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PubMed1985

Hypoplastic anemia in B cell chronic lymphocytic leukemia: evolution of T cell-mediated suppression of erythropoiesis in early-stage and late-stage disease.

To define further the role of marrow T suppressor lymphocytes in the pathogenesis of the hypoproliferative anemia in all Rai clinical stages of B cell chronic lymphocytic leukemia (CLL), marrow erythroid progenitor cell (CFU-E and BFU-E) frequency, marrow T gamma lymphocyte frequency per 1,000 nucleated marrow cells, and T cell-erythroid progenitor cell interactions were examined in 30 CLL patients and normal control subjects. As compared with control subjects, decreased numbers of CFU-E and BFU-E were found in patient marrow depleted of neoplastic B cells in all Rai stages of the disease. As a group, Rai stage III through IV patients with or without aplasia (CLL-aplasia) had significantly fewer CFU-E and BFU-E than did Rai O through II stage patients. The numbers of T gamma cells infiltrating CLL marrows were increased 3, 9, and 20 times normal in Rai O through II, Rai III through IV, and CLL-aplasia groups, respectively. Removal of T cells from marrow increased growth of CFU-E and BFU-E in all Rai O through IV patients, but the increase was significant in the CLL-aplasia group only (P less than .05). However, autologous coculture of marrow T cells or T gamma cells but not B cells with marrow B + T-depleted null cells at ratios of 0.2:1 to 1:1 suppressed CFU-E and BFU-E growth in all three patient groups. We conclude that the hypoproliferative anemia occurring in the course of B cell CLL is due to gradual accumulation in the marrow of T gamma lymphocytes which suppress erythroid progenitor cell growth. T gamma cell suppression of erythropoiesis and marrow T gamma cell expansion is detectable in the earliest Rai stages of the disease.

Adult↗

PubMed1993

[Experience with the combined diagnosis and therapy of locally advanced carcinoma of the uterine cervix (stage FIGO IIB-III). Transrectal ultrasonography and CT in the staging and in follow-up after therapy. Preliminary results].

The diagnosis, staging, therapy and follow-up of advanced epidermoid cervical carcinoma (FIGO stages IIB-III) have been studied in our university since January 1990. By December 1992, a team of specialists including radiologists, radiotherapists, gynecologists and pathologists divided 54 patients into two random treatment groups: group A patients, after systemic chemotherapy (CDP, 2 cycles) and diagnostic reevaluation, underwent radical surgery; group B patients received conventional radiotherapy alone (ERT 45 Gy+IRT or END-RT 20-25 Gy). All patients were examined by means of transrectal US (TRUS) and CT, after clinical examination under sedation, at staging and during the follow-up. The exams were performed periodically for group B patients and after systemic chemotherapy for group A patients. Imaging findings were compared with pathology only in group A. All imaging results were filed. The results confirm some literature data--e.g., 62% diagnostic accuracy for CT and 69% for TRUS, with higher diagnostic accuracy of the latter to evaluate cervical volume and to diagnose local relapses. As for parametrial involvement, both imaging methods tend to understage the early involvement, but only CT tends to overstage the lesions, especially in irradiated patients, due to fibrosclerosis phenomena. TRUS exhibited 69% accuracy, 70% sensitivity and 69% specificity, versus 61%, 62% and 60%, respectively, for CT; clinical examination under sedation had 58%, 60% and 60%, respectively. Both TRUS and CT are faster than endoscopic methods in evaluating vesical and/or rectal involvement. Lymph node metastases at staging, especially those in lumboaortic locations, proved to be unfavorable prognostic signs, as demonstrated by lumboaortic lymph node relapses in 5 group B patients (only 2 of them presented with lymph node metastases at staging; 3 patients had micronodules near the renal vessels), in spite of good local response after radiotherapy. In conclusion, we would like to point out that our team has had an MR unit at its disposal only recently: since the method is considered as the gold standard of imaging, especially in this kind of lesions, the study is still in progress.

Female↗

PubMed1977

Stages I--III Hodgkin's disease in children: results of staging and treatment.

Fifty-two children with clinical stages I-III Hodgkin's disease were evaluated for disease extent between April 1969 and March 1975. All underwent laparotomy and splenectomy. Two patients with liver involvement were excluded. Thirty of 31 patients with pathologically staged IA-IIA disease have been continuous complete remission after mantle and para-aortic irradiation. There have been no extensions into the untreated pelvis. Fourteen of 15 patients with pathologic stages IIB and IIIB disease show no evidence of relapse after TNI and MOPP. Three of four patients with stage IIIA disease developed nodal relapse after irradiation; all are alive without evidence of disease after re-irradiation (3) and MOPP (2). Thus 45 of 50 patients (90%) have remained continuously free of disease after completion of the planned treatment, and overall 49 of 50 (98%) are alive, without evidence of disease. Such results justify continuation of our staging and treatment philosophy in children with Hodgkin's disease.

Adolescent↗

PubMed1977

New assessment of the prognostic significance of histopathology in Hodgkin's disease for laparotomy-negative stage I and stage II patients.

This paper describes preliminary radiotherapy results in 90 patients with Stage I and II Hodgkin's disease who were evaluated by laparotomy, including splenectomy, and liver and bone marrow biopsies. As a result of selection by laparotomy, the estimated five-year survival rate for these patients was 96%. No statistically significant differences were detected in the disease-free survival for patients with mixed cellularity, nodular sclerosis, and lymphocytic predominance disease. Since only one patient with lymphocytic depletion was in this series, no statement can be made regarding this rare histopathology. Patterns of new disease differed for Stage I and II patients. The major difference was that patients with nodular sclerosing Stage II presentations involving the mediastinum were at considerable risk of developing subsequent disease in the pulmonary parenchyma or the pleura. This finding, together with the demonstration that a histologic diagnosis of mixed cellularity did not carry an inferior prognosis, indicates the need for reassessment of the appropriateness of applying treatment programs based on results of lymphangiographically staged patients to Stage I and II patients evaluated by laparotomy.

Adolescent↗

PubMed2000

Interventions for early stage Hodgkin's disease in children.

BACKGROUND: Hodgkin's Disease is one of the most curable cancers in children, particularly at the early stages. The debate rests now more with retention of high cures and eliminating treatment sequelae. OBJECTIVES: To assess relapse free survival and overall survival rates in children with Stage l-llA Hodgkin's Disease treated with radiotherapy, chemotherapy or a combination of the two treatments. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL, Cancer-CD and the Cochrane Library were searched for randomised controlled trials. Key words included 'Hodgkin's Disease', 'Reed-Sternberg cells' and variations of 'child'. SELECTION CRITERIA: Treatments with a combination of the following therapies; involved field radiotherapy, extended field radiotherapy, anthracycline based chemotherapy regimens, or alkylating chemotherapy agents. Patients included children to 19 years of age. DATA COLLECTION AND ANALYSIS: Seven papers were identified as meeting the selection criteria. Of these four were usable, though one only covered a small section of the paper. It was not possible to combine the outcomes as they covered different treatment regimens and the numbers in one study were inaccurate. MAIN RESULTS: The results comparing IF with EF radiotherapy for children are based on one large multi-centred trial. Although the study is substantial and methodologically rigorous, the evidence for efficacy rests simply on this one trial. The results from the other three studies are not generalizable. The outcomes could not be combined as the studies assessed different treatment regimens. In addition there is little evidence to suggest that the methodological quality, particularly in terms of randomisation and simple arithmetic, is of a sufficiently robust nature in two of the studies. REVIEWER'S CONCLUSIONS: The treatment of Hodgkin's Disease Stage l -llA for children has undergone considerable evolution and development in the previous three decades with the introduction and refinement of combined modality treatments. There is now overall consensus that the prognosis for these patients following a short course of chemotherapy and low dose local radiotherapy is very good with a large percentage achieving long-term survival or relapse free survival. The main issues and problems facing practitioners in the field is the reduction and management of late effects and sequelae of treatment. The evidence for this overall agreement is based on a mass of cohort studies that have influenced changes in practice and significantly improved outcomes. However, apart from the collaborative study looking at radiotherapy alone, there is little evidence from randomised controlled trials to support this consensus.

Antineoplastic Agents↗

PubMed2005

Identification of maternal mRNAs in porcine parthenotes at the 2-cell stage: a comparison with the blastocyst stage.

Successful embryonic development is dependent on the temporal and stage-specific expression of appropriate genes. Currently, information on specific gene expression during early cleavage-stage embryos before zygotic gene activation (ZGA) is limited. In the present study, we compare gene expression between porcine 2-cell and blastocyst stage parthenotes to identify genes that are specifically or predominantly expressed by employing annealing control primer (ACP)-based GeneFishing PCR. Using 60 ACPs, we identified and sequenced nine differentially expressed genes (DEGs). A BLAST search revealed that cloned genes or ESTs (GDI-2, MTMR3, MKLN1, NUP88, ePAD, CIRHIM, UPF3B, ITGA2, and CGI-140) had significant sequence similarities with known genes (78-95%) of other species in the GenBank/EMBL database. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) data disclosed that these genes were regulated upstream in metaphase II (MII) oocyte, 1-cell, and 2-cell stage embryos during early pre-implantation. Similarly, upregulation was observed in MII mouse oocytes and 1-cell stage embryos before ZGA, suggesting that these nine differentially expressed orthologous genes play important roles during early cleavage before ZGA. Further analysis of the differentially expressed genes identified in this report should provide the basis for research on early cleavage and activation of the embryonic genome.

Animals↗

PubMed1996

The in vitro development of mouse embryos beyond the blastocyst stage into the hatching and outgrowth stage using different energy sources.

PURPOSE: The purpose of this study was to investigate the effect of male and female serum supplementation on the in vitro development of mouse embryos beyond the blastocyst stage until the outgrowth stage since the latter may be related to the nidation of the embryo. We also studied the effect of EGF addition on embryo culture and blastocyst outgrowth. METHODS AND RESULTS: The blastocyst and hatching rates of two-cell mouse embryos cultured in Ham's F-10 + BSA, Ham's F-10 + male serum, or Ham's F-10 + female serum were found to be comparable (P > 0.05). The outgrowth rate of hatched blastocysts was significantly increased, though, when they were transferred to 50% male serum compared to either 50% BSA or 50% female serum (P < 0.01 and P < 0.05, respectively). In the last experiment, either 100 or 150 ng/ml EGF was added to the culture medium from the two-cell stage till blastocyst development and the latter were cultured till outgrowth in 50% BSA, male serum, or female serum. For both concentrations of EGF, the outgrowth rate was significantly higher in male serum compared to the other conditions (P < 0.01 and P < 0.05, respectively). The outgrowth rate was also higher when EGF was used compared to plain medium before transferring the blastocysts to either male or female serum (P < 0.01 for both). CONCLUSIONS: We conclude that the development of embryos to the outgrowth stage is significantly enhanced by male serum. The addition of EGF from the two-cell stage also significantly improves the outgrowth success rate for both male and female serum conditions.

Animals↗

PubMed2006

One-stage sigmoid colon resection for perforated sigmoid diverticulitis (Hinchey stages III and IV).

INTRODUCTION: Guidelines for the treatment of complicated sigmoid diverticulitis recommend Hartmann's procedure or anastomosis with protective colostomy for Hinchey stage III diverticulitis and Hartmann's procedure only for Hinchey stage IV diverticulitis. We evaluated the outcome of patients with perforated sigmoid diverticulitis Hinchey III/IV undergoing one-stage colon resection and primary anastomosis without protective colostomy. METHODS: After implementation of a protocol to treat Hinchey III/IV diverticulitis with primary anastomosis without protective ileocolostomy, the patients' data were recorded prospectively between August 2001 and August 2003 and analyzed retrospectively from a computer-related database. RESULTS: Of 41 patients, 34 (81%) underwent one-stage sigmoid resection and primary anastomosis, 3 of 41 patients (7%) underwent primary anatomosis with protective ileostomy, and 5 of 41 patients (12%) had a Hartmann's procedure. The mortality was 11% in patients undergoing primary anastomosis and 60% in patients with Hartmann's procedure. The relative risk of co-morbidity factors for lethal outcome after sigmoid resection was 6.94 for preceding operations, 3.75 for renal failure or renal transplantation, and 3.25 for immunosuppression. CONCLUSIONS: One-stage sigmoid resection and primary anastomosis can be performed safely in nearly 90% of all patients with perforated sigmoid diverticulitis (Hinchey III/IV) by surgeons of different training levels. Patients with immunosuppression, chronic renal failure, liver cirrhosis, or previous organ transplantation or complex cardiovascular reconstructive procedures have a significantly increased risk of dying after sigmoid resection for perforated diverticulitis.

Anastomosis, Surgical↗

PubMed1982

Regional myocardial blood flow and ventricular arrhythmias following one-stage and two-stage coronary artery occlusion in anesthetized dogs.

Experiments were performed in 29 anesthetized dogs to compare effects of one-stage and two-stage coronary artery occlusion on ventricular arrhythmias and regional myocardial blood flow (MBF). Two periods of arrhythmias were observed and both were associated with evidence suggesting reentry; i.e., activity in ischemic zone electrograms which bridged the diastolic intervals preceding ventricular ectopic beats. Early ventricular arrhythmias followed progressive deterioration of conduction in the ischemic zone, whereas later arrhythmias occurred unexpectedly with the sudden appearance of bridging activity. One-stage occlusion produced a higher incidence of ventricular arrhythmias and ventricular fibrillation than two-stage occlusion. However, there was no difference in central ischemic zone blood flow, indicating that the protective effect of two-stage occlusion was not due to greater blood flow in this region. There results suggest that factors other than the degree of MBF reduction are important determinants of the incidence and severity of ventricular arrhythmias following coronary artery occlusion.

Anesthesia, General↗

PubMed1991

Surgical template impression during stage I surgery for fabrication of a provisional restoration to be placed at stage II surgery.

The fixture impression method presented permits the construction of a master cast after stage I surgery, enabling the dentist and dental technician to make a provisional crown before stage II surgery. At stage II surgery the surgeon can place the provisional crown instead of a classic abutment or healing cylinder. This eliminates the need for the patient to visit the restorative dentist immediately after stage II surgery for the making of a provisional crown, which can be a scheduling and logistic problem. In addition, better soft tissue contour is possible at stage II surgery, as the premade provisional crown can be shaped to the desired dimensions in the laboratory for ideal esthetics. The soft tissue will adapt to the predetermined surface dimensions during initial healing. Ideal soft tissue contours are present and stable when the final impression is made, which enables better esthetics to be developed for the permanent fixture-retained single-tooth restoration.

Acrylic Resins↗

PubMed2005

A novel oligodendrocyte cell line OLP6 shows the successive stages of oligodendrocyte development: late progenitor, immature and mature stages.

The successive stages of development from oligodendrocyte progenitor to mature oligodendrocyte have been investigated in detail by using stage-specific antibodies. However, no cell lines are available that show stepwise differentiation from oligodendrocyte progenitors to mature oligodendrocytes. Here we show the establishment of an immortalized oligodendrocyte cell line, OLP6, from adult transgenic rats harboring the temperature-sensitive simian virus 40 large T-antigen gene. The OLP6 cells had a fibroblastic morphology and continuously proliferated at 33 degrees C. They displayed growth arrest and multipolar morphology when they were cultured at 39 degrees C. They express the oligodendrocytic markers O4, 2'-3'-cyclic-nucleotide 3'-phosphodiesterase, galactocerebroside and second endothelial differentiation gene receptor-2 at 39 degrees C. The OLP6 cells underwent apoptosis upon serum withdrawal at 39 degrees C. Lysophosphatidic acid inhibited this apoptosis and promoted the expression of myelin basic protein. These results demonstrate that the activation of endothelial differentiation gene receptor-2 exerts anti-apoptosis and myelinogenesis effects on the OLP6 cells. Taken together, the OLP6 cells in the late oligodendrocyte progenitor stage can progress to the immature oligodendrocyte stage by shifting culture temperature. Furthermore, lysophosphatidic acid promoted the maturation of OLP6 cells in the immature oligodendrocyte stage. Such OLP6 cells should provide a potent model system for studying the precise mechanism involved in stepwise differentiation of oligodendrocytes.

Animals↗

PubMed1999

Expression of cytotoxic proteins by neoplastic T cells in mycosis fungoides increases with progression from plaque stage to tumor stage disease.

Granzyme B (GrB) and T-cell-restricted intracellular antigen (TIA-1) are cytotoxic proteins that are specifically expressed by cytotoxic CD4 or CD8 positive T cells and natural killer cells. Recent studies demonstrated frequent expression of GrB and TIA-1 by neoplastic cells in primary cutaneous CD30(+) large T-cell lymphomas and lymphomatoid papulosis but not in CD30(-) large T-cell lymphomas. In the present study, 74 biopsies from 54 patients with mycosis fungoides (MF) were investigated for the expression of GrB and TIA-1 using immunohistochemistry on paraffin sections. Staining of more than 10% of the neoplastic T cells for GrB or TIA-1 was considered positive. All but two follow-up biopsies had been obtained from patients without extracutaneous disease at the time of biopsy. Expression of TIA-1 and GrB was found in 33 (45%) and 14 (19%) of 74 MF biopsies, respectively. Comparison of biopsies from T3NoMo-stage MF (n = 27) and T2NoMo-stage MF (n = 45) showed increased expression of TIA-1 (55 versus 37%) and GrB (33 versus 9%) in T3NoMo-stage MF. Evaluation of multiple sequential biopsies from successive stages of MF also revealed an increase in the GrB/TIA-1 expression with tumor progression in five of eight cases. A clearcut relation between the expression of TIA-1 and/or GrB and the type of skin lesion biopsied was found. Considering all 74 biopsies, expression of TIA-1 and GrB was found in 18 of 50 (35%) and 5 of 50 (10%) patches or plaques, 9 of 16 (55%) and 3 of 16 (20%) tumors without blastic transformation, and 6 of 8 (75%) and 6 of 8 (75%) tumors with blastic transformation (defined as >50% blast cells). Correlation between GrB/TIA-1 expression in first diagnostic biopsies from patches or plaques from 40 patients with T2NoMo-stage MF and clinical follow-up data did not reveal differences in clinical behavior and survival between patients with (n = 14) or without (n = 26) expression of cytotoxic proteins, indicating that MF expressing cytotoxic proteins should not be considered as a separate group.

Antigens, CD↗

PubMed1998

The selective use of a single-stage and a two-stage technique for hypospadias correction in 157 consecutive cases with the aim of normal appearance and function.

This paper establishes the aim of normal function and appearance in hypospadias surgery. In order to meet this aim we have used a combination of a single-stage and a two-stage repair, both incorporating foreskin reconstruction. The technique of single-stage repair is illustrated using operative photographs. Our experience with 157 repairs in a 3-year period is described. Thirty-five single-stage repairs were completed with no complications; 122 two-stage repairs were carried out, in which a 5% fistula rate was achieved in primary cases. Salvage reconstruction had a higher incidence of complications.

Aged↗

PubMed1997

One-stage midline unifocalization and complete repair in infancy versus multiple-stage unifocalization followed by repair for complex heart disease with major aortopulmonary collaterals.

BACKGROUND: Patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries have traditionally required multiple unifocalization staging operations before undergoing complete repair. Recently, the feasibility of a single-stage unifocalization and repair was demonstrated by Hanley. In this report, we describe our experience with each approach. METHODS AND RESULTS: Since 1989, 11 of 12 patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries have undergone complete surgical correction. The first seven patients were subjected to staged bilateral unifocalizations, with repair being achieved in six (group I). The last five patients have undergone a single-stage midline unifocalization and repair via a sternotomy (group II). Four of these were infants (2 weeks to 9 months) and one was 13 years old. All patients in group I had tetralogy of Fallot, whereas in group II three patients had tetralogy of Fallot, one patient had double-outlet right ventricle, and one patient had complete atrioventricular canal and transposition. In group I, the median age at the first operation was 43 weeks. Complete repair was performed at a median age of 3.5 years, with a mean number of 3.3 operations required. In group II, only one operation was required to achieve complete repair at a median age of 28 weeks. The postoperative right ventricular/left ventricular pressure ratio was 0.49 in group I and 0.45 in group II. One intraoperative death and one late death occurred in group I and no early or late deaths in group II. Currently, four patients in group I and all five patients in group II are alive and well. CONCLUSIONS: Early intervention with both surgical approaches can lead to complete biventricular repair in most patients. Because the single-stage midline unifocalization and repair can achieve a completely repaired heart in infancy with one operation, it is currently our approach of choice.

Aorta, Thoracic↗

PubMed1994

Laparoscopic single stage and staged orchiopexy.

The initial series of laparoscopic single stage orchiopexy for the abdominal or emergent impalpable undescended testis is reported. The first laparoscopic orchiopexy was performed at our institution in October 1991. Between October 1991 and January 1993, 14 patients (16 testes) underwent minimally invasive surgery with 6 months of followup in all cases. No evidence of testicular loss or acute atrophy has occurred, with the entire procedure being accomplished by laparo-endoscopic techniques in all cases. Treatment of 3 of the 16 testicles consisted of stage 2 of staged orchiopexy, and to our knowledge these cases represent the first stage 2 orchiopexy completed by laparoscopic techniques. In those cases stage 1 was performed by laparoscopic clipping of the vessels. The details of the procedure as we now perform it are described.

Adolescent↗

PubMed1998

Tailored interventions to communicate stage-matched information to smokers in different motivational stages.

Smokers in stages of low readiness to quit (immotives and precontemplators) and smokers in stages of high readiness to quit (contemplators and preparers) were randomly allocated to 1 of 4 tailored intervention conditions offering outcome information, self-efficacy-enhancing information, both sorts of information, or no information. Data on 1,540 smokers, stratified by stage, were analyzed. The primary outcome measure was stage transition. The hypotheses with regard to stage-matched information for immotives and precontemplators were not verified. With regard to contemplators and preparers, the following was found: Compared with the control group, contemplators benefited the most from both sorts of information, whereas preparers benefited the most from self-efficacy-enhancing information only. Comparisons between contemplators and preparers who were assigned to the matched treatment and contemplators and preparers who were assigned to the mismatched treatment supported these findings.

Adult↗

PubMed1989

Visual discrimination by cats given lesions of visual cortex in one or two stages in infancy or in one stage in adulthood.

Sparing of visual function was studied in cats with bilateral cortical damage to Areas 17 and 18 and most of Area 19. Cats with lesions made in 2 stages, on Postnatal (P) Days 3 and 6, in 1 stage on P6, or in 1 stage in adulthood were compared with sham-operated controls on 10 visual discrimination tasks. On some tasks, both groups of cats that underwent surgery as infants showed considerable sparing of function compared with cats that had surgery as adults; the latter group showed a marked impairment. However, on several of the discriminations, 2-stage lesions permitted almost total sparing of pattern vision, whereas 1-stage lesions made neonatally were almost as debilitating as those incurred in adulthood. The findings suggest that differential behavioral consequences can follow physiological or anatomical changes, or both, that occur within a 4-day neonatal interoperative period.

Aging↗

PubMed1985

Mouse major histocompatibility class I gene expression begins at midsomite stage and is inducible in earlier-stage embryos by interferon.

To determine the timing of major histocompatibility complex class I gene expression during embryonic development, binding of anti-class I antibodies and appearance of class I gene transcripts were examined in mouse embryos from the egg-cylinder stage through day 16 of gestation. By using two series of monoclonal antibodies reactive with monomorphic and polymorphic determinants of class I antigens, it was found that cell-surface expression of the antigens becomes detectable at a low level only after midsomite stage on gestation day 10, at a time when embryos are developed beyond primordial organogenesis and have partial blood circulation. In agreement with the above finding, a low level of class I mRNA became detectable in day 9 and older embryos in blot hybridization. The level of class I transcripts in embryos at least to day 13 remained less than 1/50th that in adult spleen cells. Cells from head-fold stage embryos (gestation day 8), which otherwise do not have an appreciable amount of class I mRNA or surface antigens, begin to express a high level of antigens upon treatment with mouse alpha/beta or gamma interferon. This induction of class I antigen expression appears to be stage specific in that embryos in an earlier egg-cylinder stage (day 6) failed to express the antigens after interferon treatment. A possible role of interferons in activating class I genes during in vivo embryonic development is suggested.

Animals↗