Radiation-induced gadd45 expression correlates with clinical response to radiotherapy of cervical carcinoma

BACKGROUND: Recent work has identified a category of genes devoted to the control of genomic stability and prevention of cellular evolution. They encode components of cell cycle checkpoint, i.e., regulatory pathways committed to ordered cell cycle transition and fidelity of replicated DNA under adverse environmental conditions, such as those following exposure to genotoxic agents. Gadd45 belongs to the class II family of DNA damage-inducible (DDI) gene, and its role in DNA repair has been proved in many experimental models. The aim of our study was to correlate gadd45 radio-induction with the responsiveness to radiotherapy of cervical carcinomas, a type of cancer most commonly treated with radiotherapy alone. METHODS: By means of a competitive polymerase chain reaction strategy, we compared in 14 patients the gene expression levels before and during external beam radiotherapy, when a dose ranging from 18 to 25 Gy was delivered to the target. RESULTS: We found a correlation between the lack of gadd45 induction and a good clinical response to radiotherapy, in terms of both local control and disease-free survival. CONCLUSION: Our results support the measure of the induction of gadd45, and possibly of other genes required for regulated G1-S checkpoint, as a method useful for prognostic evaluation of cervical carcinoma patients.     

In vitro hematopoiesis in patients with malignant lymphoma during active disease and at complete clinical remission after chemotherapy

Malignant lymphomas are neoplastic diseases of lymphoid cells, which usually originate in the lymph nodes. During the last two decades, significant progress has been made in the characterization of chromosomal and molecular alterations in these malignancies. To date, however, the composition and function of the hematopoietic system in this group of hematological disorders is still not fully understood. In the present study, we have determined the progenitor cell content in 10 patients with diffuse large-cell lymphoma (DLCL) and characterized the proliferation of these cells in long-term marrow cultures. We have also addressed some issues regarding the composition and function of the hematopoietic microenvironment in this malignancy. All the patients included in this study showed normal hematological parameters in peripheral blood, both before and after chemotherapy, however, significant hematopoietic alterations were consistently observed. As compared to normal subjects, lymphoma patients showed a 35% reduction in progenitor cell numbers, including myeloid, erythroid and multipotent progenitors. The in vitro proliferation of these cells was also deficient, since their levels in long-term marrow cultures were significantly lower than those observed in normal bone marrow cultures. Fibroblastic progenitors were reduced by >50% and this correlated with a deficient adherent cell layer development in culture. A reduction was also seen in the levels in culture supernatant of the stimulatory cytokines Stem Cell Factor and Interleukin-6. Interestingly, all the hematopoietic alterations mentioned above were still present in patients at complete clinical remission after chemotherapy. Thus, in the present study we have demonstrated significant in vitro deficiencies in the composition and function of the hematopoietic system in patients with diffuse large-cell lymphoma, both during active disease and at the time of complete clinical remission.     

Second lethal events associated with treatment for Hodgkin's disease: a review of 2980 patients treated in a single Mexican institute

Presence of second neoplasms and cardiac toxicity has been recognized as potential late lethal second events in patients treated for Hodgkin's disease. However, most reports analyze these association independently. We reviewed 2980 cases of patients treated during 1970-1995 with long-term follow-up (> 4 years) in an attempt to identify all late events in Hodgkin's disease secondary to the treatment or those which are unrelated. Three hundred and ten patients died, and of these 156 were secondary to relapse and tumor progression. Death associated second tumors and cardiac events were increased 37 fold and 29 fold respectively compared to the general population. The risk factors for this complications did not differ to previous reports and included alkylating agents and/or radiotherapy for second neoplasms and anthracycline therapy and radiotherapy for cardiac toxicity. Moreover, 61 patients died secondary to non-related events. Nevertheless, at 20-years overall survival was 90 % (95 % confidence interval (CI): 78 % to 97 %) and event free survival was 88 % (95 % CI: 76 % to 96 %) for these patients. Thus, second events, fatal in most cases, should be considered as an expected risk to the treatment in patients with Hodgkin's disease; the proposed modifications of therapy may indeed be useful to avoid or diminish these complications in the future.     

PAR village. Specialized intervention for cocaine abusing women and their children.

Operation PAR in St. Petersburg received National Institute on Drug Abuse support in 1989 and state and local appropriations to establish PAR Village, a research demonstration program for treatment of cocaine abusing women with young children. Adjacent to PAR's residential therapeutic community, it includes 14 housing units and a day-care center for infants and children. Women live with their children while receiving long-term residential care. The program is being systematically evaluated by researchers from the University of South Florida Department of Psychiatry and Behavioral Medicine. Retention in treatment and post-discharge outcomes of the women are compared with those involved in the standard program where children remain in the community with relatives or are placed in foster care. Preliminary results suggest the demonstration program increases retention in treatment.     

Hodgkin's disease: summary of twenty years' experience.

BACKGROUND. A retrospective analysis on HODGKIN'S DISEASE (HD) was finalized to see if changing the management and therapy during the years we improved the cure rate of lymphomas and reduced the incidence of side effects due to therapy. Up to twenty years' experience was based in two major therapeutic periods: the first included patients observed between 1970 and June 1980 and the second between July 1980 and December 1987. Significant differences between the two periods were the reduction of splenectomies as staging procedure, the reduction of radiation dose and extension and the sequential use of MOPP/ABVD instead of MOPP alone. METHODS. The analysis included all patients observed over the twenty years under study by looking to the differences concerning response to therapy, survival, relapse-free survival and major consequences due to therapy, namely death not directly related to lymphoma. 377 pts entered the first period and 193 the second one with a minimum follow-up of 4 years. RESULTS. Significant differences were recorded on CR rate, 80.9% vs 90.5%, respectively (p = 0.0024) and deaths in CR, 15.1% vs 2.6%, respectively (p = 0.000). The overall survival shows a probability of 60% and 83% at 11 years for the first and the second group, respectively (p = 0.000) being the probability of survival of 50% at 20 years for the first group of pts. The probability of being in remission is similarly of 79% and 78%, for the first and second group, respectively. The risk of death in remission accounting all causes not related to lymphoma shows a 17% probability vs 6% at 11 years (p = 0.006) for the first and second group, respectively, being 38% for the former group at 20 years. The most frequent single cause of death in remission was secondary leukemia which was recorded in 14 pts on the group of pts observed between 1970 and 1980, all splenectomized and treated by MOPP and extensive radiotherapy. CONCLUSIONS. The modifications of therapy of HD have produced improvements concerning the prognosis of pts; these improvements are due mainly to the reduction of late side effects such as acute leukemia and second solid tumor, and to the increase of remission rate and cure rate of the lymphoma.     

Assessment of hyperemia in acute appendicitis: Comparison between power Doppler and color Doppler sonography

The purpose of our study was to compare power Doppler sonography (US) and conventional color Doppler US in the diagnosis of acute appendicitis by revealing local signs of hyperemia. One hundred consecutive patients (46 males and 54 females, ages 7–61 years; mean, 24.7 years) with clinically suspected acute appendicitis were prospectively examined with power Doppler US and conventional color Doppler US. Of 38 patients who subsequently underwent surgery, appendicitis was proven in 34. The remaining 62 patients who were not submitted to surgery had no clinical evidence of appendicitis over a 2- to 6-month follow-up. At gray-scale US, the appendix was visualized in 30 (88.2%) of the 34 cases with pathologically proven acute appendicitis. Power Doppler US depicted a moderate to marked hypervascularity of the appendiceal wall and surrounding mesoappendix in 28 (93.3%) of these 30 patients. At conventional color Doppler US, flow signal within the appendiceal wall and surrounding mesoappendix was shown in only 21 (70%) of 30 cases (P<0.05). No false-positive diagnosis was made at either power or color Doppler US among the 62 patients without appendicitis. Power Doppler US is more sensitive than conventional color Doppler imaging for revealing signs of local hyperemia in acute appendicitis.     

Spastic paraplegia,epilepsy, and mental retardation in several members of a family: A novel genetic disorder

We report on a family in which an association between spastic paraplegia and epilepsy has been observed. This disorder is an autosomal dominant trait with incomplete penetrance and variable expressivity. The onset was limited to the first four decades of life; the symptoms were typically those of progressive weakness and spasticity of lower limbs. Epilepsy was present in members of three of the four generations on whom we have information. The concomitance of spastic paraplegia and epilepsy in several members of the same family is unlikely to be fortuitous and probably represents the pleiotropic effect of a single mutant gene. © 1993 Wiley-Liss, Inc.     

Arthroscopic reconstruction of the anterior cruciate ligament with Leeds-Keio ligament in non-professional athletes

We report our experience using the Leeds-Keio artificial ligament for anterior cruciate ligament (ACL) reconstruction. The study relates the results of the first 40 patients subjected to arthroscopic reconstruction of the ACL with a Leeds-Keio ligament, with a mean follow-up of 73 months. No associated peripheral procedures were carried out on any patient. The average age of the patients at the time of the operation was 31 years (range 26–35 years). The rehabilitation protocol followed by all patients aimed at resumption of sport 4 months after the operation. Clinical assessment included IKDC and the Lysholm scoring scale. The KT-2000 system was used for instrumented evaluation of joint laxity. All patients underwent a radiographic check-up. Clinically there were 55% excellent or good results when using the IKDC scale, while with the Lysholm score, satisfactory results were obtained in 80%. Complete post-traumatic rupture of the ligament was observed in three patients. No patient suffered an episode of either hydrarthrosis or reactive synovitis, which indicates good tolerance to the ligament. The radiographic evaluation of the operated knees showed a close correlation between the appearance of degenerative phenomena and performance of arthroscopic meniscectomy. The results achieved with the Leeds-Keio artificial ligament 5 years after application, although not completely satisfactory and inferior to those obtained with autologous biological ligaments, should be considered an encouragement to promote new efforts in this interesting research field.     

Recurrent placenta previa

Among a group of 33 135 women who delivered at Beilinson Medical Center, Israel, during the years 1968 to 1978, recurrent placenta previa occurred in 3.2% of the women, i.e., 6 times higher than the incidence of placenta previa in the general population (0.5%). Analysis of the data revealed that women over 36 yr of age with a history of placenta previa are at risk for recurrent placenta previa. Maternal and perinatal morbidity and mortality were similar in cases of single and recurrent placenta previa.     

A structure-activity study of sympathomimetic amines on the beta-adrenoceptors of guinea-pig trachea

1. The relative activities of a large number of sympathomimetic amines were estimated on the beta-adrenoceptors of the guinea-pig tracheal chain preparation. Concentrations which produced half-maximal responses were measured for each drug and the maximum responses were also noted and expressed as a percentage of that produced by isoprenaline.2. The relative activities of the amines generally decrease with loss of hydroxyl groups from the structure, and amines with less than two hydroxyl groups produce little or no observable response.3. The affinity constants of the partial agonists and antagonists were measured. The hydroxyl group on the beta carbon atom of the side chain, N-alkyl groups and an alpha carbon methyl group increase affinity, whereas the p-phenolic group decreases affinity. The m-phenolic group does not seem to affect affinity.4. By comparing the effects of groups on affinity with their effects on activity, it was deduced that N-alkyl groups, m- and p-phenolic groups and probably also the beta carbon hydroxyl group increase efficacy. Alpha carbon methylation appears to reduce efficacy.