Marrow-ablative chemotherapy followed by tandem autologous hematopoietic cell transplantation in pediatric patients with malignant brain tumors.

To improve survival in young children with malignant brain tumors, irradiation-avoiding or -minimizing marrow-ablative chemotherapy (HDCx) with autologous hematopoietic cell transplantation (AuHCT) has been investigated. We evaluated the outcome of 44 children with malignant brain tumors treated with HDCx and tandem AuHCT at Children's Hospital Los Angeles between June 1999 and July 2012. Forty-four children with malignant brain tumors were studied. Twenty-one had medulloblastoma/primitive neuro-ectodermal tumor, eight atypical teratoid/rhabdoid tumor (ATRT), five high-grade glioma, four malignant germ cell tumor, three ependymoma and three choroid plexus carcinoma. Twenty-nine patients received three tandem transplants and 15 received two tandem transplants, respectively. The 5-year PFS and overall survivals (OS) for all patients were 46.3±8.2% and 51.7±8.5%, respectively. The PFS and OS for 27 newly diagnosed patients were 68.9±9.9% and 73.5±9.3%, respectively, compared with 17 transplanted at relapse 11.8±9.8% (P<0.001) and 15.1±12.3% (P=0.0231), respectively. The 5-year PFS and OS in 13 previously unirradiated patients were 74±13% and 74±13% versus 33.2±9.8% and 40.2±10.6% in 31 irradiated patients (P=0.11 and P=0.239), respectively. One patient died of transplant-related toxicity. HDCx with tandem AuHCT is feasible and safe in children with malignant brain tumors with encouraging irradiation-free survival in newly diagnosed children.

Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the 'Head Start' trials, 1991-2009.

Since 1991, three sequential prospective clinical trials have been conducted by the 'Head Start' (HS) Consortium in which young children with newly-diagnosed malignant central nervous system (CNS) tumors were treated with induction chemotherapy followed by single-cycle marrow-ablative chemotherapy and autologous hematopoietic rescue as a means of improving disease cure rate and quality of survival through avoidance (<6 years old at diagnosis) or reduction (6-10 years old) of brain irradiation. Bone Marrow (HS I) or filgrastim-mobilized peripheral hematopoietic cells (HS II and III) were obtained following recovery from the first and/or second induction cycles. Radiotherapy was administered following all chemotherapy only for patients with residual tumor following completion of induction or with age greater than 6 years at diagnosis. Two hundred and twenty-six children were enrolled on three consecutive HS trials with primary malignant CNS tumors and underwent marrow-ablative chemotherapy. The 100-day treatment-related mortality (TRM) steadily declined as did grade IV transplant-related oropharyngeal mucositis. Factors most likely associated with the decrease in TRM and morbidity are increasing experience with the marrow-ablative chemotherapy regimen combined with improved leukapheresis and post-reinfusion supportive care techniques, contributing toward improved overall survival.

Apparent diffusion and fractional anisotropy of diffuse intrinsic brain stem gliomas.

BACKGROUND AND PURPOSE: DIBSGs have the worst prognosis among pediatric brain tumors with no improvement of outcome for several decades. In this study, we determined whether diffusion imaging could improve patient stratification and our understanding of the impact of therapies. MATERIALS AND METHODS: Nine baseline and 24 follow-up DTI studies performed in 9 patients on a 1.5T clinical MR imaging scanner were reviewed. ADC and FA were measured for the whole lesion and at 5 anatomic levels: the rostral medulla, caudal pons, midpons, rostral pons, and caudal midbrain. Reference data were obtained from 8 controls with normal brain stem, 6 patients with medulloblastoma, and 7 patients with pilocytic astrocytoma. RESULTS: ADC was higher in untreated DIBSG than in normal brain stem and medulloblastoma (1.14 ± 0.18 [×10⁻³ mm²/s] versus 0.75 ± 0.06 and 0.56 ± 0.05, both P < .001). FA was lower in DIBSG than in normal brain stem (0.24 ± 0.04 versus 0.43 ± 0.02, P < .001) but was higher than that in pilocytic astrocytoma (0.17 ± 0.05, P < .05). Lower baseline ADC and higher FA correlated with a worse clinical course. Correlations were more significant at the caudal midbrain than in other regions. ADC decreased and FA increased after RT. Changes of FA after RT at the caudal midbrain correlated with event-free survival. CONCLUSIONS: Baseline ADC and FA of DIBSG revealed hypocellular tumors with extensive edema. Diffusion changes after therapy implied reduced edema but did not support a significant response to therapy. The significance of diffusion properties varied with anatomic locations, the caudal midbrain being particularly important.

Central nervous system (CNS) tumors in the first six months of life: the Children's Hospital Los Angeles experience, 1979-2005.

BACKGROUND: The authors report the experience at the Children's Hospital Los Angeles with brain tumors diagnosed before 6 months of age, describing the characteristics of the patients, their tumors, treatment strategies, and prognostic factors. METHODS: Thirty-three children who were identified between 1979 and 2005 were included. Twelve were female (36%). There were 11 gliomas, 9 choroid plexus tumors, 8 medulloblastomas and supratentorial primitive neuroectodermal tumors (PNET), 2 atypical teratoid/rhabdoid tumors (ATRT), and 1 each of ependymoma, craniopharyngioma, and immature teratoma. Locations of primary tumors included 21 supratentorial (64%) and 7 posterior fossa, and 5 tumors involved both compartments. The treatment strategies included 5 patients with biopsy only, 18 less than gross total resections (

Pattern of cervical dilatation in previous lower segment caesarean section patients.

The pattern of cervical dilatation during labour in 100 patients with previous lower segment caesarean section (LSCS) was determined in a prospective partographic study. Eighty-four subjects delivered successfully by vaginal route. The mean initial dilatation rate (IDR) and average dilatation rate (ADR) were 0.884 cm/hour and 1.255 cm/hour respectively. The mean IDR and ADR of the patients who delivered vaginally were 0.96 cm/hour and 1.41 cm/hour respectively, while of those who required repeat LSCS mean IDR was 0.44 cm/hour and mean ADR was 0.42 cm/hour. Hence ADR in cases who required repeat LSCS was significantly slower as compared to those who delivered vaginally (p < 0.01). Most (87.5%) of the cases who required repeat LSCS crossed the alert line as compared to 34.5% of patients who delivered vaginally. The mean admission delivery interval (ADI) was 9.45 +/- 4.29 hours in patients with no previous vaginal delivery and 8.02 +/- 4.83 hours in patients with previous vaginal delivery. The mean durations of 1st and 2nd stages of labour were 11.8 +/- 5.35 hours and 29.4 +/- 27.3 minutes respectively. It is concluded that partographic evaluation is an important aspect in management of labour of such patients.

PIP: The feasibility of vaginal delivery after a previous lower-segment cesarean section (LSCS) delivery was investigated in a prospective partographic study of 100 women with a LSCS history. Cervical dilatation, effacement, and fetal head descent were evaluated every 2-4 hours by vaginal examination and the results were recorded on the labor partogram. 84 of these women were able to deliver vaginally; the remaining 16 required repeat LSCS. The main indications for repeat LSCS were fetal distress (6 cases) and right occipitoposterior presentation (4 cases). The mean duration of the first stage of labor was significantly prolonged in women with one previous LSCS only compared with those with intercurrent vaginal deliveries. The mean initial and average dilatation rates were 0.96 and 1.41 cm/hour, respectively, among women who delivered vaginally and 0.44 and 0.42 cm/hour, respectively, in those who had a repeat LSCS. All women with an initial dilatation rate of 1 cm or more per hour and 96% of those with an average dilatation rate of 0.5 cm or more per hour delivered vaginally. 87.5% of women who required LSCS crossed the partogram's alert line compared with 34.5% of those who delivered vaginally. These findings confirm that vaginal delivery after cesarean section is both safe and successful in properly selected women. Partographic evaluation is an important tool in the management of the labor and delivery of previous LSCS patients.

Purification and characterization of a low molecular weight zinc binding protein from human placenta.

A low molecular weight, native zinc binding, cytosolic protein (LMZP) has been isolated, purified and characterized from human normal term placenta. Gel filtration of heat treated placental cytosol after sequential acetone precipitation (80% ppt) revealed a major zinc binding protein in the range of low molecular weight. This partially purified zinc binding fraction was further fractionated on DEAE-Sephadex A-25. The zinc was eluted in one of the three peak fractions. Further, the purity of zinc binding protein was confirmed on fast protein liquid chromatography (FPLC). The purified placental LMZP was homogenous on SDS-polyacrylamide gel electrophoresis with a single band. Ultraviolet (UV) spectrum of LMZP showed an absorption maximum at 257 nm which disappeared at pH 2. Molecular weight of LMZP as determined by gel chromatography, SDS-polyacrylamide gel electrophoresis and amino acid analysis was 6 kDa. It was calculated that 1 g atom of zinc was bound to 1 mole of the LMZP. Unlike in classical metallothionein, the amino acid composition of placental LMZP revealed the presence of aromatic amino acids, lower content of cysteine and higher content of histidine, glutamic acid and aspartic acid (10, 9 and 5 residues/mole, respectively).

Significance of serum iron levels as a biochemical marker in pregnancy-induced hypertension.

OBJECTIVE: To determine the changes in serum iron levels, if any, as a biochemical marker of pregnancy-induced hypertension (PIH). METHOD: Fifty-four primigravidas with PIH formed the study group and 20 normotensive primigravidas comprised the control group in a prospective study. Serum iron levels were estimated at diagnosis of PIH, at termination of pregnancy and in the postpartum period. Data was analyzed using Student's t-test, the chi 2-test and regression analysis. RESULTS: Subjects with PIH were found to have higher serum iron levels at diagnosis of PIH (recruitment value) and at termination of pregnancy than the controls (P < 0.001). Serum iron levels in the PIH subjects decreased markedly in the postpartum period simultaneously with the clinical recovery from PIH. Serum iron values of > or = 110 micrograms/dl was found to differentiate PIH from normotensive pregnancies with a sensitivity and specificity of 89% and 90%, respectively. CONCLUSIONS: Changes in serum iron levels correlated with the clinical course of PIH and appeared to be a uniform and specific biochemical marker of PIH although its correlation with the severity of PIH was found to be poor.

Tinidazole prophylaxis in elective abdominal hysterectomy.

OBJECTIVE: To determine whether a single dose (2 g) of tinidazole before abdominal hysterectomy could reduce the incidence of postoperative infection. METHOD: A randomized double-blind placebo-controlled study was undertaken with a single oral dose (2 g) of tinidazole, 12 h before surgery, in 100 patients undergoing abdominal hysterectomy for various benign diseases. Other antibiotic use was withheld until there was no postoperative infection. RESULT: A significant reduction (P < 0.05) of infectious morbidity (28% vs. 8%) as well as a decrease in additional antibiotic use (P < 0.01) and duration of hospital stay (P < 0.001) was observed. Febrile morbidity was also reduced from 36% to 14% (P < 0.05). Tinidazole was tolerated well by all the patients. CONCLUSION: Tinidazole prophylaxis (2 g oral dose) is considered to be a simple, safe and effective way to reduce postoperative infection in abdominal hysterectomy.

Pregnancy in association with mitral valve prolapse.

Mitral valve prolapse (MVP) is considered to be the most common valvular heart lesion in adult females of reproductive age. Our report reviews the obstetrical performance and outcome of 34 pregnancies in 15 women with MVP. In 12 (80%) patients cardiac lesion was suspected due to enigmatic dyspnoea and palpitation during antenatal period. Four mothers required propranolol for cardiac arrhythmias. However, all of them tolerated pregnancy and labour well. Four pregnancies (11.8%) ended in spontaneous abortion and 1 mother had intrauterine fetal death due to severe pregnancy-induced hypertension. There were 25 (73.5%) term and 3 (8.8%) preterm neonates without congenital abnormality. One preterm neonate had tracheo-oesophageal fistula and died 6 hours after corrective surgery. The mean birth weight of 2.8 kg was appropriate for mean gestation of 38.5 weeks when compared to the Institute's reference neonatal weight curve. Infective endocarditis prophylaxis was recommended in cases having mitral regurgitation and complicated delivery. Awareness of this common cardiac lesion, thorough cardiovascular examination during pregnancy, early detection and treatment of cardiac arrhythmias if any, are the essential steps to prevent rare but dreaded maternal complications.

Childbirth following primary cesarean section--evaluation of a scoring system.

Of 1184 cases with previous cesarean section, 590 were selected for trial of vaginal delivery and 594 for repeat cesarean section. Of the former group, 76.6% had successful vaginal delivery. Incidence of uterine wound dehiscence and of perinatal mortality was highest in cases with primary classical cesarean section. Factors like indications for previous cesarean section, history of intercurrent vaginal delivery, weight of baby and period of gestation had positive correlation with delivery outcome.

Pathological changes in fallopian tubes following three different kinds of occlusive techniques in primates.

A comparative evaluation of three different techniques (Madlener's, Wood's and Filshie Clip Mark IV) for female sterilization was carried out in adult female rhesus monkeys with the aim of finding out the efficacy and the extent of tissue damage in the fallopian tube. The severity of pathological changes would indicate the chances of future successful reversal. The experiment was carried out in two phases. In Phase-I, no post-operative antibiotics were given whereas in Phase-II in addition to post-operative antibiotics, two sham-operated controls were also kept. This study revealed that the Filshie's clip is associated with significantly (p less than 0.01-0.001) greater tissue damage of the fallopian tubes with formation of dense adhesions as compared to the Madlener's or Wood's technique. Further, Filshie's clip had slipped off from 4 tubes out of 14 tubes where it was applied.

Effects of 17 beta-estradiol and progesterone on intestinal digestive and absorptive functions in ovariectomized rats.

The effects of low and high doses of 17 beta-estradiol and progesterone for 2 weeks on intestinal digestive and absorptive functions have been investigated in ovariectomized rats. The uptake of glucose was significantly enhanced following ovariectomy and administration of hormones restored the level of glucose uptake to that observed in sham-operated animals. Neither, the uptake of L-leucine nor calcium was affected after ovariectomy and treatment with the hormones. The activity of alkaline phosphatase (AP) of ileum was significantly elevated with the low and high doses of 17 beta-estradiol but in jejunum only at high doses. Progesterone alone did not alter AP activity but the combination of this hormone and 17 beta-estradiol significantly enhanced the jejunal and ileal AP activities. It seems that activity of AP is mainly under the control of 17 beta-estradiol. The activity of ileal disaccharidases and leucine aminopeptidase were enhanced at high doses of 17 beta-estradiol alone or in combination with progesterone whereas in the jejunum only AP activity was increased significantly. The present study indicates that 17 beta-estradiol plays an important role in regulating the activities of intestinal digestive enzymes and it is the ileal enzymes which are more prone to its action.

Conservative vs. surgical management of septic abortion with renal failure.

The role of surgery in the management of postabortum renal failure complicated with extensive uterine sepsis, perforation or peritonitis is controversial. This study compares the course and final outcome of 14 patients (66.6%) conservatively managed with appropriate antibiotics, fluid or blood replacement and dialysis, with seven patients (33.3%) for whom hysterectomy or laparotomy was undertaken in addition. Whereas all 14 patients treated conservatively died as the result of uncontrolled septicemia, three of the seven surgical patients recovered completely. Extensive necrosis with perforation of the uterine wall was confirmed either at laparotomy or at autopsy in all 21 women. To reduce mortality, the authors recommend early surgical intervention for patients suffering from postabortum renal failure complicated with uterine sepsis or perforation.