[Evaluation of the efficacy of GnRH-a pretreatment before total hysterectomy for adenomyosis patients: a propensity score matching analysis].

Objective: To evaluate the efficacy of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment before total hysterectomy for adenomyosis patients with uterine volume ≥12 gestational weeks and moderate or severe anemia. Methods: From January 2018 to March 2023, 689 patients who underwent total hysterectomy for adenomyosis in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. According to the preoperative medication, they were divided into study group (127 cases) and control group (562 cases). Patients in the study group underwent GnRH-a pretreatment for 3 cycles before surgery, and the control group received operation directly. SPSS 26.0 software was used to perform 1∶1 matching for the two groups of patients through the propensity score matching method. Matching variables included age, body mass index, gravidity, parity, history of pelvic and abdominal surgery, menstrual cycle, menstrual period, dysmenorrhea score, initial diagnosis of cancer antigen 125 (CA125), uterine volume and hemoglobin value. The dysmenorrhea score, uterine volume, hemoglobin value and CA125 level before and after GnRH-a pretreatment in the study group were compared. And the duration of operation, intraoperative blood loss, postoperative white blood cell count, perioperative blood transfusion cases, postoperative disease rate, duration of hospitalization, total hospitalization cost between the two groups were compared. Results: With propensity score matching, 119 patients in the study group and 119 patients in the control group were finally enrolled in this study. In the study group, before and after the treatment with GnRH-a, the dysmenorrhea score (7.4±1.7 vs 5.6±1.8), uterine volume [(362±160) vs (233±126) cm3], hemoglobin value [(74.1±10.7) vs (102.5±13.5) g/L], and CA125 level [(104±76) vs (64±51) kU/L] were statistically different (all P<0.05). There were statistical differences of operation time [(86±18) vs (116±31) minutes], intraoperative blood loss [(24±9) vs (43±22) ml], white blood cell count after 1 day of operation [(9.80±0.10)×109/L vs (9.90±0.10)×109/L], number of perioperative blood transfusion case [5.9% (7/119) vs 61.3% (73/119)], postoperative disease rate [5.0% (6/119) vs 16.0% (19/119)], hospitalization duration [(7.1±1.6) vs (7.9±1.6) days], and total hospitalization cost [(35 323±5 275) vs (37 159±5 640) yuan] between the study group and the control group (all P<0.05). Conclusion: The pretreatment of using GnRH-a before total hysterectomy for adenomyosis patients with uterine volume ≥12 gestational weeks and moderate or severe anemia is not only conducive to improving dysmenorrhea, signs of anemia, reducing uterine volume, but also conducive to the implementation of surgery, reducing intraoperative and postoperative complications, and reducing hospital costs.

[The effect of microRNA-21 on myocardial fibrosis in mice with chronic viral myocarditis].

Objective: To explore the effect of microRNA-21 (miR-21) on myocardial fibrosis in mice with chronic viral myocarditis (CVMC) and related mechanisms. Methods: Forty 4-week-old Balb/c male mice were randomly divided into 4 groups (n=10 each): phosphate buffer saline (PBS) group, CVMC group, CVMC+miR-21 inhibitor group, CVMC+isotype control group. The first injection of Coxsackie virus B3 (CVB3) or PBS was performed on day 0, and the total study time was 42 days. Each mouse in CVMC group, CVMC+miR-21 inhibitor group and CVMC+isotype control group was intraperitoneally (i.p) injected with 100TCID50 CVB3 0.1, 0.15, and 0.2 ml on day 0, 14, and 28, respectively. The mice in PBS group were i.p injected with the same dose of PBS at the same time point. After the initial infection, each mouse in CVMC+miR-21 inhibitor group and CVMC+isotype control group was intravenously injected with 0.1 ml miR-21 inhibitor or 0.1 ml isotype control, on day 14 and 28. Cardiac function was measured on surviving mice of 4 groups by echocardiography on day 42. Then, the hearts were removed aseptically to observe the expressions of green fluorescence protein (GFP). The myocardial pathological changes were examined with HE, Masson staining and the myocardial pathological scores (PS), the collagen volume fraction (CVF) were calculated respectively. The levels of miR-21, collagen typeⅠ-A1 (COL1-A1) and collagen type Ⅲ-A1 (COL3-A1) mRNA in heart were detected by quantitative real-time polymerase chain reaction (RT-qPCR). Furthermore, the expressions of transforming growth factor-ß1 (TGF-ß1) and mothers against decapentaplegic homolog 7(Smad7) in heart were determined with Western blot assay. Results: (1) Cardiac function in 4 groups: Compared with PBS group, left ventricular end systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD) were markedly increased in CVMC group and CVMC+isotype control group (all P<0.05), whereas the left ventricular ejection fraction (LVEF) was decreased (P<0.05). LVESD and LVEDD were significantly decreased, and LVEF was increased in CVMC+miR-21 inhibitor group compared with those in CVMC group and CVMC+isotype control group (all P<0.05). (2) Myocardial pathological changes: The expressions of GFP in CVMC+miR-21 inhibitor group and CVMC+isotype control group were visible in heart tissues frozen sections. The hearts in CVMC group and CVMC+isotype control group were enlarged and stiff, inflammatory cells were visible and significantly increased myocardial fibrosis was evidenced in mice of these two groups. Higher PS and CVF were evidenced in CVMC group (PS: 1.14±0.69 vs. 0, CVF: (17.86±2.61)% vs. (5.70±1.42)%, all P<0.05) and CVMC+isotype control group(PS: 1.00±0.63 vs. 0, CVF: (16.78±2.58)% vs. (5.70±1.42)%, all P<0.05) compared to PBS group. Compared with CVMC group and CVMC+isotype control group, degree of cardiac fibrosis was reduced in mice of CVMC+miR-21 inhibitor group (CVF: (11.01±2.55)% vs. (17.86±2.61)%, (11.01±2.55)% vs. (16.78±2.58)%, all P<0.05), whereas PS were similar between them (PS: 0.89±0.60 vs. 1.14±0.69, 0.89±0.60 vs. 1.00±0.63, all P>0.05). (3) Cardiac expressions of miR-21, COL1-A1 and COL3-A1 mRNA: The cardiac expressions of miR-21, COL1-A1 mRNA, COL3-A1mRNA in CVMC group and CVMC+isotype control group were markedly higher than those in PBS group (all P<0.05), which were significantly downregulated in CVMC+miR-21 inhibitor group (all P<0.05 vs. CVMC group and CVMC+isotype control group). (4) The cardiac expressions of TGF-ß1 and Smad7 protein: The cardiac expressions of TGF-ß1 protein in CVMC group and CVMC+isotype control group were markedly higher, whereas the cardiac Smad7 protein expressions were significantly lower (all P<0.05) than those in PBS group (all P<0.05), these changes could be reversed in CVMC+miR-21 inhibitor group (P<0.05 vs. CVMC group and CVMC+isotype control group). Conclusions: Our results suggest that miR-21 contributes to the myocardial fibrosis in CVMC mice through modulating TGF-ß1/Smad7 signaling pathway.

Effect of cigarette taxes on the consumption of cigarettes, alcohol, tea and coffee in Taiwan.

OBJECTIVES: To analyse whether a health tax of 10 New Taiwan Dollars (NT$) (US$0.3) imposed on cigarettes in 2009 will help to reduce cigarette consumption, and whether or not the cigarette tax will affect consumption of alcohol, coffee and tea. STUDY DESIGN: Time series data for consumption and retail prices of tobacco, alcohol, tea and coffee were collected and analysed for the period 1973-2007. METHODS: To establish the Central Bureau of Statistics demand function to estimate the overall demand price elasticities of cigarettes, alcohol, tea and coffee, a seemingly unrelated regression analysis was used. The independent variables were annual consumption of cigarettes, alcohol, tea and coffee. The dependent variables were prices of and expenditures on cigarettes, alcohol, tea and coffee. RESULTS: The estimated own-price elasticities for cigarettes and alcohol are close to -0.726. The own-price elasticities for tea and coffee are less than those for cigarettes and alcohol. Hence, it is predicted that the NT$10 health tax on cigarettes will reduce cigarette consumption by a significant 13.19%. Analysis of cross-price elasticity reveals that alcohol is complementary to cigarettes. CONCLUSIONS: Taxation is an effective smoking control policy tool that not only helps to reduce consumption of cigarettes, but also reduces consumption of alcoholic beverages.

[Clinical and pathological analysis of IgA nephropathy with acute kidney injury].

OBJECTIVE: To investigate the incidence, etiology, clinico- pathological characteristics and prognosis in primary IgA nephropathy (IgAN) children with acute kidney injury (AKI). METHOD: Retrospective analysis of the clinical and pathological manifestations and follow-up results of 19 Chlidren, who were associated with AKI in 196 cases of children with IgA nephropathy treated in our department from January, 1996 to Jun, 2012 was performed. RESULT: (1) The 19 cases associated with AKI accounted for 9.7% of all 196 Chlidren with IgAN. Within the 19 cases, there were gross hematuria in 17 cases, massive proteinuria in 16 cases, hypoalbuminemia in 10 cases, edema in 10 cases and hypertension in one case. The peak serum creatinine was from 94.5 µmol/ L to 282 µmol/L. (2) Histological changes: with the formation of crescent in 10 cases, diffuse endocapillary proliferation in 5 cases, 15 cases had renal tubular injury, 10 cases had red blood cell and protein cast, 1 case with acute interstitial nephritis. (3) The cause of IgA nephropathy with AKI: 13 patients had severe glomerular damage, including crescentic glomerulonephritis and diffuse endocapillary proliferation; 1 case was complicated with acute interstitial nephritis after being treated with antibiotics, 2 patients had decreased glomerular filtration rate because of taking benazepril or oral indomethacin, 1 case with renal tubular injury induced by gross hematuria, and the other two cases the reason was not clear. (4) Multivariate Logistic regression analysis showed that massive proteinuria was independent risk factor of IgAN in children with AKI (OR=27.370, 95% confidence interval was 3.151-237.740, P<0.01). (5) None of the patients were on dialysis, steroid therapy was used in 13 cases (including 7 cases of methylprednisolone pulse therapy), 6 cases were treated with combined cyclophosphamide treatment. Except 1 cases no significant improvement, the renal functiones of all patients recovered or improved within 1-2 months after treatment. Follow-up period was from 1 month to 7 years, 3 cases had renal function improved, but 2 cases were lost to follow-up for 3 years and then entered the chronic renal failure, 1 case had renal function loss after 32 months and repeated renal biopsy showed glomerular sclerosis of 32% during the follow-up period. CONCLUSION: In children with IgAN, AKI accounted for about 10%, except glomerular severe lesion, the onset of AKI is also relevant to clinical medication and repeated gross hematuria, and the heavy proteinuria is an independent risk factor. Based on clinical observation, the short-term prognosis of IgAN children with AKI is optimistic.

Predictive capacity of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma.

PURPOSE: The International Prognostic Factor Index has been shown to predict the outcome of patients with predominantly B-cell lymphomas classified using traditional classifications, including the Working Formulation, but its prognostic importance has not been tested in a cohort of patients with exclusively T-cell lymphomas. This study was conducted to evaluate the prognostic significance of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Seventy-eight patients (48 men and 30 women) with PTCL seen at a single institution between 1985 and 1995 were included in the analysis. The morphology and immunocytochemistry of all the original biopsy specimens were reviewed by a single pathologist and classified using the Revised European-American Lymphoma (REAL) classification. The International Prognostic Factor Index, as well as clinical and biochemical parameters, were evaluated by univariate and multivariate analyses to determine their association with patient outcome. RESULTS: The International Prognostic Factor Index strongly predicted survival when all patients were included in the analysis (P < .001). For patients < or = 60 years, the age-adjusted International Index significantly predicted long-term survival (P = .0218). For patients older than 60 years, the age-adjusted International Index also significantly predicted survival (P = .002). Liver involvement (P = .006) and bone marrow involvement (P = .014) were also significant prognostic factors in the univariate analysis, but only the International Index remained significant in the multivariate analysis (P = .001). CONCLUSION: The International Prognostic Factor Index, which significantly predicts outcome in patients with aggressive/intermediate-grade B-cell lymphomas, has similar prognostic importance in patients with PTCL.

Lymphocyte recovery after allogeneic bone marrow transplantation predicts risk of relapse in acute lymphoblastic leukemia.

Allogeneic blood and marrow transplantation (BMT) is curative for many patients with high-risk and relapsed acute lymphoblastic leukemia (ALL). However, relapse is an important cause of post-transplantation failure, and there are no reliable markers to predict relapse. A retrospective review of patients with ALL who underwent matched related allogeneic BMT was carried out to examine whether the rate of lymphocyte recovery after transplantation had any prognostic value in ALL. The absolute lymphocyte count (ALC) at days 21 and 30 after transplantation was obtained for 43 patients who received transplants during an 18-year period. Patients with an ALC of 175 x 10(6)/l or less on day 21 were more likely to relapse than those with ALC greater than 175 x 10(6)/l (relative risk, 4; 95% confidence interval, 1.5-11.2). Patients with slower lymphocyte recovery had significantly lower relapse-free survival than those with faster recovery (P=0.0028). There was also a trend toward poorer overall survival among those with a slow lymphocyte recovery (log-rank test; P=0.028). The rate of lymphocyte recovery is prognostic in patients with ALL undergoing allogeneic BMT, and this should be integrated with other predictors to identify patients at high risk of relapse. Such patients could be considered for interventions aimed at prevention of relapse, including rapid withdrawal of immunosuppressive medication or donor lymphocyte infusion.

Hodgkin's disease manifesting as Hashimoto's thyroiditis.

Hodgkin's disease can be manifested in ways other than lymphadenopathy. Two patients had symptoms related to thyroid enlargement and were initially believed to have Hashimoto's thyroiditis on the basis of markedly elevated thyroid antibody titers. Involvement of the thyroid region by Hodgkin's disease was eventually diagnosed.

Light scatter and cell surface properties of murine megakaryocyte progenitor cells.

The characteristics with respect to light scatter and cell surface properties of megakaryocyte colony-forming cells (CFU-Meg), growing in serum-free agar cultures, have been determined. Mouse bone marrow cells were fractionated using a light-activated cell sorter (FACS) either on the basis of light scatter or after staining with a fluorescein isothiocyanate (FITC)-labeled lectin or monoclonal antibody. After staining and sorting, the recovery of CFU-Meg was about 50%. In the unsorted controls 29 +/- 2 CFU-Meg/10(5) cells were observed. The forward (FLS) and perpendicular (PLS) light scatter intensities of CFU-Meg were very similar to those of spleen colony-forming cells (CFU-S) and early progenitor cells. The average diameter of the CFU-Meg as determined by the FLS intensity profile was about 7.5 microns. Wheat germ agglutinin binding of CFU-Meg was high, indicating a high sialic acid content of the cell surface. Expression of the differentiation antigen Pgp-1 on the CFU-Meg as determined by indirect immunofluorescence with the rat monoclonal antibody I42/5.1 was moderate. Pgp-1 expression was lower than the Pgp-1 expression of granulocyte/macrophage progenitors (CFU-C) or granulocytes. It is concluded that the light scatter and cell surface properties of CFU-Meg are similar to those of CFU-S and early committed progenitors.

Influence of lithium on proliferation of hematopoietic stem cells.

We studied the effect of lithium on normal marrow hematopoiesis by determining the numbers of pluripotential (CFUS) and committed stem cells (CFUC, CFUE and BFUE) after in vitro and in vivo exposure to lithium. In the presence of 1 meq/L lithium in vitro, marrow CFUS and CFUC were increased; higher concentrations (greater than or equal to 5 meq/L) were inhibitory. Marrow CFUE and BFUE were decreased at concentrations of lithium greater than or equal to 0.5 meq/L. In vivo (0.5-5.0 meq/L i.p.), lithium produced similar results to those obtained in vitro with striking CFUC enhancement. Serum from these lithium-treated mice contained increased colony stimulating factor (CSF). In the Dexter continuous marrow culture system, lithium stimulated increased CFUC production from the non-adherent fraction. These in vitro nd vivo studies document lithium's ability to modulate hematopoiesis by influencing pluripotential and committed stem cell proliferation and differentiation towards granulopoiesis, apparently at the expense of erythropoiesis. Mechanisms of this modulation are discussed.

Modulation of murine in vitro erythroid and granulopoietic colony formation by ouabain, digoxin and theophylline.

Ouabain has been shown to increase the number of clonally derived erythroid stem cells, CFUE and BFUE, from normal murine bone marrow. We report here that digoxin and theophylline also enhance erythroid stem cell colony formation, in the presence of suboptimal concentrations of erythropoietin (Ep) (0.01 IU/ml) in methylcellulose culture. Both digoxin and theophylline increased CFUE colony formation optimally at 10(-8) M (29-81% respectively). The increase in BFUE colony formation occurred at 10(-10) M (35-76% respectively), suggesting that BFUE are more sensitive to the enhancing properties of these compounds. In addition, digoxin theophylline and ouabain were effective inhibitors of clonally derived granulocyte-macrophage progenitor cells, CFUC, from normal murine marrow plated in double layer agar in the presence of 10% L-cell conditioned medium (LCM). The degree of reduction in colony formation by CFUC ranged from 11% to 100%. Digoxin and theophylline were inhibitory for CFUC in the range of 10(-2) to 10(-12) M; however, ouabain was inhibitory over a broader concentration range of 10(-4) to 10(-18) M, suggesting that ouabain has a greater influence on committed hematopoietic progenitor cell colony formation. Both ouabain and digoxin have the property of binding to Na+/K+ATPase. This may mediate the alteration of hematopoietic differentiation. Theophylline, an adenyl cyclase inhibitor, may act through alterations in cyclic nucleotide levels. These studies further indicate that digoxin, theophylline and ouabain may serve as useful tools in elucidating the underlying mechanisms of how specific growth factors influence hematopoietic growth and differentiation.

Lithium stimulates the recovery of granulopoiesis following acute radiation injury.

Lithium (Li) is a known stimulator of steady-state granulopoiesis, influencing both pluripotential (CFUS) and granulocyte-macrophage committed stem cell (CFUGM) populations. Li has therefore been suggested to be an effective agent to reduce the neutropenia that often is seen after either cytotoxic chemotherapy or radiotherapy protocols. In this report, we have examined bone marrow and spleen cells for their recovery patterns of CFUS, CFUGM, CFUE, BFUE and 59Fe-incorporation, along with the usual peripheral blood indices (packed red cell volume, WBC and differential) from mice administered Li after receiving 200 rad whole body irradiation. Li increased granulopoietic recovery as measured by significant elevations in both marrow and spleen derived CFUGM compared to those values obtained from radiation controls. Significant elevation in the WBC, consisting mainly of neutrophils, was also observed. Bone marrow and splenic derived erythroid stem cells (CFUE, BFUE) and % 59Fe-incorporation measured from peripheral blood, femur and spleen were all slightly reduced, but not to a significant degree to alter the packed red cell volume. The CFUS populations from both irradiated groups (control and Li-treated) were depressed when compared to normal non-irr controls and this degree of suppression was greater in the Li-treated group. These results document the ability of Li to stimulate the recovery of granulopoiesis after radiation-induced hematopoietic injury and suggest Li may be useful in ameliorating the neutropenia that can often develop after routine radiotherapy protocols.

Lithium stimulated in vitro megakaryocytopoiesis.

We have investigated the effects of lithium on the proliferative potential of murine megakaryocyte stem cells (CFUMeg) in vitro and on circulating platelet levels in vivo. At optimal levels of megakaryocyte-colony stimulating factor (Meg-CSF) (10%) concentrations of 0.5, 1.0 and 3.0 meq/L augmented CFUMeg numbers. Significant increases of 133% and 125% over control levels were observed at 1.0 and 3.0 meq/L, respectively. At suboptimal concentrations of Meg-CSF (1.0%), Li effected a maximum increase of 200% over control levels at 1.0 meq/L suggesting a greater sensitivity of CFUMeg to stimulatory factors in the presence of Li. To better define the mode of action of Li, heterogenous bone marrow was separated into adherent and non-adherent cell populations and cultured in the presence of Li. Non-adherent cells cultured in the presence of 0.5, 1.0 and 3.0 meq/L Li showed significant increases in CFUMeg over non-adherent cells cultured without Li. These results suggest a direct effect of Li on CFUMeg. Cells cultured from the adherent cell population also responded to Li with enhanced CFUMeg numbers. This response may be a direct stem cell effect or an indirect effect via the production of endogenous Meg-CSF. One meq/L of Li when injected i.p., produced a thrombocytosis from days 4 through 15, with a maximum at 6 days post-Li treatment. These results suggest Li is an effective agent for stimulating megakaryocytopoiesis and has both direct and possibly indirect effects on the megakaryocyte stem cell.

Effect of methotrexate on cell cycle and DNA synthesis of astrocytes in primary culture: flow cytometric studies.

Relatively pure population of astrocytes in primary culture were examined by flow cytometry at various time intervals after exposure to 1, 10 and 100 microM of methotrexate (MTX). The percentage population of cells in different phases of the cell cycle was determined using propidium iodide (PI) to measure cellular DNA content. DNA synthesis was assessed by measuring the fluorescence intensity of FITC-conjugated antibody to bromodeoxyuridine (BrdUrd). The two parameters were correlated to determine the location of BrdUrd-incorporating cells within the cell cycle. Exposure of astrocytes to MTX caused a consistent increase in number of cells in S-phase which correlated with the increase in BrdUrd incorporation. These studies provide supportive evidence that the astrogliosis seen in MTX encephalopathy may be due to a primary involvement of astrocytes.

Effect of methotrexate on glial fibrillary acidic protein content of astrocytes in primary culture.

We have recently reported that methotrexate (MTX) causes degenerative as well as reactive-like astroglial changes and alters the cell cycle kinetics of astrocytes in vitro. To further characterize the nature of the reactive-like changes that were noted by light and electron microscopy following MTX exposure, the glial fibrillary acidic protein (GFAP) content of astrocytes in culture was investigated by enzyme-linked immunosorbent assay, flow cytometry and double-immunofluorescent staining. An increase in GFAP content which did not correlate with drug dosage or DNA synthesis was noted in the MTX-treated cultures. It is postulated that this increase in GFAP content of astrocytes reflects an adaptive response to MTX-induced injury and partly explains the gliosis that is seen in methotrexate encephalopathy.

Local control and complications after radiation therapy for primary orbital lymphoma: a case for low-dose treatment.

Orbital involvement at the time of initial presentation is unusual in non-Hodgkin's lymphoma. In an effort to identify potential ways of improving the radiotherapeutic management of this disease, the records of 22 patients were reviewed retrospectively. All had biopsy-proven orbital non-Hodgkin's lymphoma, and the minimal, median, and maximal durations of follow-up in surviving patients were 4.8 years, 7.0 years, and 17.4 years, respectively. Permanent local control was achieved in 21 of the 22 patients (96%). Complications were scored according to a grading scheme in which grade 1 was the least significant complication and grade 4 was blindness as a result of radiation therapy. Of the 12 patients who received a radiation dose less than 35 Gy, 6 developed a grade 1 or grade 2 complication. Of the 10 patients treated with greater than or equal to 35 Gy, 6 experienced a complication, 1 of whom had a grade 4 complication resulting in blindness and another who developed a severe keratitis, which was scored as a grade 3 complication resulting in decreased visual acuity. At last follow-up, 10 patients were alive at 4.8 to 17.4 years after completion of radiation therapy, 4 had died of intercurrent disease at 3 months to 10.6 years, and 8 had died of disease at 3 months to 15.8 years. Actuarial survival for the entire group was 75% at 5 years and 48% at 10 years. Survival in patients with Stage I AE disease (lymphoma confined to orbit) at presentation was 87% at 5 years and 50% at 10 years, and survival in patients with Stage II A through Stage IV disease was 36% at 5 years and at 10 years. Primary orbital lymphoma is an indolent disease characterized by prolonged survival after radiation therapy. Excellent local control can be achieved with radiation doses of 20 Gy to 35 Gy. Higher doses may result in an increased risk of complications.

Radiation therapy for diabetes insipidus caused by Langerhans cell histiocytosis.

Hypothalamic-pituitary radiation therapy has been the standard treatment for the diabetes insipidus of Langerhans cell histiocytosis. The goal of this study was to assess the role of radiation therapy in Langerhans cell histiocytosis-associated diabetes insipidus and to compare the results with nonirradiated controls. Forty-seven patients with pathologically confirmed Langerhans cell histiocytosis were diagnosed with diabetes insipidus between 1950 and 1989 and were treated at the Mayo Clinic. These patients were divided into two groups on the basis of treatment for the diabetes insipidus: The first group (radiation group) included 30 patients (28 of whom were evaluable for response) who received hypothalamic-pituitary radiation therapy, and the second group (control group) included 17 patients who did not. A partial response to treatment was defined as a reduction in vasopressin dosage or improvement in computed tomography (CT) or magnetic resonance imaging (MRI). A complete response was defined as no further need for vasopressin therapy or normalization of CT or MRI. End points analyzed included treatment response, patient characteristics, morbidity, dose-response relationship, and survival. Patient characteristics of the two groups were similar except for age and lung involvement, both of which were significantly less in the radiation group. Thirty-six percent of patients (10 of 28) in the radiation group responded to hypothalamic-pituitary radiation therapy (22% complete response and 14% partial response), whereas none in the control group responded. Five of the six complete responders were irradiated within 14 days of the diagnosis of diabetes insipidus. The mean dose used in the responding and nonresponding patients was 11.2 and 10 Gy, respectively. Three of five patients (60%) treated with more than 15 Gy responded compared to seven of 23 (30%) treated with less than 15 Gy. Eight of the 10 responders (80%), compared to 16 of 35 nonresponders (46%), were female. Only one in 20 patients with concomitant lung histiocytosis responded. Complications of therapy may include insufficiency in other hypothalamic-pituitary axes in the treated patients. Actuarial survivals at 5, 10, 20, and 40 years for the entire group were 80%, 78%, 75%, and 65%, respectively, with a median follow-up in living patients of 14.7 years.

Primary cutaneous large cell lymphomas. Morphologic, immunophenotypic, and clinical features of 20 cases.

The morphologic, immunophenotypic, and clinical characteristics of 20 cases of primary cutaneous large cell lymphoma were analyzed. Immunoperoxidase stains in paraffin sections indicated B-cell phenotype in 14 cases and T-cell phenotype in six cases. By the Kiel classification, the B-cell lymphomas were classified into the following categories: follicular centroblastic (three patients), centroblastic/centrocytic with a predominance of large centrocytes (two patients), centroblastic (seven patients), and immunoblastic (two patients). The T-cell lymphomas (six cases) were all categorized as pleomorphic medium and large cell type. Three of these had an angiocentric growth pattern. The lymphocyte activation marker CD30 was expressed in three of the 20 cases. Among these 20 patients, the clinical course was remarkably variable. The only clinical or pathologic feature with prognostic significance was multicentricity of the skin lesions. All five patients with multifocal or disseminated skin lesions died within 13 months of their initial presentation; the median survival was 7 months. Most of the patients with localized skin lesions had an indolent clinical course with a median survival of 107 months. These results suggest that multicentricity of the skin lesions and necrosis are closely linked and are important prognostic features in cutaneous large cell lymphoma.

Vancouver hybrid: preliminary experience in the treatment of Hodgkin's disease in childhood and adolescence.

OBJECTIVE: To describe our preliminary experience with 19 young patients with newly diagnosed Hodgkin's disease who received the Vancouver hybrid chemotherapeutic regimen. DESIGN: We summarized the characteristics of our 19 study patients, the treatment administered (between June 1988 and June 1992), and the outcome. RESULTS: The Vancouver hybrid, which consists of mechlorethamine, vincristine sulfate (Oncovin), procarbazine hydrochloride, prednisone, doxorubicin hydrochloride (Adriamycin), bleomycin, and vinblastine sulfate (MOPP/ABV), was based on the hypothesis of preventing drug resistance by early introduction and alternation of all active agents and was aimed at decreasing the severity and frequency of treatment-related complications. Of our 19 patients with Hodgkin's disease (age range, 6 to 20 years) treated with this regimen, 2 had clinical stage I disease, 10 had stage II, 6 had stage III, and 1 had stage IV. Only two patients had systemic symptoms, and nodular sclerosis was the most common histologic feature. Patients were given four to eight cycles of chemotherapy, depending on the clinical stage of disease. In addition, 10 patients received irradiation, including 6 of 9 patients with bulky disease. In all patients, complete remission was achieved. After a median follow-up of 3.3 years, only two patients had had a relapse; both underwent autologous bone marrow transplantation and were alive and well with no evidence of disease at last follow-up. The treatment was well tolerated, and delivery of treatment was excellent. The only severe toxicity was myelosuppression; 8 patients experienced a total of 15 episodes of fever and neutropenia that necessitated hospitalization and antibiotic therapy, but no systemic infections were confirmed during 104 cycles of therapy. CONCLUSION: The MOPP/ABV hybrid is an effective and well-tolerated therapy in most young patients with Hodgkin's disease. Long-term monitoring is needed to evaluate late effects.

Mayo Clinic experience with allogeneic and syngeneic bone marrow transplantation, 1982 through 1990.

Between April 1982 and July 1990, 101 patients underwent allogeneic or syngeneic bone marrow transplantation at the Mayo Clinic. This patient population consisted of 30 with acute nonlymphocytic leukemia, 25 with acute lymphoblastic leukemia, 29 with chronic granulocytic leukemia, and 17 with other diseases (aplastic anemia in 7, myelodysplastic syndrome in 5, and lymphoma in 5). The results achieved in our patients who underwent transplantation in first complete remission of both acute nonlymphocytic leukemia and acute lymphoblastic leukemia compare favorably with previously reported results. Only 1 of 15 patients (7%) with acute nonlymphocytic leukemia and 2 of 8 patients (25%) with acute lymphoblastic leukemia who underwent transplantation in first complete remission had a relapse. Thus, we recommend early bone marrow transplantation during initial complete remission for patients with either of these disorders who have adverse prognostic factors. In contrast, of 12 patients with either acute nonlymphocytic leukemia or acute lymphoblastic leukemia who underwent transplantation during relapse, 11 died within 6 months. Therefore, such patients should be offered new experimental treatments. Our patients with chronic granulocytic leukemia fared better when they underwent transplantation early during the course of their disease rather than during the accelerated or blast phase. Prospective studies are needed to determine the best approach in these patients.

Lymphoma in soft tissue: a clinicopathologic study of 19 cases.

The authors retrospectively reviewed 19 patients who presented with lymphoma as soft tissue masses, without evidence of lymph node or skin involvement. Sites of involvement included lower extremity (seven), upper extremity (six), chest wall (three), gluteal region (two), and frontal subgaleal region (one). Histological and immunophenotypic studies revealed 12 large cell lymphomas (11 B cell and one T cell), two small noncleaved cell lymphomas (B-cell phenotype), and five low grade B-cell lymphomas (two small lymphocytic and three follicular mixed lymphomas). Patients with large cell lymphoma, including seven patients with stages I and II and five patients with stage IV, were treated with anthracycline-based chemotherapy, with or without radiation therapy. One half of these patients are dead of disease, including four of seven with low stage disease. The two patients with small noncleaved cell lymphoma had stage IE disease and were treated with chemotherapy; one died at 11 months, and the other is alive and disease free at 65 months. Patients with low grade B-cell lymphoma included four stage IE patients who were treated with radiation and one stage IV patient treated with chemotherapy. Two patients are alive and disease free, and three are dead of unrelated causes. The authors conclude that malignant lymphomas initially diagnosed in soft tissues are most commonly large cell lymphomas with a B-cell phenotype.