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Biomedical subjects

J Krischer

Publications and source records attributed to J Krischer.

At least 73 records · Page 4Linked to original sources
PubMed1988

Clinical trial of etoposide (VP-16) in children with recurrent malignant solid tumors. A phase II study from the Pediatric Oncology Group.

Etoposide (VP-16), 150 mg/M2, given intravenously daily for 3 days every 3 weeks resulted in 3 complete responses and 6 partial responses in 154 patients with a spectrum of recurrent malignant solid tumors. There was evidence of disease control in an additional 37 patients (27 mixed responses and 10 stable disease). These responses occurred primarily in patients with Ewing's sarcoma, Hodgkin's disease, neuroblastoma and rhabdomyosarcoma. Most of the patients had every extensive prior therapy; however prior therapy with teniposide (VM-26), the congener of VP-16, did not seem to preclude responses to the latter drug. Myelosuppression was the principal form of toxicity. Neutropenia characterized by absolute neutrophil counts of 0.5 to 0.9 x 10(9)/L occurred in one-half of the patients, and thrombopenia with platelet counts of less than 25 to 49 x 10(9)/L in one-fourth. These results demonstrate a favorable therapeutic index for VP-16 in several recurrent childhood solid tumors, supporting its use as a component of primary therapy for these diseases.

Adolescent↗
PubMed1988

Hyperfractionated radiotherapy in brain stem tumors: results of a Pediatric Oncology Group study.

Between September 1984 and January 1986, 38 patients were entered onto the first phase of a Pediatric Oncology Group study designed to test the feasibility of treating children with brain stem tumors with hyperfractioned (twice daily) radiotherapy, to assess the early and late morbidity and efficacy of such treatment, and to test the feasibility of dose escalation in this group of patients. Of the 34 patients considered eligible after neuroradiology review, two did not complete planned radiotherapy because of progressive disease; both died of disease at 4 weeks and 9 months following initiation of treatment. The remainder were treated with 1.1 Gy twice daily, with an interval of 4 to 6 hours, to a total dose of 66 Gy in 60 fractions over 6 weeks. The majority of patients (24/34, 71%) improved clinically during the course of treatment; two remained stable, seven deteriorated, and for one the clinical response was unknown. By CT scan and/or MRI, no patient showed complete regression of disease; five showed a partial response to treatment, twenty fell into a stable disease category, eight patients developed progressive disease by the time of their first follow-up radiologic examination, and one patient was not evaluable for response, having been lost to follow-up immediately after completion of treatment. All five patients who achieved partial response and 17/20 patients in the stable, disease category subsequently progressed, after a median interval of 6.5 months. The median survival time was 11 months and survival at 1 year was 48% (SE 0.08). Morbidity of treatment consisted of an enhanced skin reaction in three patients, otitis media and/or externa in nine, and complications related to steroid intake in four, including diabetic ketoacidosis (two patients), Pneumocystis pneumonia (one patient), and disseminated varicella (one patient). Protracted use of steroids in 13 patients was associated in all instances with non responding or progressive disease. No patient developed signs or symptoms suggestive of CNS damage, and tissue obtained by biopsy at the time of progression in three patients and at autopsy in five failed to demonstrate any evidence of injury attributable to the radiotherapy. A dose escalation to 70.2 Gy in 60 fractions over 6 weeks was implemented as planned.

Adolescent↗
PubMed1987

Toxicity evaluation of dihydroxyanthracenedione (DHAD) in combination with cytosine arabinoside (Ara-C).

To determine optimal dosage, Dihydroxyanthracenedione (DHAD) was given once daily for 3 days at dosage levels of 6, 7, 8, and 10 mg/m2 in combination with a 7-day continuous infusion of cytosine arabinoside (Ara-C). Nineteen of 20 children with leukemia who received these agents developed fever requiring hospitalization. There were 4 deaths-2 due to proven infection. One patient developed nonfatal cardiotoxicity. No other significant toxicity was noted. Responses were seen in 7 of 20 patients. The recommended DHAD dosage was 8 mg/m2/day when given in combination with Ara-C.

Adolescent↗
PubMed1987

Combined etoposide and 5-azacitidine in children and adolescents with refractory or relapsed acute nonlymphocytic leukemia: a Pediatric Oncology Group Study.

An intensive regimen of combined etoposide (VP-16) and 5-azacitidine (5-Az) was used to treat 96 children and adolescents with refractory or relapsed acute nonlymphocytic leukemia (ANLL). Patients were given two sequential five-day courses of VP-16, 250 mg/m2 for three days, followed by 5-Az, 300 mg/m2 for two days. An additional five-day course was administered if marrow aplasia was not evident by day 13. A complete remission rate of 45% was achieved with a median of two courses of VP-16 and 5-Az. The outcome of induction therapy was not influenced by prior treatment, blast cell morphology, or disease status on study entry (refractory or relapsed). Twenty-seven patients have relapsed after remission periods of 35 to 920 days (median, 110 days); seven others are free of leukemia for up to 519 days. The effectiveness of VP-16/5-Az combination therapy in patients refractory to anthracyclines and cytarabine indicates a potential role for these compounds in first-line treatment of patients with ANLL.

Adolescent↗
PubMed1986

Hypothalamic-pituitary function of children with acute lymphocytic leukemia after three forms of central nervous system prophylaxis. A retrospective study.

The hypothalamic-pituitary function of 93 children, who had received central nervous system (CNS) prophylaxis as part of their therapy for acute lymphocytic leukemia (ALL), and who remained in continuous complete remission, was evaluated retrospectively. Treatment regimens included--Group I: 31 subjects, intrathecal methotrexate (IT MTX); Group II: 31 subjects, IT MTX plus 2400 rad cranial irradiation; and Group III: 31 subjects, IT MTX and intravenous intermediate-dose methotrexate. Serum thyroid-stimulating hormone (TSH) and T4 levels were normal. All participants had normal adrenocorticotropic hormone (ACTH) secretion as assessed by plasma cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) excretion of pubertal and postpubertal patients (N = 37) was appropriate, except for one subject from Group I who had an abnormally high output of gonadotropins, and one from Group II who had abnormally low levels. Growth hormone (GH) responses were subnormal after sequential arginine-insulin stimulation as follows--Group 1: 3 of 31 patients; Group II: 6 of 25 patients; and Group III: 2 of 29 patients. Nevertheless, all children had normal linear growth. It was concluded that the three forms of CNS prophylaxis evaluated had no long-term adverse effect on TSH and ACTH secretion. FSH-LH production appears to be normal, but final judgment must await follow-up studies because 60% of the patients were prepuberteral or still receiving chemotherapy. Eleven patients had subnormal GH responses after pharmacologic stimulation of the pituitary, but long-term linear growth was unaffected.

Adolescent↗
PubMed1986

Obstetric anesthesia: a national survey.

To assess obstetric anesthesia in the United States, and to determine why more anesthesia personnel are not involved in this subspecialty, a questionnaire was sent to the heads of obstetric and anesthesia services in 1,200 hospitals. Both obstetric and anesthesia respondents agreed on several characteristics of obstetric anesthesia that inhibit more participation by anesthesia personnel. Among others, they identified that: the unpredictability of labor and delivery makes scheduling difficult; obstetricians tend to dictate type and timing of anesthesia; the risk of malpractice claims is increased for obstetric anesthesia; and, finally, larger obstetric services would make it more practical to provide anesthesia services. Regarding availability of personnel and procedures, obstetric units with less than 500 deliveries per year were considerably more under-staffed than the larger units in most areas studied. When general anesthesia was used for cesarean section in these units, it was provided by, or given under the direction of, an anesthesiologist only 44% of the time, whereas in the hospitals with more than 1,500 deliveries per year, an anesthesiologist was present 86% of the time. Likewise, in the small units, personnel classified as "others" were responsible for newborn resuscitation in 24% and 43% of instances after cesarean section and vaginal delivery, respectively. In the hospitals with more than 1,500 deliveries, comparable figures were 4% and 2%, respectively.

Anesthesia, Epidural↗
PubMed1985

Computerized tomography scan findings in children with acute lymphocytic leukemia treated with three different methods of central nervous system prophylaxis.

Computerized tomography (CT) scans of the head were done on 93 children with acute lymphocytic leukemia in continuous complete remission who had been randomly assigned to three different methods. of central nervous system (CNS) prophylaxis. Twenty-nine children had received six doses of intrathecal methotrexate, 30 had received six doses of intrathecal methotrexate plus 2400 rad of cranial irradiation, and 34 had received six doses of intrathecal methotrexate plus three courses of intermediate-dose intravenous methotrexate. The overall incidence of abnormal scans was 35%, of which 91% were felt to represent minimal abnormalities. CT scan abnormalities were noted in 30% of the children receiving intrathecal methotrexate only, in 40% of those receiving intrathecal methotrexate plus cranial irradiation, and in 35% of those receiving intrathecal methotrexate plus intermediate dose methotrexate. These differences were not statistically significant. None of the three methods of CNS prophylaxis resulted in significant CT scan abnormalities. However, the few moderately or markedly abnormal scans evaluated were restricted to patients who received intrathecal methotrexate plus cranial irradiation. The clinical significance of CT scan abnormalities in leukemic children receiving these treatments remains unclear.

Brain Neoplasms↗
PubMed1984

Evaluation of AMSA in children with acute leukemia. A Pediatric Oncology Group study.

One hundred four children with advanced leukemia in relapse (74 with acute lymphocytic leukemia [ALL] and 30 with acute nonlymphocytic leukemia [ANLL]) received AMSA (4'-(9-Acridinylamino) methanesulfon -m-anisidide) at a dose of 120 mg/m2/day for 5 days (Regimen I) or 60 mg/m2/day for 10 days (Regimen II). Children with ALL were randomized between Regimens I and II (31 and 36 evaluable patients, respectively). All 29 evaluable patients with ANLL were treated on Regimen I. Eighty-eight percent of evaluable patients experienced severe or life-threatening toxicity, with no statistical differences between Regimens I and II. Bacterial or fungal infections (considered life-threatening or fatal) occurred in 17 children with ALL and in 7 with ANLL. Fatal cardiac toxicity occurred in one patient. Complete or partial response occurred in 25.0% (SE = 8.8%), 28.1% (SE = 8.0%), and 25.9% (SE = 8.4%) of evaluable patients on ALL Regimen I, ALL Regimen II, and ANLL, respectively. However, responses were of short duration (16-91 days). There was no significant difference in the duration of survival from treatment start for the two ALL regimens (P = 0.46). The median duration of survival for ANLL patients was significantly longer (P = 0.004) than that of ALL patients treated on Regimens I and II combined. Eighty-two percent of the complete or partial responses (18 of 22) occurred after the first course of AMSA. At the dose schedules investigated, and in a heavily pretreated patient population, AMSA had activity in childhood leukemia. However, the high incidence of severe, life-threatening, or fatal infections meant that the quality and quantity of responses and survival was not commensurate with the toxicity, and that it would be difficult to incorporate this drug into combination chemotherapy with other myelosuppressive agents.

Acute Disease↗
PubMed1984

The effect of advanced life support and sophisticated hospital systems on motor vehicle mortality.

A mileage population death index (MPDI) was devised to compare the death rate from motor vehicle trauma in Florida counties. The MPDI was defined as the average death rate per one hundred million miles driven divided by the population of the particular county X 10(5). The resultant MPDI was correlated with the presence in a county of basic life support only and advanced life support. In addition, counties with large metropolitan hospitals which might possibly classify as Level I institutions were compared with other counties. A low MPDI was found to be highly correlated with the presence of an ALS system (p = 0.001). Counties with hospitals which might qualify as Level I also had a significantly lower MPDI (p = 0.04). We conclude that the presence of advanced life support and a sophisticated hospital is correlated with a significantly lower motor vehicle mortality.

Accidents, Traffic↗