6,100 to 96,000/cell in short term cultured leukemic cells, whereas phytohemagglutinin-P(PHA-P)-stimulated normal T cells exhibited 7,000 to 35,000 anti-Tac binding sites/cell. HTLV-I-infected cell lines such as MT-1 and HUT-102 expressed a markedly enhanced number of Tac Ag molecules. Leukemic cells from 15 ATL patients showed no or very poor proliferative response to various concentrations of IL-2, although they expressed Tac Ag. Radiolabeled IL-2 binding experiments revealed that ATL leukemic cells could bind IL-2 although the number of IL-2 binding sites was much less than that of anti-Tac binding sites. IL-2 receptors on ATL cells, unlike normal activated T cells, were not modulated (down-regulated) by anti-Tac antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Surface↗

Characterization of anti-treponemal lymphotoxin from lymphocytes of syphilitic rabbits.

The effect of various treatments on the activity of anti-treponemal lymphotoxin (ATL) produced by lymphocytes of syphilitic rabbits was studied. Treponema pallidum-killing activity of ATL was slightly reduced after heating at 56 degrees C and completely abolished at 100 degrees C. The significant reduction of the activity was also obtained after exposure of ATL to acidic conditions (pH 1-5) at room temperature, or by treatment with papain and neuraminidase. Activity of ATL was completely resistant to deoxyribonuclease, ribonuclease and trypsin treatment. ATL was eluted from the Sephadex G-100 column together with hemoglobin, that suggested the apparent molecular weight of ATL of about 65,000. The active fraction from the Sephadex G-100 column was further fractionated on DEAE-Sephadex A-50. The activity of ATL was widely spread in the column eluate, indicating the charge heterogeneity. All these data indicate that ATL is a relatively low molecular weight protein. The sensitivity to neuraminidase and heterogeneity of charge suggest that it is a glycosylated protein.

Animals↗

Anti-ATLA (antibody to adult T-cell leukemia-lymphoma virus-associated antigen)-negative adult T-cell leukemia-lymphoma.

Five cases of adult T-cell leukemia-lymphoma (ATL) having typical clinicohematologic and morphologic features but negative for anti-ATLA [antibody to ATL virus (ATLV)-associated antigen (ATLA)] are presented. Some differences in immunologic, epidemiologic, and serologic data between anti-ATLA-positive and -negative ATLs are also described. Expression of ATLA in early primary cultured leukemic cells was found to be negative in three patients tested (Cases 1, 2 and 4), however, a long-term cultured cell line, ATL-6A, derived from peripheral blood leukemia cells from Case 1, was found to express ATLA. Mother of Case 1 and a daughter of Case 2 were anti-ATLA negative. These results indicate that ATLV was involved in certain anti-ATLA-negative ATL patients, at least in Case 1, and that the patient had no detectable immune response against ATLV and ATLA. However, in other cases in which no ATLA reactivity of serum and no ATLA expression in cultured leukemic cells were observed, another possibility such as activation of an unknown cellular oncogene specific for ATL without ATLV involvement may be considered. In order to prove these possibilities definitely, it is necessary to elucidate whether or not proviral DNA of ATLV is integrated into chromosomal DNA of ATL cells and to find a cellular oncogene specific for ATL in the future.

Adult↗

Incidence of antibody to adult T-cell leukemia-virus-associated antigen among T-cell malignancies in the Kyoto District, with a report of two unusual cases.

Titration of antibody to adult T-cell leukemia (ATL)-virus-associated antigen (ATLA) is of much help for diagnosing ATL, because almost all patients with ATL are seropositive even in an ATL-nonendemic area such as Kyoto. In T-cell lymphoma, anti-ATLA antibody was thought to be related to the birthplace of the patients and the epidermotropism of their skin lesions, but it was not confirmative because the number of cases was so small. We present here two curious cases of anti-ATLA-negative T-cell leukemia/lymphoma. A 53-yr-old man, born in a nonendemic area, had manifestations similar to those of ATL except for the lack of skin involvement, but the morphology of his leukemic cells was less like that of ATL cells than that of prolymphocytic leukemia cells. Therefore, his leukemia was not diagnosed as ATL. A 52-yr-old woman, whose parents' hometown was in an endemic area, showed typical manifestations of nonleukemic T-cell lymphoma, and her biopsied lymph node was compatible with diffuse, pleomorphic lymphoma histologically. In the latter patient, the negative anti-ATLA finding might be due to titration sensitivity. Therefore, the clinical and hematologic features are still informative for distinguishing ATL from other T-cell malignancies.

Antibodies, Viral↗

Constitutive overexpression of the L-selectin gene in fresh leukemic cells of adult T-cell leukemia that can be transactivated by human T-cell lymphotropic virus type 1 Tax.

L-selectin is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium. Upon cellular activation, expression of the L-selectin gene is downregulated at both the protein and mRNA levels. To understand the mechanism of leukemic cell infiltration into organs, we studied the expression and regulation of L-selectin mRNA in fresh leukemic cells of adult T-cell leukemia (ATL) patients and investigated the response of the L-selectin promoter to human T-cell lymphotropic virus type 1 (HTLV-1) Tax, which is a viral transcriptional transactivator. Flow cytometry showed that L-selectin was expressed on fresh ATL cells along with other activation antigens. Northern blot analysis showed that ATL cells overexpressed that L-selectin mRNA and that the level was aberrantly upregulated after PMA stimulation. Studies using in situ hybridization showed expression of the L-selectin mRNA in the infiltrating leukemic cells in the liver of two ATL patients. Intravenous injection of a rat T-cell line that overexpresses L-selectin showed increased organ infiltration. The induction of Tax expression in JPX9 cells resulted in about a twofold increase in the mRNA expression levels compared with the basal level. Chloramphenicol acetyltransferase (CAT) assay after transient cotransfection showed about a fivefold transactivation of the L-selectin promoter by Tax. The serum level of the shed form of L-selectin was significantly increased in ATL patients (mean +/- SD, 4,215.4 +/- 4,111 ng/mL) compared with those of asymptomatic carriers and healthy blood donors (mean +/- SD, 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL, respectively). These results indicated that ATL cells constitutively overexpress the L-selectin gene that can be transactivated by HTLV-1 Tax. The overexpression of L-selectin, as well as of inflammatory cytokines, by ATL cells may provide a basis for ATL cells to attach the vascular endothelium, leading to transmigration and organ infitration.

Adult↗

E-selectin and vascular cell adhesion molecule-1 mediate adult T-cell leukemia cell adhesion to endothelial cells.

We studied the adhesion properties of peripheral blood leukemic cells from 10 patients with adult T-cell leukemia (ATL) to endothelial cells to better understand the mechanism of leukemic cell infiltration. ATL cells expressed lymphocyte function-associated antigen-1 (LFA-1), but the expression of very late antigen-4 (VLA-4) and sialyl-Lewisx (SLex) was variable. They did not express sialyl-Lewisa (SLea). Cell adhesion assays, which were performed in nine patients, showed marked adhesion of ATL cells to interleukin [IL]-1-activated human umbilical vein endothelial cells (HUVEC). A monoclonal antibody (MoAb) against E-selectin consistently inhibited ATL cell adhesion, and an MoAb against vascular cell adhesion molecule-1 (VCAM-1) or an MoAb against VLA-4 sometimes diminished it. In contrast, an MoAb against LFA-1 had a minor effect on freshly isolated ATL cell adhesion to HUVEC. The percentage of SLex+ cells in the cell population adherent to IL-1-activated HUVEC was slightly higher than that in unseparated cells. These results, together with the detection of E-selectin expression on the endothelium at ATL skin lesions, indicate that E-selectin-mediated adhesion is the major pathway for the adherence of ATL cells to endothelial cells. In addition, the ligand for E-selectin on ATL cells appears to differ from that on neutrophils.

Antibodies, Monoclonal↗

[Problems concerned with adult T-cell leukemia. 1) Causes of death and early diagnosis of cytomegalovirus pneumonia in adult T-cell leukemia. 2) Clinicopathological features of CD30 positive adult T-cell leukemia].

1) We studied the causes of death confirmed by autopsy or necropsy in 23 adult T-cell leukemia (ATL) patients. Of them eight showed involvement of tumor (35%), eleven infectious disease (47%) (nine cytomegalovirus (CMV) pneumonia, one varicella-zostervirus pneumonia, one pseudomonas aeruginosa pneumonia), and four others (17%). In seven recent cases treated with a new chemotherapy regimen in combination with G-CSF administration, survival was longer than in previous cases and tumor involvement as a cause of death decreased (one case, 14%). However, CMV pneumonia inclined to increase (six cases, 86%). Therefore, we tried to retrospectively detect CMV DNA in the serum of ATL patients using a nested polymerase chain reaction (PCR). CMV pneumonia was reliably diagnosed in eleven ATL patients, whereas CMV DNA was detected in all patients at the time of clinical onset of pneumonia and CMV DNA was detected only in eight patients from 7-35 days before the onset of pneumonia. These findings suggest that the nested PCR assay is a useful tool to early diagnosis CMV pneumonia in ATL patients. 2) Recently, several cases of ATL with CD30 antigen have been reported, but its clinical relevance remains unknown. Accordingly, we studied CD30 antigen expression in 36 ATL patients who had monoclonal integration of HTLV-I provirus in the tumor cells and demonstrated the immunohistochemical and clinical characteristics of these patients. CD30 antigen expression was evident in seven of these 36 patients (19.4%). A comparison of ATL cases with and without CD30 antigen expression revealed significantly large numbers of abnormal lymphocytes in the peripheral blood and lower serum calcium levels in CD30 antigen positive ATL.

Adult↗

Abnormal cytokine expression in Sézary and adult T-cell leukemia cells correlates with the functional diversity between these T-cell malignancies.

The Sézary syndrome (SzS) and adult T-cell leukemia (ATL) are malignant proliferations of mature T-lymphocytes that possess distinct functions. Sézary cells function as helper cells, whereas ATL cells are usually suppressor effectors. Although phenotypically similar (CD4+/CD7-/CD8-), these functional differences between the T-cell lymphoproliferative disorders suggest different patterns of cytokine expression. We wished to delineate the cytokine mechanisms potentially underlying the diverse functional characteristics of SzS and ATL. Therefore, we analyzed the expression of interleukins (IL) 2, 4, and 5, gamma-interferon, and transforming growth factor beta 1 in the highly purified leukemic T-cells from 5 SzS and 5 ATL patients. Decreased mRNA and protein levels of IL-2, gamma-interferon, and IL-5 were detected in mitogen-stimulated ATL and SzS cells when compared to similarly cultured normal CD4+ cells. In contrast, IL-4 production was markedly up-regulated in the leukemic cells of 4/5 SzS patients as compared to ATL and normal controls. Finally, fresh ATL cells secreted higher levels of transforming growth factor beta 1 into the culture medium than the malignant T-cells from SzS patients. Collectively these results suggest that, similar to the murine CD4-expressing T-cell subsets Th1 and Th2, different cytokine profiles exist in a human population of CD4+ T-cells. Moreover, the distinct patterns of IL-4 and transforming growth factor beta 1 expression by SzS and ATL cells, respectively, are most consistent with the functional differences (i.e., helper versus suppressor activity) between these T-cell malignancies and thus may play important roles in the pathogenesis of the paraneoplastic features associated with these two leukemias.

Adult↗

A new classification of clinical stages of adult T-cell leukemia based on prognosis of the disease.

Adult T-cell leukemia (ATL) has been classified into three clinical subtypes: acute, chronic, and smoldering type. However, these clinical subtypes of ATL do not always correlate with prognosis. We propose a new criterion for classification of clinical stages of ATL, based on the expression of Ki-67 antigen in peripheral blood T lymphocytes. We analyzed Ki-67 antigen expression in 45 ATL patients, classified as 18 acute, 17 chronic, and ten smoldering type. We found that in 23 patients with more than 18% Ki-67 antigen-positive T cells, the disease progressed very aggressively, and all patients died within 1 year (mean survival, 105 days). This group included 15 of 16 patients classified as 'acute', seven of 15 patients classified as 'chronic', and one of nine patients classified as 'smoldering' type. In contrast, 15 out of 17 patients with less than 18% Ki-67 antigen-positive T cells were still alive at the end of the study, with a mean survival of 750 days. Only two patients died in this group, and after a very long survival (599 and 978 days, respectively). We therefore propose the following new classification for ATL: (i) Aggressive ATL; percentage of Ki-67 antigen-positive cells more than 18% in peripheral blood T lymphocytes, (ii) Stable ATL; percentage less than 18%. This classification strongly correlates with the prognosis of patients with ATL.

Acute Disease↗

Comparative study of cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma.

An important disease entity distinct from cutaneous T-cell lymphoma (CTCL) in Japan is adult T-cell leukemia/lymphoma (ATL), which shows almost the same phenotype as CTCL, ie, a helper/inducer T-cell phenotype (CD4-positive, CD8-negative), and usually involves the skin. This article describes differences between CTCL and ATL in terms of clinical and immunopathologic cell surface features. In patients with ATL, the predominant physical findings were lymph node, bone marrow and skin involvement, hepatosplenomegaly, leukemic manifestations, and an aggressive course. In patients with CTCL, in contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was shown. The predominant phenotype of the neoplastic cells in the skin of patients with CTCL was CD3+, CD4+, CD29+, CD45RO+, HLA-DR+, HLA-DQ+, CD7-, L-selectin-, and CD45RA-. Some phenotypic discrepancy was found between the neoplastic cells in the peripheral blood, lymph nodes and skin of patients with ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25, and HLA-DR. That is, the predominant neoplastic cell phenotype was helper T-cell, which was CD3+, CD4+, L-selectin+, CD25+, CD45RA+, HLA-DR+, CD29-, and CD45RO- in peripheral blood, and CD3+, CD4+, L-selectin+, CD29+, CD45RO+, HLA-DR+, and CD45RA- in the skin and lymph nodes. Phenotypic heterogeneity of ATL cells and heterogeneity of CD45R isoform expression on ATL cells were evident in different organs. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL. CTCL cells do not share the same phenotype as ATL cells.

Adult↗

An enhanced surveillance program for adult T-cell leukemia in central Brooklyn.

The Brooklyn Adult T-cell Leukemia/Lymphoma (ATL) study was developed to estimate the incidence of the human T-cell lymphotropic virus type I (HTLV-I)-associated ATL in the Crown Heights/Bedford Stuyvesant community. This central Brooklyn black community is an area which has already been shown in earlier reports to be endemic for HTLV-I-associated ATL. Surveillance has been conducted at seven area hospitals that serve this community, with surveillance already completed at five hospitals. Potential study subjects who are 20 years or older are identified by the review of admission records, discharge summaries, pathology and clinical chemistry reports, or physician referrals. Diagnoses of leukemia or lymphoma, or the presence of leukocytosis or hypercalcemia are used as criteria to identify the subjects. Participating subjects give a sample of blood for the determination of HTLV-I infection by serologic tests. At the time of enrollment, subjects provide demographic information including age, sex and birthplace. After one year of surveillance at five hospitals (39.5% of inpatient beds in the catchment), we have identified 12 cases of HTLV-I-associated ATL. The mean age of the ATL patients was 50 years, with patients being predominantly female (83.3%) and often Caribbean immigrants (83.3%). Interestingly, 42% of our cases were identified solely by findings of hypercalcemia from clinical chemistry reports. The remaining ATL cases were identified by physician referral. This enhanced surveillance program that uses both clinical and laboratory criteria for ATL case ascertainment can serve as a prototype for similar surveillance in other areas endemic for HTLV-I-associated ATL--an important effort because of the strong potential for disease prevention.

Adult↗

Two types of defective human T-lymphotropic virus type I provirus in adult T-cell leukemia.

Adult T-cell leukemia (ATL), an aggressive neoplasm of mature helper T cells, is etiologically linked with human T lymphotropic virus type I (HTLV-1). After infection, HTLV-I randomly integrates its provirus into chromosomal DNA. Since ATL is the clonal proliferation of HTLV-I-infected T lymphocytes, molecular methods facilitate the detection of clonal integration of HTLV-I provirus in ATL cells. Using Southern blot analyses and long polymerase chain reaction (PCR) we examined HTLV-I provirus in 72 cases of ATL, of various clinical subtypes. Southern blot analyses revealed that ATL cells in 18 cases had only one long terminal repeat (LTR). Long PCR with LTR primers showed bands shorter than for the complete virus (7.7 kb) or no bands in ATL cells with defective virus. Thus, defective virus was evident in 40 of 72 cases (56%). Two types of defective virus were identified: the first type (type 1) defective virus retained both LTRs and lacked internal sequences, which were mainly the 5' region of provirus, such as gag and pol. Type 1 defective virus was found in 43% of all defective viruses. The second form (type 2) of defective virus had only one LTR, and 5'-LTR was preferentially deleted. This type of defective virus was more frequently detected in cases of acute and lymphoma-type ATL (21/54 cases) than in the chronic type (1/18 cases). The high frequency of this defective virus in the aggressive form of ATL suggests that it may be caused by the genetic instability of HTLV-I provirus, and cells with this defective virus are selected because they escape from immune surveillance systems.

Adult↗

Distinct phenotype of leukemic T cells with various tissue tropisms.

There is an emerging concept, the validity of which remains to be proven, that preferential expression of selective adhesion molecules on particular T cell subsets may result in tissue-specific migration. L-selectin, cutaneous lymphocyte-associated Ag (CLA), and integrin alpha4beta7 are proposed to be involved in selective migration of T cell subsets into peripheral lymph nodes, skin, and gastrointestinal mucosa, respectively. Adult T cell leukemia (ATL) is associated with lymphoid infiltration of tissues and secondary lymphoid organs. To clarify the role of these putative homing molecules in vivo, we assessed their expression on circulating ATL cells from patients with lymph node, skin, and gut involvement. L-selectin expression was significantly higher on peripheral ATL cells in patients with lymphadenopathy than in patients without it. CLA was highly expressed on peripheral ATL cells compared with normal T cells: its expression was also significantly higher on peripheral ATL cells from patients with skin involvement compared with cells from patients without it. beta7 was particularly highly expressed on peripheral ATL cells from patients with gastrointestinal involvement. In summary, the differential expression of beta7 and beta1 on peripheral ATL cells correlates with the presence of gastrointestinal involvement. Similarly, the presence of skin involvement is associated with the expression of CLA(high)beta7low on peripheral ATL cells. These results, which are consistent with the molecules CLA and alpha4beta7 mediating preferential T cell migration to the skin and gastrointestinal mucosa, respectively, may allow for a refinement of the classification of lymphoid neoplasms on the basis of differential expression of homing molecules.

Adult↗

Analysis of surgical participation in the Advanced Trauma Life Support course. What are the goals and are we meeting them?

Advanced Trauma Life Support (ATLS) course records spanning 4 years were examined and American College of Surgeons members in Washington State surveyed to gain further information on ATLS course participants, skills utilization, and hospital credentialing. Thirty-seven (9.7%) of 382 course participants were trained general surgeons, 56 (14.7%) were surgical residents, and 12 (3.1%) were surgical specialists. One hundred thirty-six (35.6%) of the participants were primary care physicians and 115 (30.1%) were emergency physicians. Surgical residents, primary care physicians, and emergency physicians tended to be overrepresented in ATLS courses in comparison with their general distribution. Fully trained surgeons and surgical specialists were underrepresented. Course participants represented 3.8% of all physicians involved in patient care in the state. Only 6.4% of all active general surgeons in the state were participants, while 39% of active emergency physicians participated. The successful completion rate was 94% (98% for surgeons and 92% for nonsurgical physicians). Thirty-one percent of all American College of Surgeons survey respondents (31% of urban practitioners and 21% of rural practitioners) reported current ATLS qualification. Advanced Trauma Life Support qualification was reported by 31% of respondents as a requirement for taking trauma/emergency department call. Surgeons with a preference not to treat patients with trauma were less likely to have ATLS qualification. More than half of those who reported ATLS qualification had not performed a tracheal intubation, cricothyroidotomy, pericardiocentesis, or emergency department thoracotomy in the previous year. Participation of surgeons in ATLS courses is low, particularly among rural practitioners. Impetus for participation appears related to requirements for hospital staff credentialing and preferences for treating patients with trauma. Performance of procedures taught in the course is rare. Strategies to increase participation need to be formulated and implemented.

Education, Medical, Continuing↗

High occurrence of primary malignant neoplasms in patients with adult T-cell leukemia/lymphoma, their siblings, and their mothers.

BACKGROUND: Attempts were made to clarify the correlation between human T-cell leukemia/lymphoma virus (HTLV)-1 infection and malignant oncogenicity other than adult T-cell leukemia/lymphoma (ATL) in a case-control study. METHODS: The occurrence of primary malignant neoplasms (MN) in 110 ATL patients, their parents, and 430 siblings was compared with HTLV-1 seronegative non-Hodgkin's lymphoma (NHL) patients, their parents and 867 siblings. The chi-square test, odds ratio (OR), and 95% confidence intervals (CI) were used to determine the statistical significance of differences in the occurrence of the primary MN among ATL patients, HTLV-1 seronegative NHL patients, their siblings, and their parents. RESULTS: The occurrence of primary MN in the ATL patients was higher than the occurrence in HTLV-1 seronegative NHL patients (P = 0.0036; OR = 2.91; 95% CI: 1.42, 6.02). In siblings of the ATL patients, there was a higher occurrence of primary MN than in siblings of the HTLV-1 seronegative NHL patients (P < 0.0001; OR = 3.35; 95% CI: 2.01, 5.58). In mothers of the ATL patients, there was a higher occurrence of primary MN than in mothers of the HTLV-1 seronegative NHL patients (P = 0.0063; OR = 2.55; 95% CI: 1.30, 5.00), but not in fathers (P = 0.1602; OR = 1.68; 95% CI: 0.81, 3.47). CONCLUSIONS: There is an increased risk of primary MN in ATL patients, their siblings, and their mothers.

Aged↗