Biomedical subjects

J C Allen

Publications and source records attributed to J C Allen.

At least 91 records · Page 5Linked to original sources

PubMed1996

Contemporary chemotherapy issues for children with brainstem gliomas.

Radiotherapy has remained the mainstay of treatment for children with intrinsic, diffuse pontine tumors in spite of over 20 years of clinical trials attempting to validate the additional role of chemotherapy. Conventional phase II clinical trials conducted in patients with recurrent or progressive brainstem gliomas using single chemotherapy agents such as cyclophosphamide, carboplatin, cisplatin, etoposide and thiotepa or combinations of chemotherapy agents have produced low response rates in the range of 15-20%. Preradiotherapy chemotherapy phase II trials in newly diagnosed patients have yielded similar results with a therapeutic window as long as 4 months. Preliminary data from protocols employing high-dose chemotherapy with stem cell support have also met with disappointment. The one published phase III trial conducted by the Children's Cancer Study Group comparing radiotherapy with radiotherapy plus chemotherapy (CCNU, vincristine and prednisone) failed to establish a benefit to multimodality therapy. Current studies include the use of radiosensitizing chemotherapy (carboplatin, estramustine and cisplatin) in newly diagnosed patients and more intensive neoadjuvant chemotherapy trials. Major advances in our management await insights into molecular vulnerability of high-grade gliomas.

Antineoplastic Agents↗

PubMed1996

Results of a prospective randomized trial comparing standard dose neuraxis irradiation (3,600 cGy/20) with reduced neuraxis irradiation (2,340 cGy/13) in patients with low-stage medulloblastoma. A Combined Children's Cancer Group-Pediatric Oncology Group Study.

PURPOSE: To determine in a prospective randomized trial the effect on survival, progression-free survival, and patterns of relapse of a decrease in the neuraxis radiation dose from 3,600 cGy in 20 fractions to 2,340 cGy in 13 fractions in patients with newly diagnosed medulloblastoma between 3 and 21 years of age with low T stage (T1, T2 and T3A), minimal postoperative residual tumor, and no evidence of dissemination (M0). METHODS AND MATERIALS: Between June 1986 and November 1990, the Children's Cancer Group and the Pediatric Oncology Group randomized 126 patients in a two-arm study comparing the two different doses of neuraxis irradiation. In both arms, the posterior fossa received 5,400 cGy in 30 fractions. All patients were staged with myelography, postoperative lumbar cerebrospinal fluid cytology, and postoperative contrast-enhanced cranial computerized tomography to ensure no evidence of dissemination and no more than 1.5 cm3 residual tumor volume. Overall survival, progression-free survival, and patterns of recurrence were carefully monitored. Prospective endocrine and psychometric studies were performed to determine the benefit of decreasing the neuraxis radiation dose. RESULTS: Following an interim analysis at a median time on study of 16 months, the study was closed, since a statistically significant increase was observed in the number of all relapses as well as isolated neuraxis relapses in patients randomized to the lower dose of neuraxis radiation. CONCLUSIONS: In patients with newly diagnosed medulloblastoma considered to have a good prognosis on the basis of low T stage, minimal residual tumor after at least subtotal resection, and no evidence of dissemination after thorough evaluation, there is an increased risk of early relapse associated with lowering the dose of neuraxis radiation from 3,600 cGy in 20 fractions to 2,340 cGy in 13 fractions.

Adolescent↗

PubMed1996

Intramedullary spinal cord tumors in children under the age of 3 years.

Over a 13-year period extending from 1980 to 1993, 27 children less than 3 years of age underwent operation for removal of an intramedullary spinal cord tumor (IMSCT). The majority (18 of 27) of children had undergone surgery before being referred to New York University (NYU) Medical Center. The most common reasons for radiological investigation were pain (42%), motor regression (36%), gait abnormalities (27%), torticollis (27%), and progressive kyphoscoliosis (24%). Forty procedures were performed in 27 children. Nine children underwent two operations and two children underwent three procedures. A gross-total resection was achieved in 72% of the procedures. There was no surgical mortality. A comparison of the preoperative and 3-month postoperative functional grades for the first NYU procedure (NYU-1) yielded the following findings: 20 patients' conditions remained the same, five patients improved, and two patients deteriorated. The functional outcomes of a second operation (NYU-2) were similar. The majority of the children (24 of 27, 89%) had histologically determined low-grade lesions. There were 12 patients with low-grade astrocytomas (Grades I-III), eight with gangliogliomas, two with ganglioglioneurocytomas, one with a glioneurofibroma, and one child with a mixed astro/oligodendroglioma. Two children had anaplastic astrocytomas (Grades II-III) and one child had a glioblastoma multiforme. In a median follow-up review of 76 months, two patients died and two patients were lost to follow up. The 3- and 5-year progression-free survival (PFS) rates were 81.7% (standard error of the mean (SEM) 0.083) and 76.2% (SEM 0.094), respectively. Eight of 24 patients suffered a recurrence within a mean time of 45.4 +/- 28.9 months. All were treated with surgery (NYU-2). Lesions recurred in three of 12 children with low-grade astrocytomas, two of eight children with gangliogliomas, one child with an anaplastic astrocytoma, one child with a ganglioglioneurocytoma, and one child with a glioblastoma multiforme. At follow-up review, most of these children were doing well. Sixteen are in functional Grades I or II and 18 children attend a normal school system. The authors conclude that surgery for the removal of IMSCTs in children less than 3 years of age can be performed radically and safely. The postoperative functional performance is determined by the degree of the preoperative deficit. It is, therefore, of utmost importance to diagnose and treat these children as early as possible. Spinal cord tumors should be recognized as potentially excisable lesions on their initial presentation and when they recur. The optimum treatment for malignant lesions is still to be determined.

Child, Preschool↗

PubMed1995

Insulin-stimulated glucose transport inhibits Ca2+ influx and contraction in vascular smooth muscle.

BACKGROUND: Insulin attenuates serotonin-induced Ca2+ influx, the intracellular Ca2+ transient, and contraction of cultured vascular smooth muscle cells from dog femoral artery. These studies were designed to test whether insulin-induced glucose transport was an early event leading to the inhibitory effects of insulin on Ca2+ influx, intracellular Ca2+ concentration, and contraction in these cells. METHODS AND RESULTS: Insulin 1 nmol/L stimulated the 30-minute uptake of [3H]2-deoxyglucose in these cells via a phloridzin-inhibitable mechanism. Contraction of individual cells was measured by photomicroscopy, intracellular Ca2+ concentration was monitored by measuring fura 2 fluorescence by use of Ca(2+)-sensitive excitation wavelengths, and Ca2+ influx was estimated by the rate of Mn2+ quenching of intracellular fura 2 fluorescence when excited at a Ca(2+)-insensitive wave-length. In the presence of 5 mmol/L glucose, preincubation of cells for 30 minutes with 1 nmol/L insulin inhibited 10(-5) mol/L serotonin-induced contraction of individual cells by 62% (P < .01) and decreased the serotonin-stimulated component of Mn2+ influx by 78% (P < .05). Removing glucose from the preincubation medium or adding 1 mmol/L phloridzin completely eliminated these effects of insulin. Insulin lowered the serotonin-induced intracellular Ca2+ peak by 37% (P < .05), and phloridzin blocked this effect of insulin. When glucose uptake was increased to the insulin-stimulated level by preincubation of the cells for 30 minutes with 25 mmol/L glucose in the absence of insulin, serotonin failed to stimulate Mn2+ influx, the serotonin-induced Ca2+ peak was decreased by 46% (P < .05), serotonin-induced contraction was inhibited by 60% (P < .01), and addition of insulin did not further inhibit contraction. CONCLUSIONS: Since the effects of insulin on serotonin-stimulated Ca2+ transport, intracellular Ca2+ concentration, and contraction were dependent on glucose transport and were duplicated when glucose transport was stimulated by high extracellular glucose concentration rather than insulin per se, it is concluded that insulin-stimulated glucose transport is an early event that leads to decreased Ca2+ influx and contraction in vascular smooth muscle.

Animals↗

PubMed1995

Free zinc concentration in bovine milk measured by analytical affinity chromatography with immobilized metallothionein.

A new analytical affinity chromatography method was developed for measuring the free [Zn2+] concentration in bovine milk. The column was generated by immobilizing avidin and attaching biotinylated metallothionein (MT) on controlled-pore glass beads. Zinc bound to the MT column at physiological free [Zn2+] concentration and was dissociated again in an elution buffer of pH 2. The distributions of extrinsically added 65Zn and native zinc in different fractions of milk were virtually identical, validating the use of extrinsic labeling in studies of the free [Zn2+] concentration in milk. Extrinsically labeled whey fractions were mixed with standard solutions whose free [Zn2+] concentrations were calculated by computer model. 65Zn retained by the column provided an indication of free [Zn2+] concentration in the mixture, and by interpolation, in the original milk. The free [Zn2+] concentration measured by the affinity chromatography method in the milk of a group of six cows was 90.4 +/- 29.7 pM. This value is similar to estimates of free [Zn2+] concentrations in other biological fluids by entirely different methods. Measurement of free [Zn2+] may be helpful in understanding the physiology and biochemistry of zinc metabolism.

Animals↗

PubMed1995

A novel dialysis procedure measuring free Zn2+ in bovine milk and plasma.

A dialysis method was developed for measuring free Zn2+ concentration in plasma and milk for determination of the electrochemical gradient for Zn2+ across the mammary gland. This method used the zinc content of casein after dialysis as the metal ion indicator because zinc in the calcium phosphate-citrate complex inside casein micelles is dependent on the free Zn2+ concentration of an associated aqueous phase. Zinc, calcium and magnesium distribution in milk confirmed the high zinc binding by bovine casein. Zinc in the casein, dialyzed against standards or unknowns, was measured by atomic absorption spectrophotometry. Average free Zn2+ concentrations measured by the dialysis method in plasma and milk of five cows were 0.141 and 0.331 nmol/L, respectively. The equilibrium potential of Zn2+ ions across the mammary epithelium, calculated from free Zn2+ concentrations in blood and milk measured by the dialysis method, was -11.4 mV, consistent with the mammary electrical potentials noted in previous studies. Therefore, no electrochemical gradient for zinc between the two compartments was apparent, and it is not necessary to invoke an active transport mechanism in the mammary gland to explain the higher zinc concentration in milk than in plasma of most species.

Animals↗

PubMed1995

A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors.

PURPOSE: Cyclophosphamide is commonly used in the treatment of children with malignant brain tumors. The purpose of this study was to develop a multicycle, high-dose intensity cyclophosphamide regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) and to assess its activity against malignant glioma and primitive neuroectodermal tumor (PNET). METHODS: Twenty-three patients with brain tumors, including 15 with malignant glioma and six with PNET, were enrolled. Cyclophosphamide (1.8-2.25 g/m2/day for 2 days i.v.; total dose 3.6-4.5 g/m2) was administered and was followed by recombinant human GM-CSF (5 micrograms/kg/day s.c.) on days 3-11 or until the absolute granulocyte count reached 1.5 x 10(9)/L. RESULTS: With a total of 83 cycles administered, the mean dose intensity of cyclophosphamide ranged from 1.5 g/m2/week through cycle 2 (22 patients) to 0.8 g/m2/week through cycle 8 (two patients). No activity was seen against malignant glioma, and five of six patients with PNET had partial responses. The mean duration of a neutrophil count of < 0.5 x 10(9)/L was only 8 days; the platelet recovery was substantially longer. Fever during neutropenia occurred in 54 of 83 cycles. One patient died from transfusion-related graft-versus-host disease. CONCLUSIONS: A cyclophosphamide regimen equal to twice the dose intensity of that used in conventional therapy was administered. The regimen was active against PNET but inactive against malignant glioma.

Adolescent↗

PubMed1995

Survival and prognostic factors following radiation and/or chemotherapy for primitive neuroectodermal tumors of the pineal region in infants and children: a report of the Childrens Cancer Group.

PURPOSE: To describe the biologic and clinical features of children with primitive neuroectodermal tumors (PNETs) arising in the pineal region (pineoblastomas) and evaluate prospectively the efficacy of radiation therapy (RT) and/or chemotherapy. PATIENTS AND METHODS: Between 1986 and 1992, 25 children with PNETs of the pineal region were treated as part of a Childrens Cancer Group study. Eight infants less than 18 months of age were nonrandomly treated with eight-drugs-in-1-day chemotherapy without RT. The remaining 17 patients were treated with craniospinal RT and randomized to receive either vincristine, lomustine (CCNU), and prednisone or the eight-drugs-in-1-day regimen. RESULTS: Of 24 completely staged patients, 20 (83%) had localized disease at diagnosis. All infants developed progressive disease a median of 4 months from the start of treatment. Of the 17 older patients treated with RT and chemotherapy, the Kaplan-Meier estimate of progression-free survival (PFS) at 3 years is 61% +/- 13%. This is superior to the PFS of children with other supratentorial PNETs (P = .026). Following RT, 12 of 17 patients (70.6%) had a residual pineal region mass, which persisted for as long as 5 years before resolving; only four subsequently developed progressive disease. CONCLUSION: (1) Eight-in-1 chemotherapy without RT appears to be ineffective therapy for young children with PNETs of the pineal region. (2) For children more than 18 months of age at diagnosis treated with craniospinal RT and chemotherapy, the PFS is superior to that of children with other supratentorial PNETs. (3) A residual enhancing mass following RT is not predictive of treatment failure.

Adolescent↗

PubMed1995

Restrictive lung disease following treatment for malignant brain tumors: a potential late effect of craniospinal irradiation.

PURPOSE: To examine the effects of lomustine (CCNU), a commonly used nitrosourea, and craniospinal radiation therapy on the subsequent development of restrictive lung disease (RLD) following treatment for malignant brain tumors. PATIENTS AND METHODS: Pulmonary function testing with measurement of lung volume, spirometry, and diffusion capacity was performed in 28 patients who had received CCNU and/or radiation therapy as treatment for a malignant brain tumor. The median age at the time of treatment was 11.4 years (range, 3.9 to 36.7) and radiation therapy was completed 6 months to 11.6 years (median, 2.6 years) before testing. Patients were divided into four groups based on prior therapy. Group 1 received involved-field irradiation and a CCNU-containing chemotherapy regimen (n = 7); group 2, craniospinal irradiation with a boost to the primary tumor site and a CCNU-containing chemotherapy regimen (n = 6); group 3, craniospinal irradiation with a boost to the primary tumor site and a non-CCNU-containing chemotherapy regimen (n = 7); and group 4, craniospinal irradiation with a boost to the primary tumor site without chemotherapy (n = 8). RESULTS: Fourteen patients (50%) had findings consistent with RLD. One of seven patients (14.3%) who received CCNU without spinal irradiation had RLD, whereas 13 of 21 (61.9%) who received spinal irradiation with or without CCNU had RLD (P = .038), including four of eight patients treated with craniospinal irradiation alone. Logistic regression analysis showed that only spinal irradiation was a significant predictor for RLD. Patients who received spinal irradiation were 4.3 times more likely to have RLD than those who did not receive spinal irradiation. CONCLUSION: Spinal irradiation may be a risk factor for the development of RLD.

Adolescent↗

PubMed1995

Prognostic factors and treatment results for supratentorial primitive neuroectodermal tumors in children using radiation and chemotherapy: a Childrens Cancer Group randomized trial.

PURPOSE: To determine clinical characteristics and response to treatment for children with supratentorial primitive neuroectodermal tumors (S-PNETs). PATIENTS AND METHODS: After surgery and staging, 55 patients aged 1.5 to 19.3 years with S-PNETs were randomized to receive craniospinal radiotherapy (RT) followed by eight cycles of 1-(2-chloro-ethyl)-3-cyclohexylnitrosourea (CCNU), vincristine (VCR), and prednisone (standard treatment) or two cycles of 8-in-1 chemotherapy followed by RT and then eight additional cycles of 8-in-1. RESULTS: Three-year Kaplan-Meier estimates (estimate +/- SE) of survival and progression-free survival (PFS) rates for patients with confirmed diagnoses of S-PNET were 57% +/- 8% and 45% +/- 8%, respectively; survival and PFS rates for children with PNETs located in the pineal region were 73% +/- 12% and 61% +/- 13%, respectively, and were significantly different from the other S-PNETs (P < .03). The 8-in-1 arm had greater toxicity than the standard-treatment arm. Distributions of PFS between the two treatment groups were not significantly different (P > .5). Other univariate prognostic factors that influenced PFS included metastasis (M) stage (P < .03: M0 50% +/- 9% v M1-4 0%) and age (P < .02: 1.5 to 2 years 25% +/- 13% v > or = 3 years 53% +/- 9%). CONCLUSION: In this first randomized treatment trial for S-PNETs in children, no significant differences were detected between the two treatment groups. M0 and pineal site of involvement were independent predictors of a better outcome. However, survival was better than previously reported.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

A phase II trial of preirradiation carboplatin in newly diagnosed germinoma of the central nervous system.

BACKGROUND: Central nervous system (CNS) germinomas respond readily to both radiotherapy and chemotherapy. This study was designed to selectively reduce the dose of radiotherapy in those patients expressing a complete response (CR) to neoadjuvant carboplatin. METHODS: A Phase II trial with carboplatin was conducted in 11 newly diagnosed patients with histologically confirmed, radiologically evaluable CNS germinomas before they received radiotherapy. All patients had normal cerebrospinal fluid and serum tumor markers (i.e., human chorionic gonadotropin [HCG] and alpha fetoprotein [AFP]). Seven patients had localized tumors (three pineal, three suprasellar, and one thalamus), and four had multifocal disease. Their median age at diagnosis was 13 years (range, 7-31). One course of carboplatin consisted of 150 mg/m2 weekly for 4 consecutive weeks followed by a 2-week break. Response was evaluated after two courses. If a patient had a CR to chemotherapy, the radiotherapy doses to the involved field and the craniospinal axis were lowered from 50 Gy to 30 Gy and from 36 Gy to 21 Gy, respectively. If less than a CR was observed, two additional courses of chemotherapy were administered, after which the patient's response was reevaluated. Less than a CR required full radiotherapy doses. The radiotherapy volume was determined by the extent of disease at diagnosis (i.e., localized disease was treated with an involved field and craniospinal therapy was used for disseminated disease). RESULTS: Seven patients had a CR to carboplatin (five patients after two courses and two patients after four courses). Three patients had a partial response (one after four courses and two after two courses). The investigators of the latter two patients chose not to give additional chemotherapy. Another patient opted for radiotherapy after receiving only one course of chemotherapy and was not evaluable for response. Ten of 11 patients remain in continuous remission for a median of 25 months. One patient had a recurrence. He presented with a localized pineal germinoma and had a CR after two courses of carboplatin. He received 30 Gy of involved field radiotherapy and suffered a relapse 5 months later in multiple CNS sites. He died 23 months after diagnosis with diffuse CNS and peritoneal metastases. His serum AFP and HCG levels were elevated, consistent with a nongerminoma germ cell tumor. CONCLUSIONS: Carboplatin was highly active in treating newly diagnosed CNS germinomas. Further chemotherapy studies eventually may permit additional dose reductions and/or elimination of radiotherapy for patients with CNS germinomas.

Adolescent↗

PubMed1994

Tissue specific membrane association of alpha 1T, a truncated form of the alpha 1 subunit of the Na pump.

We have assessed the Na pump alpha-subunit isoform content utilizing site directed antibodies in two vascular smooth muscle (VSM) preparations known to contain functional Na pump sites, VSM microsomal fractions (Na+, K(+)-ATPase) and intact primary confluent cells (ouabain inhibited 86Rb uptake). A comparison of isoform content was made with kidney microsomes. Both VSM and kidney microsomes contained a full length alpha 1 subunit (approximately 100 kDa) as well as a truncated subunit, alpha 1T (approximately 66 kDa). SDS treatment of VSM microsomes effected an increase in Na+, K(+)-ATPase and a retention of alpha 1T. SDS treated kidney microsomes retained the alpha 1 isoform and Na+, K(+)-ATPase. Confluent VSM cells showed no detectable alpha 1, only alpha 1T. In the absence of detectable full length alpha 1, the alpha 1T protein may represent a functional Na pump component in canine VSM.

Animals↗

PubMed1994

Pre-irradiation chemotherapy in children with high-grade astrocytoma: tumor response to two cycles of the '8-drugs-in-1-day' regimen. A Childrens Cancer Group study, CCG-945.

PURPOSE: This study was undertaken to evaluate the radiographic response to two cycles of chemotherapy prior to irradiation in newly diagnosed children with high-grade astrocytomas. PATIENTS AND METHODS: One hundred and thirty children less than 21 years of age with newly-diagnosed high-grade astrocytoma were treated with the 'eight-drugs-in-one-day' chemotherapy regimen as part of a phase III multi-institutional Childrens Cancer Group (CCG) trial. Computerized Tomographic (CT) or Magnetic Resonance Image (MRI) scans, obtained after two cycles of chemotherapy had been administered, were compared with post-operative scans to determine treatment response. Scans were evaluated by institutional radiologists, and were reviewed centrally by a single neuroradiologist. RESULTS: Of 79 patients with evaluable post-operative residual tumor on CT or MRI scans, 26 (33%) were determined on institutional evaluation to have had an objective response. However, central review of scans documented responses on only 14/79 (18%). A significantly higher response rate on central review was observed for those children 36 months of age or less at study entry than for older children (33% v 11%; p < 0.001). However, a higher disease progression rate was also observed for those children 36 months of age or less than for older children (21% v 2.6%; p < 0.001). CONCLUSION: In this study, the largest yet reported in newly-diagnosed children with high-grade astrocytomas, the chemotherapy regimen has activity in younger children. The differences in response rates reported by institutional and central review highlight the difficulties inherent in assessing response to brain tumor therapy. However, the study does demonstrate the consistent ability of radiologists to identify disease progression within the institutional and central reviews.

Adolescent↗

PubMed1994

Post-traumatic small bowel obstruction.

Small bowel stenosis due to blunt abdominal trauma is rare. This paper reports a Gurkha soldier who sustained apparently minor trauma in a flying accident and presented 11 weeks later with abdominal pain. After extensive investigations, a post-traumatic small bowel stricture was identified and excised.

Abdominal Injuries↗

PubMed1994

Insulin inhibits serotonin-induced Ca2+ influx in vascular smooth muscle.

BACKGROUND: Insulin in physiological concentrations attenuates the agonist-induced intracellular Ca2+ ([Ca2+]i) transient and inhibits contraction in individual nonproliferated cultured canine femoral artery vascular smooth muscle cells (VSMCs). In the present study, we wished to define the effects of insulin on individual components of Ca2+ transport in vascular smooth muscle. METHODS AND RESULTS: Insulin (40 microU/mL) attenuated the 5-hydroxytryptamine (5-HT, serotonin; 10(-5) mol/L)-induced [Ca2+]i transient (measured by fura 2 fluorescence) in primary confluent canine femoral artery VSMCs in the presence of extracellular Ca2+. In Ca(2+)-free media, the 5-HT-induced [Ca2+]i transient was reduced by 42% and was not affected by insulin. This finding suggested that insulin inhibits 5-HT-induced Ca2+ influx but does not affect sarcolemmal Ca2+ efflux or Ca2+ release from intracellular stores. In support of those conclusions, we found that insulin inhibited the 5-HT-induced component of Mn2+ (a Ca2+ surrogate) influx (measured by fura 2 fluorescence quenching at the Ca2+ isosbestic excitation wavelength). In addition, 5-HT stimulated the rates of 45Ca2+ efflux from intact cells (a measure of sarcolemmal Ca2+ efflux) and from saponin-permeabilized cells (a measure of Ca2+ release from intracellular stores), but insulin did not affect these rates of 45Ca2+ efflux. CONCLUSIONS: We conclude that a physiological insulin concentration attenuates the 5-HT-induced [Ca2+]i transient in confluent primary cultured canine femoral artery VSMCs by inhibiting the 5-HT-induced component of Ca2+ influx but not by affecting sarcolemmal Ca2+ efflux or Ca2+ release from intracellular stores.

Animals↗

PubMed1994

Quality assessment of urinary organic acid analysis.

The number of known inherited metabolic disorders resulting in an organic aciduria has increased steadily over the past two decades. Prompt and reliable detection is both clinically and technically demanding but is essential if appropriate treatment is to be undertaken. This is the first study of laboratory performance in the detection of these disorders to be undertaken in the UK. Some conditions were accurately identified by most laboratories: for example for maple syrup urine disease, 12 of 14 laboratories provided an appropriate response and medium chain acyl-CoA dehydrogenase deficiency was correctly identified by 15 of 17 laboratories. However, accuracy of detection was poorer for other conditions: for example, only eight of 17 laboratories detected tyrosinaemia type 1 and nine of 18 laboratories detected 4-hydroxybutyric aciduria. The strongest correlation with good performance was obtained by comparison with the extent of peak identification: r = 0.62, P = 0.002. The need for regular attendance at scientific symposia was also supported by a weaker positive correlation with the average score achieved, P = 0.08. Evidence also suggested that some of the laboratories with a low workload performed less well. No significant difference in performance could be demonstrated between the 17 laboratories who used gas chromatography-mass spectrometry and the six participants who used gas chromatography alone.

Acyl-CoA Dehydrogenase↗

PubMed1994

Survival of infants with primitive neuroectodermal tumors or malignant ependymomas of the CNS treated with eight drugs in 1 day: a report from the Childrens Cancer Group.

PURPOSE: Very young children with CNS primitive neuroectodermal tumors (PNETs) and ependymomas have a poor prognosis and commonly have impairment of growth and cognitive abilities, in part resulting from radiotherapy. Thus, an intensive chemotherapeutic regimen was used to treat children less than 18 months of age at diagnosis. PATIENTS AND METHODS: Children were treated on a Childrens Cancer Group (CCG) protocol with an eight-drug chemotherapeutic regimen (vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytarabine, prednisone, and cyclophosphamide) following surgery and postoperative staging. Delayed or reduced-volume radiotherapy was to be administered to all patients, but, in fact, was omitted in most cases. RESULTS: On central review of pathology, 82 children had diagnosis concordant with study entry criteria. Of these, 46 (56%) had posterior fossa (PF) PNET, eight (10%) had pineal PNET, 11 (12%) had nonpineal supratentorial PNET, 15 (18%) had ependymoma, and two had rhabdoid tumors. Fifty percent of tumor resections were complete, as verified by postoperative computed tomographic (CT) scan, and 23% of patients had metastatic disease at the time of diagnosis. Objective tumor response was documented following two cycles of chemotherapy in 28% of assessable patients. Toxicity of chemotherapy was primarily hematopoietic. Five children died of chemotherapy-related complications. Radiotherapy was administered to only nine patients before tumor progression. The 3-year progression-free survival (PFS) rates for PF PNET, pineal PNET, supratentorial nonpineal PNET, and ependymoma are 22% (SE = 6%), 0%, 55% (16%), and 26% (11%), respectively. The 3-year PFS rate for those children without metastatic disease was 29% (6%), as compared with 11% (6%) for those with metastatic disease. The only independent predictors of PFS were metastasis stage and location of the tumor within the pineal region. The median time to progression was 6 months. Twenty-four children completed the chemotherapeutic regimen without tumor progression; 19 are event-free survivors more than 2 years from diagnosis, only three of whom received radiation therapy. CONCLUSION: While overall survival in this group of very young patients is poor, a subset of children who have received only chemotherapy as adjuvant treatment remain free from tumor recurrence.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Cervicomedullary tumors in children: a distinct subset of brainstem gliomas.

We reviewed the clinical course of 17 children who underwent surgical resection of an intra-axial cervicomedullary tumor between 1980 and 1992. The clinical symptoms, which reflected medullary dysfunction in nine children and cervical cord deficits in eight, were present for a mean of 2.1 years before diagnosis (range, 2 months to 7.5 years), and for at least 1 year in 80% of the patients. Neurodiagnostic imaging (MRI in 14, CT in 3) showed the tumor epicenter in the medulla in 11 and in the upper cervical cord in six. Surgery was performed for newly diagnosed tumor in 11 children, and for progressive disease in six who had received prior radiotherapy. The surgical resection was gross total in two and partial (60 to 95%) in fifteen. Fifteen patients had low-grade glial tumors (10 astrocytomas, four gangliogliomas, and one mixed glioma), and two had anaplastic gangliogliomas. Four-year progression-free and total survival rates after surgery for patients who had surgery as initial therapy were 70 and 100%; for those who had surgery at the time of progression, these were 41 and 62%. Postsurgical neurologic complications occurred in five children. Four of these children had received prior radiotherapy. Two of them already had severe preoperative deficits and three had moderate deficits that worsened after surgery. Twelve patients with mild deficits were unchanged or improved postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗