Consolidation of first-line therapy with busulphan and melphalan, and autologous stem cell rescue in children with Ewing's sarcoma.

According to the published report on current practice of hematopoietic SCT in Europe, high-dose therapy (HDT) with autologous stem cell support is a standard of care in paediatric patients with high risk (HR) or relapsed Ewing's sarcoma (ES). Randomized trials, however, have not confirmed the value of this procedure yet. In this retrospective analysis we intended to evaluate the role of HDT as a consolidation therapy in first remission of ES. A total of 102 patients were included in the analysis and divided according to the following risk factors: metastatic disease at presentation, feasibility of surgery and histological response after induction. Forty-one patients were classified as standard risk (SR) patients, while the remaining 61 children, with at least one risk factor, were classified as HR patients. HR group patients were non-randomized and qualified according to the decision of the local clinician to give a conventional consolidation (CC) or to perform high-dose chemotherapy and radiotherapy in selected patients. Twenty-six children were given CC while 35 patients were treated with HDT. The HDT consisted of oral BU 4 mg/kg p.o. in divided doses daily for 4 days (total dose 16 mg/kg) followed by melphalan 140 mg/m(2) i.v. on day -2. Probability of relapse-free survival (RFS) in median observation time was significantly worse in HR patients who were given CC therapy as compared with children with HR features receiving high-dose chemotherapy (0.27 vs 0.66 (P = 0.008); OS 0.31 vs 0.71 (P = 0.007), respectively). Patients from the SR group had a probability of RFS of 0.72 and OS of 0.75, and the difference between SR and HR patients after HDT was NS (P = 0.37). Our observation confirms that the consolidation of the first-line treatment with BU and melphalan improves the outcome in ES patients with HR features.

Neurologic complications in children after hemaopoietic stem cell transplantation: a single-center experience.

UNLABELLED: Neurologic complications may occur in patients undergoing haematopoietic stem cell transplantation (HSCT). The aim of the study was to evaluate the frequency and type of neurologic complications in children after HSCT. We performed a retrospective analysis of the incidence and outcome of neurologic complications among 171 consecutive children transplanted in one center. RESULTS: Among 84 autologous and 87 allogeneic (47 matched sibling donors, 31 matched unrelated donors, 8 mismatched family donors, and 1 cord blood) transplants, 7 patients (4%) developed neurologic complications, all of whom had undergone allogeneic transplantation (7/87 = 8%). These patients had relapses of acute leukemia (n = 3; acute myeloblastic in two and acute lymphoblastic in one), chronic leukemia, (n = 1), myelodysplastic syndrome (n = 2), and adrenoleudystrophy X (n = 1). Neurologic complications occurred after a median follow-up of 1 month (range, 14 days to 19 months). Of seven patients, four died. Neurologic complications were the cause in two patients. CONCLUSIONS: Among the analyzed material the risk of neurologic complications was lower than in other studies and these events were observed only in children undergoing allogeneic transplantation.

Our experiences in total condylar knee replacement.

The purpose of this study was to evaluate the outcomes of total knee replacement using endoprostheses. The material consisted of 78 knee endoprostheses in 68 patients operated in our Clinic over a 3-and-a-half-year period beginning in March 1995. Outcome assessment was based on clinical and radiological examinations before and after surgery, with due regard for the patient's subjective evaluation. The average follow-up period was 13 months. The majority of the patients were found to have improved walk efficiency, eliminated or reduced pain, improved mobility, corrected limb axis, and excellent subjective evaluation.

Bone marrow transplantation does not ameliorate the neurologic symptoms in mice deficient in hypoxanthine guanine phosphoribosyl transferase (HPRT).

The use of bone marrow transplantation (BMT) for the treatment of genetic diseases with neurologic involvement has yielded mixed results. We have employed a mouse model of Lesch-Nyhan disease (LND) to assess the efficacy of BMT in ameliorating the neurologic manifestations of the disease. Adult HPRT-deficient mice exhibit a measurable decrease in striatal dopamine levels and a hypersensitivity to amphetamine. Marrow-ablated adult HPRT-deficient mice were transplanted with marrow from congenic HPRT-expressing mice. BMT altered neither the neurochemical nor the behavioral phenotypes in either HPRT-positive or HPRT-deficient mice. Barring any important species differences, these results suggest that BMT in its present form may not be an effective therapy for Lesch-Nyhan syndrome.

[Arthroscopic treatment for synovial chondromatosis of the shoulder--case report]. / Artroskopowe leczenie chrzestniakowatosci maziówkowej stawu ramiennego--opis przypadku.

A case of 15 years old schoolgirl with synovial chondromatosis of the right shoulder is presented. The diagnosis has been confirmed by MRI. At arthroscopy approximately 70 oval loose bodies 5-8 mm in size have been removed. Postoperatively, no complication occurred. The case presented demonstrates advantage of arthroscopic treatment of this rare condition.

Breast carcinoma survival analysis for African American and white women in an equal-access health care system.

BACKGROUND: This retrospective review of breast carcinoma cases in the Department of Defense (DoD) Central Tumor Registry evaluated differences in survival patterns between African American and white women treated in U.S. military health care facilities. The study examined the effects of age, stage of cancer, tumor size, grade, lymph node involvement, waiting time between diagnosis and first treatment, marital status, military dependent status, alcohol usage, tobacco usage, and family history of cancer. METHODS: Researchers reviewed the tumor registry records of 6577 women (5879 whites and 698 African Americans) diagnosed with breast carcinoma. The patients, ages 19-97 years, were diagnosed between 1975 and 1994. A hazard ratio (relative risk of mortality) model compared African American and white patients, adjusting for various combinations of covariates; impact of independent variables on the risk of death; prognostic factors significantly associated with survival; disease free and overall survival times; effects of ethnicity, stage, and age on survival; and trends in stage at diagnosis. A P value (2-sided) of less than 0.05 was considered statistically significant. RESULTS: After adjustment for age, the risk of death was 1.45 (95% confidence interval [CI], 1.20-1.76) times greater for African American women than for white women. Adjustment for stage reduced the risk to 1.41 (95% CI, 1.16-1.70); further adjustment for demographic variables and most clinical variables had no effect. Still, African American women treated in the military health care facilities had a better survival rate than African American women represented in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. In our study, the 5-year risk of death, from any cause, was 1.37 for African American women with breast carcinoma; in other words, the mortality rate for African American women was 24.77% compared with 18.08% for white women. In the latest SEER data, the 5-year relative risk of death for African American women compared with white women is 1.86. The mortality rate in SEER is 34.2% for African American women and 18.4% for white women. The survival rate for white DoD beneficiaries is comparable to that for white women in SEER. CONCLUSIONS: These observations suggest that ready access to medical facilities and the full complement of treatment options that are standard for all DoD patients improve survival rates for African American women. However, a significant unexplained difference in survival still exists between African American and white military beneficiaries.

Vasopressin gene expression in rat choroid plexus.

Vasopressin (VP) levels in cerebrospinal fluid (CSF) change in response to physiological stimuli and under various pathological conditions. The sources of CSF VP have yet to be clarified, however. In the present study, we provide evidence indicating that VP is synthesized in the choroid plexus, the primary site of CSF formation. All experiments were performed on adult male Sprague-Dawley rats. The presence of VP mRNA in choroid plexus epithelium was demonstrated by in situ hybridization histochemistry using the 35S-labeled riboprobe that was complementary to cDNA fragment of rat VP encoding the C-terminus part of proVP. In situ hybridization findings were confirmed by reverse transcriptase-polymerase chain reaction analysis. Immunohistochemistry for VP-associated neurophysin (VP-NP), a polypeptide component of proVP, revealed subapical accumulation of VP-NP-immunopositive product in choroidal epithelial cells. Immunoprecipitation and immunoblotting of choroidal protein extracts with anti-VP-NP antibody demonstrated the presence of a approximately 10-kD polypeptide that was also detected in hypothalamus. We hypothesize that the choroid plexus-derived VP exerts autocrine and/or paracrine effects on tissues near the CSF system.

[Mikrozespol fixator in treatment of metacarpal malunion (preliminary report)]. / Stabilizator Mikrozespol w leczeniu powiklan zrostu kosci sródrecza (doniesienie wstepne).

Results of surgical treatment in 6 patients aged 21-40 (mean 30 years) with metacarpal malunion are presented. External version of Mikrozespol fixator has been used for stabilization of the fragments. Excellent radiographic result has been achieved in all cases. Functional assessment revealed 5 excellent and 1 good result. Bony union occurred after 7 weeks; complete function returned 5 weeks after surgery. The authors conclude, that Mikrozespol stabilization constitutes an alternative method for carpal malunion treatment.

A long-term study of the efficacy of treatment of localized prostate cancer.

This paper presents a retrospective comparison of patients undergoing treatment for clinically localized prostate cancer. We reviewed the age, grade, and stage at diagnosis as well as the survival and recurrence rates of 222 patients treated for carcinoma of the prostate with either radical prostatectomy (RP) or radiotherapy (XRT) at four Army medical centers. Mean follow-up was 8.02 years (range 0.026-32.5 years). Stage and grade were similar in patients receiving either RP or XRT. Kaplan-Meier estimates showed that patients who underwent RP had a significantly greater disease-specific survival (p = 0.0001) and a significantly lower rate of distant metastases (p = 0.006) than did those who received XRT. There was no significant difference in the rate of local progression (p = 0.276) or in the mean time to local progression (XRT = 3.5, RP = 4.0 years) or to distant metastases (XRT = 3.79, RP = 4.52 years). Cox proportional hazards model incorporating age, stage, grade, and treatment type demonstrated that those patients who received XRT had more than two times the risk of dying of their disease than did those who underwent RP (risk ratio = 2.37; 95% confidence interval = 1.49-3.76). These data in similar groups of patients suggest that metastasis-free survival is improved in those who receive RP compared with XRT and that this translates into an enhanced survival advantage. Further study of larger groups of patients stratified by risk factors in randomized, prospective trials with longer follow-up will improve our ability to determine the best treatment for clinically localized prostate cancer.

Effect of various types of exercise training on 5'-nucleotidase and adenosine deaminase activities in rat heart: influence of a single bout of endurance exercise.

The aim of the present study was to find out whether activities of the enzymes controlling adenosine metabolism, 5'-nucleotidase (5NT) and adenosine deaminase (ADA), in the left ventricle of the rat's heart change after 6 weeks of endurance or sprint training. Additionally, an influence of a single bout of endurance exercise till exhaustion on activities of these enzymes was investigated in sedentary and trained rats. The rats were divided into three groups: (1) sedentary controls (C), (2) endurance-trained (ET), and (3) sprint-trained (ST). It was shown that both types of training increased 5NT, but did not change ADA activity in the rat heart. Acute exercise till exhaustion did not affect 5NT activity in the heart taken from C and ST rats, but decreased its activity in the ET group. The heart ADA activity after exhaustive exercise increased in C and in ET group, but decreased in ST animals. It is concluded that physical training affects cardiac adenosine metabolism and the type of training may exert an influence on purine nucleotides metabolism in the heart during exhaustive exercise.

5'-Nucleotidase and adenosine deaminase activities in hypertrophied rat heart. The effect of tachycardia.

Activity of 5'-nucleotidase (5NT) and adenosine deaminase (ADA) in the left heart ventricle was examined at normal heart rate and after atrial pacing in six weeks after constriction of the aorta above or below the renal vessels and in sham operated rats. The aorta constriction above the vessels reduced activity of 5NT by 29% and increased activity of ADA by 33%, whereas the constriction below the vessels resulted in elevated activity of both enzymes: 5NT by 16% and ADA by 145% at normal heart rate. The atrial pacing reduced 5NT activity and did not affect ADA activity in control rats and in those with constriction of the aorta below the vessels. The activity of both enzymes increased after constriction of the aorta above the renal vessels. It is concluded that adenosine metabolism in the hypertrophied heart may be changed due to changes in its production and degradation. Renin-angiotensin-aldosterone system seems to be involved in regulation of the activities of adenosine metabolizing enzymes in the hypertrophied heart.

Race, treatment, and long-term survival from prostate cancer in an equal-access medical care delivery system.

OBJECTIVE: To evaluate long-term survival of black and white prostate cancer patients in an equal-access medical care system to help distinguish biological from medical and social explanations of mortality differences. DESIGN AND SETTING: Retrospective study of US Department of Defense tumor registry patients with prostate cancer. Ethnicity, age, diagnosis, staging, risk factors, treatment, and survival end points were extracted. PATIENTS: Prostate cancer patients (N = 1606; 7.5% black, 92.5% white) who were active-duty personnel, dependents, or retirees eligible for care in the military medical system. MAIN OUTCOME MEASURES: Racial differences in tumor stage and grade, risk factors, recurrence, and treatment wait time (time between initial diagnosis and initial treatment); influence of stage, grade, treatment, wait time, age, and race on survival. RESULTS: No differences were found in behavioral risk factors or tumor grade or size, but blacks entered active treatment (P < .001) and exhibited a higher relative risk of cancer (P = .01) in younger age groups, presented with higher stage (P < .001), and demonstrated increased progression in distant metastatic disease (P = .01). No significant differences were detected in overall wait time. When adjusted for stage, no difference was found in type of treatment. Overall, stage, grade, and age were found to affect survival (P = .04 to P < .001), but race did not. When analyzed by stage, blacks demonstrated a clear trend of longer survival for distant metastatic disease (P = .04 to P = .06). This trend was confirmed using Kaplan-Meier estimates (P = .04, likelihood ratio). CONCLUSIONS: This analysis suggests that in an equal-access medical care system there are no stage-specific differences in treatment between black and white prostate cancer patients. Survival among blacks is similar to that among whites and may surpass it for high-stage disease.

Morbidity and mortality following radical prostatectomy: a national analysis of Civilian Health and Medical Program of the Uniformed Services beneficiaries.

Recent evidence from an analysis of Medicare patients undergoing radical prostatectomy has suggested that perioperative mortality may be substantially greater than that reported in institutional series. To estimate the perioperative mortality and survival of patients of a younger and potentially more representative population of the United States, Civilian Health and Medical Program of the Uniformed Services institutional claims data from October 1, 1987 to January 1, 1993 were analyzed. A total of 1,059 subjects was examined of an average of 60.0 years and all were younger than 65 years. Using Kaplan-Meier estimates, mortality rates following surgery were calculated to be 0.28% at 30 days, 0.28% at 90 days, 1.02% at 1 year, 1.95% at 2 years, 3.14% at 3 years and 4.64% at 4 years. Observed 1 to 5 mortality rates in this series ranged from 0.362 to 0.487 of the expected mortality when compared to the general population and they were statistically significant. At 30 and 90 days postoperatively 3.1% and 4.6% of the patients were rehospitalized. Data demonstrated that mortality and morbidity from radical prostatectomy were low and that conclusions drawn on outcomes of treatment for carcinoma of the prostate should focus on the entire age range of patients who undergo this procedure in the United States.

Analysis of the p53 gene and its expression in human glioblastoma cells.

Chromosome 17p has been shown to be an early and frequent target for loss of heterozygosity through mitotic recombination in astrocytomas. These losses are frequently accompanied by point mutations in the p53 gene of the remaining allele, resulting in loss of wild type p53 function. However, a fraction of astrocytomas retain constitutional heterozygosity and do not have p53 mutations; some of these lose wild type p53 activity through binding to the protein product of amplified mdm2 genes. To test whether loss of wild type p53 biological function is a necessary step in astrocytoma progression we analyzed p53 expression and biological function in 13 glioma cell lines. All the cell lines expressed a 2.8-kilobase p53 transcript and showed various amounts of p53 protein by immunoprecipitation, except for cell line LN-Z308 which had only a small truncated p53 mRNA and no protein expression. To test whether the p53 expressed in these cell lines was functionally wild type or mutant we transfected them with a plasmid construct harboring a chloramphenicol acetyltransferase (CAT) reporter gene under the control of transcriptional elements that are induced by wild type but not mutant p53. Four lines were shown to retain wild type p53 function. Sequencing of the p53 gene in two of these cell lines confirmed the wild type genotype. These results show that inactivation of the p53 gene is not an obligatory step in glioblastoma genesis. This suggests either that two pathways (p53 inactivation dependent or independent) may lead to a tumor group classified histologically as glioblastoma or that in some cases p53 mutations are bypassed due to the presence of mutations in downstream effector genes.

Catecholaminergic neurons result from intracerebral implantation of embryonal carcinoma cells.

A replication-defective retrovirus was used to introduce the marker gene nlsLacZ into the murine embryonal carcinoma (EC) cell line PCC7-S-aza-R-1009. Undifferentiated EC cells were implanted into the central nervous system of adult rats. One month later, the grafted cells continued to express the nlsLacZ gene. Immunohistochemical analysis demonstrated the presence of EC-derived neurons. These neurons were capable of expressing tyrosine hydroxylase and extended neurites into the host parenchyma. EC-derived glial cells could not be detected. There was no evidence of tumorigenicity. These results demonstrate the utility of EC cells for introduction of exogenous gene products into the central nervous system in experimental models of gene therapy.

Temperature-sensitive DNA mutant of Chinese hamster ovary cells with a thermolabile ribonucleotide reductase activity.

JB3-B is a Chinese hamster ovary cell mutant previously shown to be temperature sensitive for DNA replication (J. J. Dermody, B. E. Wojcik, H. Du, and H. L. Ozer, Mol. Cell. Biol. 6:4594-4601, 1986). It was chosen for detailed study because of its novel property of inhibiting both polyomavirus and adenovirus DNA synthesis in a temperature-dependent manner. Pulse-labeling studies demonstrated a defect in the rate of adenovirus DNA synthesis. Measurement of deoxyribonucleoside triphosphate (dNTP) pools as a function of time after shift of uninfected cultures from 33 to 39 degrees C revealed that all four dNTP pools declined at similar rates in extracts prepared either from whole cells or from rapidly isolated nuclei. Ribonucleoside triphosphate pools were unaffected by a temperature shift, ruling out the possibility that the mutation affects nucleoside diphosphokinase. However, ribonucleotide reductase activity, as measured in extracts, declined after cell cultures underwent a temperature shift, in parallel with the decline in dNTP pool sizes. Moreover, the activity of cell extracts was thermolabile in vitro, consistent with the model that the JB3-B mutation affects the structural gene for one of the ribonucleotide reductase subunits. The kinetics of dNTP pool size changes after temperature shift are quite distinct from those reported after inhibition of ribonucleotide reductase with hydroxyurea. An indirect effect on ribonucleotide reductase activity in JB3-B has not been excluded since human sequences other than those encoding the enzyme subunits can correct the temperature-sensitive growth defect in the mutant.

Effects of forskolin on the longitudinal internal resistance (ri) in rabbit sinus node strips.

The effect of several concentrations of 7-0-hemisuccinyl, 7-deacetyl forskolin on ri was studied by means of microelectrode and single sucrose gap techniques. Twenty mumol.l-1 of forskolin added to the sucrose gap lowered ri by 15% below the control value. The drug applied at 50 mumol.l-1 initially decreased ri by 31%, and then it increased the resistance by 43% above the control value. The possible mechanisms underlying these effects are discussed in terms of cAMP and Ca action on the cell coupling.

Effects of cyclic nucleotides on the longitudinal internal resistance in the rabbit sinus node.

The effect of dibutyryl cyclic AMP as well as dibutyryl cyclic GMP on the longitudinal internal resistance was studied in the rabbit sinus node strips by means of microelectrode and sucrose gap techniques. Dibutyryl cyclic AMP added to the sucrose gap decreased the resistance and increased the spontaneous rate whereas dibutyryl cyclic GMP evoked the opposite effects. These results suggest that cyclic nucleotides influence the cell coupling in the sinus node.