Flow-cytometry detection of minimal DNA aneuploidy in mature lymphoid leukemias - comparison with metaphase and interphase cytogenetics

The relative DNA content of peripheral blood cells from 79 cases with lymphoid leukemias was analyzed by a dual-parameter flow cytometric analysis. The leukemia samples corresponded to: chronic lymphocytic leukemia (CLL) 40, CLL with more than 10% prolymphocytes (CLL/PL) 12, CLL mixed 9, prolymphocytic leukemia (PLL) 5, and B-cell lymphoma in leukemic phase 13. DNA aneuploidy was found overall in 26 (32.9%) of the cases and these corresponded to: 7 (17.5%) with CLL, 7 (58.3%) with CLL/PL, 4 (44.4%) with CLL mixed, 2 (40%) with PLL and 6 (46.2%) with B-cell lymphoma. There was a good correlation between DNA content and cytogenetics/fluorescent in situ hybridization in all but 2 cases as follows: 6 of 7 cases with diploid DNA had normal karyotype and only one had trisomy 12: 4 of 6 cases with hyperdiploid DNA had trisomy 12, one had tetraploidy and only one had a normal karyotype. Two cases were hypodiploid both by DNA and cytogenetic analysis. Our findings demonstrate a higher incidence of DNA aneuploidy in B-cell lymphoma in leukemic phase, PLL, and atypical CLL in comparison with typical CLL and a good correlation with cytogenetics. We conclude that flow cytometric DNA analysis represents a useful, sensitive, and rapid method to detect and monitor minimal changes of DNA content in leukemic lymphocytes without the need of short-term cultures.     

Characterization of cystic tumors of the pancreas: CT accuracy

PURPOSE: The purpose of this work was to evaluate the capabilities of CT to accurately characterize cystic tumors of the pancreas. METHOD: Two observers retrospectively evaluated the CT exams of 100 cystic masses of the pancreas, with pathological confirmation. The two observers, blinded about clinical information and the final diagnosis, tried to categorize the lesions according to well established morphologic features. Statistical analysis was performed to measure the agreement between each radiologist and the consensus diagnosis and to evaluate the usefulness of certain CT findings in differentiating one type of cystic pancreatic neoplasm from another. RESULTS: Serous cystadenoma was better diagnosed by CT [Youden misclassification index (Ymi) = 0.72] than mucinous cystic tumor (Ymi = 0.44) and solid pseudopapillary tumor (cystic variant) (Ymi = 0.47). CONCLUSION: As patients with previous history of pancreatitis were excluded from the study, CT findings allowed correct characterization of only 60% of cystic pancreatic masses. Among the remaining 40%, 15-20% of the wrong diagnoses could not be corrected by means of CT, given the patterns shown by the tumors. In 20-25% of the cases, a nonspecific diagnosis of cystic mass was made.     

Adoptive Immunotherapy With Tumor-Infiltrating Lymphocytes and Subcutaneous Recombinant Interleukin-2 Plus Interferon Alfa-2a for Melanoma Patients With Nonresectable Distant Disease: A Phase I/II Pilot Trial

Background: On the basis of our previous experience, we designed this study to determine the activity and toxicity of outpatient treatment with autologous tumor-infiltrating lymphocytes (TIL) together with intermediate-dose recombinant interleukin-2 (rIL-2) and low-dose recombinant interferon alfa-2a (rIFN-2a), for patients with metastatic melanoma.Methods: Between April 1992 and October 1994, we processed 38 melanoma samples derived from 36 patients with metastases. Proliferative cultures of expanded lymphocytes (TIL) were infused only once into patients with metastatic melanoma. rIL-2 was administered subcutaneously for 1 month, starting on the day of TIL infusion, at an escalating dose of 6–18 × 10⁶ IU/m²/day for the first week and at the maximum-tolerated dose for the subsequent 3 weeks and then, after a 15-day interval, for 1 week/month for 3 months. rIFN-2a was administered subcutaneously at 3 × 10⁶ IU three times each week until progression.Results: Of 38 melanoma samples, 19 (50%) resulted in proliferative cultures and were infused. The median number of expanded lymphocytes was 18 × 10⁹ (range, 1–43 × 10⁹), and the median period of culture was 52 days (range, 45–60). rIL-2 was administered at doses ranging between 6 and 18 × 10⁶ IU/m²/day. Toxicity was mild or moderate, and no life-threatening side effects were encountered. Two of 19 treated patients experienced complete responses of their metastatic sites (soft tissue), 10 had stable disease, and 7 showed progressive disease. The response rate was 11% (95% confidence interval, 2–35%).Conclusions: Outpatient treatment with TIL plus rIL-2 and rIFN-2a is feasible, although, within the context of the small sample size, the activity of the combination was no different from the reported activity of any of the components used alone.     

Antihypertensive drug therapy and hypoglycemia in elderly diabetic patients treated with insulin and/or sulfonylureas

We performed this case–control study to evaluate the risk of hypoglycemia associated with the use of antihypertensive drugs in older hospitalized diabetic patients treated with sulfonylureas and/or insulin. All diabetic patients admitted during 4 months in 1988, 1 month in 1991, 4 months in 1993 and 4 months in 1995 (n = 3477, mean age 71.4 ± 0.2 years, 1542 males and 1935 females) were enrolled in the study. During the four annual surveys 86 patients (mean age 71.1 ± 1.4 years, 33 males and 53 females) presented hypoglycemia during hospital stay. The patients who presented hypoglycemia were less frequently users of sulfonylureas and more frequently users of a combination of insulin and sulfonylureas. Use of antihypertensive drugs was similar in the two groups studied, and among potentially interacting drugs considered in the analysis, sulfonamides were more frequently used in patients who experienced hypoglycemia. Moreover, patients with hypoglycemia used a higher number of drugs, had a longer length of stay and had a greater prevalence of hypoglycemia as admission problem. Finally, although not significant, liver and renal diseases were more frequent among patients with hypoglycemia. In the multivariate analysis, contemporary use of insulin and sulfonylureas, liver disease and length of stay were significantly associated with hypoglycemia, while none of the antihypertensive drugs showed a significant association with the occurrence of hypoglycemia during hospital stay. Our results indicate that antihypertensive drugs do not increase the risk of hypoglycemia in elderly diabetic patients.     

Prevention by rolipram of concanavalin A-induced T-cell-dependent hepatitis in mice

Rolipram is a type IV phosphodiesterase inhibitor endowed with powerful immunomodulatory properties. In this study, we evaluated the effects of this drug on the development of the T-cell-mediated hepatitis inducible in mice by concanavalin A. The results indicated that prophylactic treatment with either 5 or 10 mg/kg rolipram injected intraperitoneally 24 h and 1 h prior to intravenous (i.v.) challenge with 20 mg/kg concanavalin A successfully ameliorated serological and histological signs of liver damage, so that the treated mice showed lower transaminase levels in the plasma and milder mononuclear cell infiltration of the liver as compared to vehicle-treated controls. Moreover, this effect was associated with profound modifications of circulating levels of cytokines released after concanavalin A injection, with the blood levels of interferon-gamma and tumor necrosis factor-alpha being significantly lower and those of interleukin-10 higher than those of the control mice. In particular, the increased blood levels of interleukin-10 might play an important role in the anti-hepatitic effects of rolipram as coadministering this compound with anti-interleukin-10 monoclonal antibody significantly reduced its anti-inflammatory action. These results suggest that rolipram may be useful in the clinical setting for the treatment of cell-mediated immunoinflammatory diseases such as immunoinflammatory hepatitis.     

Early MRI findings in Creutzfeldt-Jakob disease

We describe the MRI changes preceding the onset of myoclonus in two patients whose post-mortem examination confirmed the diagnosis of Creutzfeldt-Jakob disease (CJD). MRI showed changes in the striatum early in the course of CJD (2–6 months after the onset of apathy, interpreted as depression, and 1–2 months before the onset of further clinical symptoms). Only in one patient did electroencephalography record the typical triphasic sharp-waves, 1 month after MRI.     

Bulbectomy Enhances Neurogenesis and Cell Turnover of Primary Olfactory Neurons But Does Not Abolish Carnosine Expression

Primary olfactory neurons located in the olfactory neuroepithelium project to the ipsilateral olfactory bulb and undergo a continuous process of neurogenesis and differentiation. We describe, in the adult rat, the kinetics of proliferation, differentiation and survival of primary olfactory neurons either in the presence or absence of their target, the olfactory bulb. The experimental design included unilateral bulbectomy, coupled with a single bromodeoxyuridine pulse 35 days after surgery. The rate of proliferation and survival of olfactory neurons was then examined by immunohistochemistry for bromodeoxyuridine, and the differentiation status by in situ hybridization for calmodulin messenger RNA in immature and mature olfactory neurons and immunohistochemistry for the dipeptide carnosine in mature olfactory neurons. We show that primary olfactory neurons can synthesize carnosine in the absence of the olfactory bulb. However, the number of carnosine-immunopositive neurons in the absence of their target is dramatically reduced to less than one-fourth, whereas the number of olfactory neurons expressing calmodulin messenger RNA is only slightly reduced. The numeric reduction of camosine-positive neurons in the target-deprived neuroepithelium is correlated with a dramatic reduction in the survival rate of olfactory neurons, since newly generated olfactory neurons are completely lost 35 days after the bromodeoxyuridine pulse. In contrast, in the normal olfactory neuroepithelium almost one-third of newly generated olfactory neurons survive 35 days after the bromodeoxyuridine pulse. On the whole, these data indicate that most of the primary olfactory neurons have a short lifespan but that once they have connected with the olfactory bulb they may persist longer, and suggest that throughout adulthood olfactory neurons are overproduced, differentiate independently from their target, and then undergo a process of target-induced neuronal selection.     

DSM-III mental disorders in general medical sector: a follow-up and incidence study over a two-year period

Summary In three general medical settings (general practice, hospital medical wards and emergency rooms) about 20% of the adult attenders had a DSM-III mental disorder, mainly in the area of affective and anxious disorders. Some of these disorders were quite severe. Of those cases reassessed 1 year and 2 years after the first interview, less than a quarter reached a no-diagnosis status. The chronicity of most cases dependent on the interplay not only of either relapse or duration of the main disorder but also of comorbidity and incidence of new disorders. A high incidence of more transient disorders in subjects who were well at first assessment was also found.