Teruo Ino

Medical student abuse during clinical clerkships in Japan

AbstractOBJECTIVE: To assess the prevalence of medical student abuse during clinical clerkships in Japan. DESIGN: A cross-sectional questionnaire survey. SETTING: Six medical schools in Japan. PARTICIPANTS: Final year (sixth-year) and fifth-year medical students in the period from September 2003 to January 2004. From a total of 559 students solicited, 304 (54.4%) returned the questionnaire, and 276 (49.4%: 178 male and 98 female) completed it. MEASUREMENTS: Prevalence of medical student abuse in 5 categories: verbal abuse, physical abuse, academic abuse, sexual harassment, and gender discrimination; differences in abusive experience between male and female students; types of alleged abusers; reporting abusive experiences to authorities; and emotional effects of abusive experiences. RESULTS: Medical student abuse was reported by 68.5% of the respondents. Verbal abuse was the most frequently experienced abuse (male students 52.8%, female students 63.3%). Sexual harassment was experienced significantly more often (P<.001) by female students (54.1%) than by male students (14.6%). Faculty members were most often reported as abusers (45.2% of cases). Abuse occurred most frequently during surgical rotations (42.0% of cases), followed by internal medicine (25.1%) and anesthesia rotations (21.8%). Very few abused students reported their abusive experiences to authorities (8.5%). The most frequent emotional response to abuse was anger (27.1% of cases). CONCLUSIONS: Although experience of abuse during clinical clerkships is common among medical students in Japan, the concept of “medical student abuse” is not yet familiar to Japanese. To improve the learning environment, medical educators need to take action to resolve this serious issue.

Acute leukemia with the phenotype of a natural killer/T cell bipotential precursor

Abstract An acute leukemia with an unusual immunophenotype developed in a 17-year-old girl. At the initial presentation, extramedullary involvement was not evident, but with advancing disease, massive splenomegaly and an osteolytic rib tumor developed. The disease was aggressive and refractory to intensive chemotherapeutic regimens for myeloid and lymphoid malignancies, and the patient died 3 months after the initial presentation. The leukemic cells were of irregular shape and variable size; they had deeply indented or bi-lobed nuclei and relatively fine, azurophilic granules in their cytoplasm. They were positive for acid phosphatase and β-glucuronidase in granular staining, but they were negative for myeloperoxidase. The leukemic cells had a unique immunophenotype: it was positive for T-cell antigens (CD1a, CD2, cytoplasmic CD3, CD4), myeloid antigens (CD13 and CD33), NK-cell antigen (CD56), CD19 and CD30. DNA analysis revealed no gene rearrangement in the T-cell receptor β, γ and δ, or immunoglobulin heavy chain genes. The leukemic cells of our patient are thought to have arisen from the transformation of a putative precursor cell common to both the T- and NK-cell lineage in the bone marrow. The current literature on precursor NK-cell malignancy is reviewed, and its clinicopathological feature is discussed.

Translocation (3;21)(q26;q22) in treatment-related acute leukemia secondary to acute promyelocytic leukemia

We performed cytogenetic studies in a patient with treatment-related acute leukemia (t-AL) to identify the associated chromosomal changes. Metaphase analysis revealed a t(3;21)(q26;q22) translocation. Acute promyelocytic leukemia (APL) had been diagnosed 4 years earlier and the patient had received intensive induction chemotherapy and sequential post-induction therapy that included agents that targeted DNA-topoisomerase II (topo II). This case suggests an association between previous therapy with topo II inhibitors and development of t-AL associated with a balanced aberration involving the 3q26 and 21q22 bands.

Proliferative effects of several hematopoietic growth factors on acute myelogenous leukemia cells and correlation with treatment outcome

The response of human acute myelogenous leukemia (AML) cells to four different hematopoietic growth factors (granulocyte–macrophage colony-stimulating factor (GM-CSF), interleukin-1 β (IL-1β), interleukin-3 (IL-3), and stem cell factor (SCF)) and the relationship of the proliferative response of the AML cells to treatment outcome were studied. Proliferative responses were analyzed in 79 patients with de novo AML and 19 patients with AML arising from myelodysplastic syndrome (MDS). In de novo AML, a positive proliferative response (stimulation index >2) was seen in 65 to 75% of cases. AML cells arising from MDS had a much higher incidence of proliferative response to each growth factor (79 to 90%) and a much higher level of 3H-TdR incorporation. The relationship to treatment outcome was evaluated in 79 patients with de novo AML. The patients whose leukemic cells had a positive proliferative response to any growth factor, especially IL-3 and SCF, had a poorer outcome, ie a lower complete remission (CR) rate, shorter CR duration, and shorter survival. The outcome was particularly poor in patients whose leukemic cells had proliferative responses to all four or any of the growth factors, compared to patients whose leukemic cells had no response. This increased response may be a marker of poor prognosis in patients with AML.

Alternating non‐cross‐resistant chemotherapy for non‐Hodgkin's lymphoma of intermediate‐grade and high‐grade malignancy. A pilot study

Thirty‐two patients with advanced non‐Hodgkins lymphoma (NHL) with aggressive histologic findings were treated with cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide, and prednisolone (CAMBO‐VIP), in which presumably non‐cross‐resistant myelosuppressive and nonmyelosuppressive agents were administered during alternate weeks for 12 weeks. To ensure the high‐dose intensity of the protocol, dose reduction and delay in treatment were minimized. Three patients were treated inadequately. Twenty‐six (89.7%) of 29 evaluable patients had a complete response, and three had a good partial response. Relapse occurred in four patients, with a median follow‐up of 29 months. The actuarial overall survival and disease‐free survival were estimated to be 87.6% and 75.9%, respectively. The CAMBO‐VIP treatment was well tolerated; myelosuppression was severe but transient and caused no serious infections. Side effects that affected dose intensity were oral ulceration, occurring in 28 patients, and blister formation under the thickened skin of palms and/or soles, followed by desquamation (5 patients). Hepatic toxicity was generally mild to moderate; it was severe in one patient. A 12‐week regimen of CAMBO‐VIP was effective for advanced NHL with aggressive histologic findings.

Quality of care associated with number of cases seen and self-reports of clinical competence for Japanese physicians-in-training in internal medicine

BackgroundThe extent of clinical exposure needed to ensure quality care has not been well determined during internal medicine training. We aimed to determine the association between clinical exposure (number of cases seen), self- reports of clinical competence, and type of institution (predictor variables) and quality of care (outcome variable) as measured by clinical vignettes.MethodsCross-sectional study using univariate and multivariate linear analyses in 11 teaching hospitals in Japan. Participants were physicians-in-training in internal medicine departments. Main outcome measure was standardized t-scores (quality of care) derived from responses to five clinical vignettes.ResultsOf the 375 eligible participants, 263 (70.1%) completed the vignettes. Most were in their first (57.8%) and second year (28.5%) of training; on average, the participants were 1.8 years (range = 1–8) after graduation. Two thirds of the participants (68.8%) worked in university-affiliated teaching hospitals. The median number of cases seen was 210 (range = 10–11400). Greater exposure to cases (p = 0.0005), higher self-reports of clinical competence (p = 0.0095), and type of institution (p < 0.0001) were significantly associated with higher quality of care, using a multivariate linear model and adjusting for the remaining factors. Quality of care rapidly increased for the first 100 to 200 cases seen and tapered thereafter.ConclusionThe amount of clinical exposure and levels of self-reports of clinical competence, not years after graduation, were positively associated with quality of care, adjusting for the remaining factors. The learning curve tapered after about 200 cases.

Interleukin-1β (IL-1β) and acute leukemia: In vitro proliferative response to IL-1β, IL-1β content of leukemic cells and treatment outcome

We evaluated the in vitro proliferative response to exogenous IL-1β in terms of tritiated thymidine (3H-TdR) incorporation in leukemic cells obtained from 119 patients with various types of acute leukemia. The content of IL-1β in leukemic cells was measured by enzyme-amplified sensitivity immunoassay. We observed a significant proliferative response to exogenous IL-1β in leukemic cells from 2766 patients with de novo AML, 129 patients with ALL, 23 patients with AUL, 812 patients with AML arising from MDS, 47 patients with myeloid crisis of CML, and 04 patients with lymphoid crisis of CML. Proliferation was marked in myeloid leukemic cells of a more premature stem cell origin. There were no significant differences in proliferative responses among the different FAB classes of de novo AML. The IL-1β content of leukemic cells was low in patients with lymphoid leukemia, but there was no significant difference among the various types of myeloid leukemia. There was no correlation between the proliferative response to exogenous IL-1β and the IL-1β content of leukemic cells. When we correlated the proliferative response to exogenous IL-1β with treatment outcome in patients with de novo AML, we found the rate of complete remission (CR) to be lower in those with a high proliferative response. We noted a longer duration of CR (p = 0.07) and of survival (p < 0.05) in patients with a low proliferative response. Thus, a high proliferative response to IL-1β in the cells of AML patients may indicate a poor prognosis.

Intensive sequential post-induction therapy for adults with acute myelogenous leukemia in first remission: Long-term follow-up and results

We designed a post-induction therapy including intensive sequential therapy with non-cross-resistant drugs in an effort to prolong disease-free survival (DFS) for adults with acute myelogenous leukemia. Forty-five patients entered this study and 33 of 35 patients entering complete remission received the post-induction therapy. With a median follow-up for survivors of 3.5 years from complete remission, the actuarial 5-year DFS was 46% +/- 19% (95% confidence interval). The five-year DFS for patients over 45 years of age was comparable to that for patients under 45 years of age (50% +/- 26% vs 47% +/- 28%). Furthermore, the actuarial 5-year DFS for patients who required two courses of induction therapy was comparable to that for patients who required only one course of induction therapy (45% +/- 29% vs 50% +/- 25%). The toxicity of post-induction therapy was tolerable and no patients died during complete remission.

Increased dosage of donepezil for the management of behavioural and psychological symptoms of dementia in dementia with Lewy bodies.

As with other types of dementia, the behavioral and psychological symptoms of dementia (BPSD) can make caregiving difficult for patients with dementia with Lewy bodies (DLB). We hypothesized that administration of donepezil at an increased dose of 10 mg/day might dose‐dependently improve BPSD in DLB patients with relapse, after their symptoms had been controlled initially by donepezil therapy at the standard dose.

Lysis of autologous tumor cells by large granular lymphocytes in patients with acute leukemia in complete remission: Correlation between lytic activity and clinical outcome

In order to evaluate the effect of specific immune response on prognosis in acute leukemia, we investigated the correlation between the lysis of autologous tumor cells (ATC) by lymphocytes and prognosis. Peripheral mononuclear cells (PMC) from most patients with acute leukemia in complete remission (CR) do not exhibit cytotoxic activity against fresh-frozen ATC, although they have adequate cytotoxic activity against K562 cells. When the large granular lymphocyte (LGL) fraction was used in this study, we observed lysis of ATC in 17 (43.6%) of 39 patients with acute leukemia (12 (42.9%) of the 28 patients with acute myelogenous leukemia (AML) and 5 (45.5%) of the 11 patients with acute lymphocytic leukemia (ALL)). With regard to prognosis, the lytic activity of the LGL fraction did not reflect the duration of CR. The median CR duration in AML patients was 13 months for the lysis-positive group and 11 months for the lysis-negative group. No significant correlation was also found between lytic activity of the LGL fraction and overall survival in each patient. However, the lysis-positive group tended to have a longer survival, the median overall survival being 48 months for the lysis-positive group vs 12 months for the lysis-negative group. The prolonging of overall survival in the lysis-positive group was attributed to a high rate of induction of second remissions in this group. Long-term patient survival in the two groups did not differ.