PubMed Health⌕ Search

Biomedical subjects

P A Koch

Publications and source records attributed to P A Koch.

At least 19 recordsLinked to original sources
PubMed2005

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts and treatment outcome in children with B-progenitor-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.

We reported that children with B-progenitor-cell acute lymphoblastic leukemia (BpALL) treated in the early 1980s whose lymphoblasts accumulated high levels of methotrexate (MTX) and of methotrexate polyglutamates (MTXPGs) in vitro had an improved 5-year event-free survival (EFS) (65% (standard error (s.e.) 12%) vs 22% (s.e. 9%)). We repeated this study in children with BpALL treated in the early 1990s. The major change in treatment was the addition of 12 24-h infusions of 1 g/M2 MTX with leucovorin rescue (IDMTX). In 87 children treated on Pediatric Oncology Group (POG) study 9005 and POG 9006, the 5-year EFS for those whose lymphoblasts accumulated high levels of MTX and MTXPGs (79.2%, s.e. 8.3%) was not significantly different from that of patients with lesser accumulation of MTX and MTXPGs (77.7%, s.e. 5.4%). These findings support the notion that higher dose MTX therapy has contributed to increased cure, particularly for patients whose lymphoblasts accumulate the drug less well.

Antimetabolites, Antineoplastic↗
PubMed1998

Accumulation of methotrexate polyglutamates, ploidy and trisomies of both chromosomes 4 and 10 in lymphoblasts from children with B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group Study.

Levels of accumulation of methotrexate polyglutamates were measured in vitro in lymphoblasts obtained at diagnosis from children with B-progenitor cell acute lymphoblastic leukemia (pro-B ALL). They were compared to numerical and structural chromosomal abnormalities present in these leukemic cells. In a series of 95 patients, the percent with high lymphoblast methotrexate polyglutamate levels increased with the increase in modal number of total chromosomes (p<0.001). Thus, lymphoblast methotrexate polyglutamate accumulation appeared to be closely linked to the extent of hyperdiploidy in childhood pro-B ALL. Lymphoblasts from 35 (88%) of the 40 children with hyperdiploid (>50 chromosomes) and 23 (88%) of 26 with hyperdiploid (DNA Index >1.16) pro-B ALL accumulated high levels of methotrexate polyglutamate, suggesting that they were more sensitive to methotrexate cytotoxicity. While children with hyperdiploid (DNA Index >1.16) pro-B ALL have a good prognosis, those with trisomies of both chromosomes 4 and 10, almost all of whom are hyperdiploid, have an even better outcome. There was no significant difference in methotrexate polyglutamate levels in lymphoblasts from 19 children with and 21 without trisomies of both chromosomes 4 and 10 (p = 0.25). The improved response to multi-agent chemotherapy conferred by the presence of trisomies of both chromosomes 4 and 10 in such patients may be due to increased sensitivity of their lymphoblasts to one or more anti-leukemic agents in addition to methotrexate.

Adolescent↗
PubMed1994

Is the social acceptability of psychiatric patients decreased by orofacial dyskinesia?

A group of psychiatric patients with and without orofacial dyskinesia (OFD) were filmed in pairs on videotape and a group of first-year social studies students were asked to select one candidate from each pair to fill a (simulated) job opening. A stationary picture (photograph) in which OFD was not visible and moving images (a video film) in which dyskinesia was visible were shown of each patient. The video effect, which was an indicator of the increase in popularity of a patient on the video film compared with the photograph, differed significantly between the OFD and control patients. Making the movement disability visible caused a relative decrease in the popularity of the OFD patients as opposed to an increase in the popularity of the control patients.

Adult↗
PubMed1993

Myoblast transfer in Duchenne muscular dystrophy.

One biceps muscle of 8 patients with Duchenne muscular dystrophy was injected at 55 sites with a total of 55 million viable, purified, and contamination-free normal myoblasts (myoblast transfer). The other biceps of each patient was injected with a placebo to serve as a control. The procedure was blinded to the patients, parents, and investigators. Myoblasts derived from a biopsy specimen of the fathers were cultured and purified under strict conditions and carefully screened for microbial contamination. All patients received cyclophosphamide for immunosuppression for 6 or 12 months. No serious complications were observed after myoblast transfer, indicating that the procedure is safe. The overall therapeutic efficiency of myoblast transfer was poor as judged by the results in maximal voluntary force generation, dystrophin content of the muscle, magnetic resonance imaging of the muscle, and the lack of donor-derived DNA and dystrophin messenger RNA in the injected muscle. An improved efficiency of the take of myoblasts might be achieved by using younger cells and injecting the myoblasts with a myonecrotic agent (to increase the prevalence of regeneration) and a basal laminal fenestrating agent.

Analysis of Variance↗
PubMed1990

Recombinant GM-CSF in patients with poor graft function after bone marrow transplantation.

Poor graft function after bone marrow transplantation is an infrequent complication that is fatal for most patients secondary to severe infections or to bleeding. Even a second marrow infusion is usually not successful in restoring hematopoiesis. We treated nine patients with recombinant Escherichia coli derived human granulocyte-macrophage colony-stimulating factor (GM-CSF) for delayed engraftment or graft failure after autologous (n = 6) or allogeneic (n = 3) bone marrow transplantation (BMT). Six patients were given a dose of 10 micrograms/kg/d over 30 min; three patients received lower doses of 3-5 micrograms/kg/d. Seven patients lived longer than 3 days after commencing GM-CSF and could be evaluated for their response. Six of them had a marked rise in neutrophil counts; there was no effect on platelet and reticulocyte counts. Two patients died within the first 3 days after starting GM-CSF, although both seemed to have some response to GM-CSF (increasing blood neutrophils in one, and increasing macrophages in the bone marrow on autopsy in the other). Side effects most likely attributable to GM-CSF administration were mild and included diarrhea and abdominal pain, low grade fever and mild rash. Severity of graft-vs-host disease (GVHD) was not enhanced in the recipients of allogeneic marrow. We conclude that recombinant GM-CSF can be safely given to patients with poor graft function after marrow transplantation. In some patients, this may lead to a subsequently sustained neutrophil recovery.

Adolescent↗
PubMed1986

Bone marrow transplantation in lymphomatoid granulomatosis. Report of a case.

Lymphomatoid granulomatosis is an unusual disorder histologically characterized by an angiocentric, angiodestructive mixed cellular infiltrate. The most frequent clinical manifestations are seen in the lungs, the skin, and the central nervous system. Progression to lymphoma may occur, particularly in patients who are anergic. The authors report the case of a boy who had had a splenectomy at 2 years of age for presumed Evan's syndrome, and two episodes of pneumococcal meningitis at 5 and 10 years of age. At 14 years, he had severe respiratory compromise, and a lung biopsy specimen showed lymphomatoid granulomatosis. The liver and bone marrow also were affected. Improvement occurred with multiagent chemotherapy, but he had multiple relapses. A bone marrow transplant was performed using a human leukocyte antigen (HLA) identical mixed lymphocyte culture (MLC) nonreactive brother as the donor. He remains in remission more than 3 years post-transplant. In addition, his abnormal immune function has improved.

Adult↗
PubMed1986

Bone marrow transplantation for children with acute leukemia and Down syndrome.

Four children with acute leukemia and Down syndrome received high-dose cyclophosphamide therapy and total body irradiation in preparation for bone marrow transplantation. Skin and mucous membrane toxicity was pronounced. Furthermore, three children died during the immediate posttransplantation period of infectious and hemorrhagic pulmonary complications. One patient had hematologic recovery and is surviving disease-free 1 year following transplantation. These preliminary observations are in agreement with previous data suggesting that children with Down syndrome are at higher risk for toxicity, pneumonitis, and, possibly, death following administration of intensive therapy for leukemia in comparison with children without Down syndrome. Improvements in the management of these children in the future will depend upon a better understanding of the biologic and pathophysiologic aspects of Down syndrome and additional clinical experience.

Adolescent↗
PubMed1984

Absorption of oral aminoglycosides following bone marrow transplantation.

Four patients with severe gastrointestinal reactions receiving oral "nonabsorbable" antibiotics for gut sterilization following bone marrow transplantation absorbed clinically significant amounts of aminoglycoside (gentamicin and/or tobramycin). Serum concentrations of 2.2, 2.6, 5.8, and 12.0 micrograms/ml were measured. Two of these patients had acute graft versus host reactions and two had severe mucositis following cytoreduction with intensive chemotherapy and irradiation. Nephrotoxicity occurred in the latter patients. One patient was studied in detail. Her hospital course and investigative results are presented. Four additional patients with mild gastrointestinal reactions following cytoreduction did not absorb gentamicin when their toxicity was maximal. Serum aminoglycoside determinations are necessary in patients receiving oral aminoglycosides for gut sterilization following bone marrow transplantation if moderate to severe gastrointestinal reactions occur.

Adolescent↗
PubMed1984

Pulmonary function in patients undergoing bone marrow transplantation.

Pulmonary function was studied prospectively in 25 children with leukemia and aplastic anemia undergoing bone marrow transplantation (BMT). Whereas 11 patients have died, only one did so primarily due to interstitial pneumonia. Fourteen patients (56%) survived a median of at least 36 months. Seventeen patients received pulmonary function tests (PFTs). Four patients transplanted for leukemia in relapse following preparation with a very intensive regimen (cyclophosphamide, 200 mg/kg, total body irradiation, 1,000 rad, BCNU, cytosine arabinoside) developed restrictive lung changes. Patients undergoing BMT for aplastic anemia and leukemia in remission prepared with more commonly used and less intensive regimens maintained normal pulmonary function. As new regimens are devised, PFTs should be utilized to characterize the pulmonary toxicity of these regimens as well.

Adolescent↗
PubMed1984

Treatment of advanced neuroblastoma with supralethal chemotherapy, radiation, and allogeneic or autologous marrow reconstitution.

Ten children with recurrent metastatic (stage IV) neuroblastoma received local radiation therapy, supralethal chemotherapy, and total-body irradiation. Rescue with infusions of either allogeneic (four patients) or autologous (six patients) bone marrow followed. The drugs given to the first two patients were individualized combinations based on previous tumor responses. Both patients died with recurrent tumor three and nine months posttransplant. The eight remaining patients were treated more uniformly with local irradiation, VM-26, doxorubicin, melphalan (L-phenylalanine mustard), and 1,000-rad total-body irradiation in three fractions. Two of these patients had cardiac dysfunction and received no doxorubicin. Three children died in the immediate posttransplant period with disseminated fungal infections. A fourth relapsed and died nine months posttransplant. As of December 1, 1983, two children who received allogeneic marrow grafts have survived in complete remission for 54 and 36 months, and two children who received autologous marrow grafts have survived in complete remission for 35 and 22 months. These results suggest that relapsed metastatic neuroblastoma can be controlled by supralethal combinations of chemotherapy and irradiation coupled with bone-marrow rescue.

Adolescent↗
PubMed1982

Acyclovir treatment of herpes zoster infections. Use in children undergoing bone marrow transplantation.

Three patients in whom herpes zoster infections developed following bone marrow transplantation were treated with acyclovir. The patients experienced pain relief within 24 hours of starting treatment. The progression of their skin lesions halted within 1, 2, and 4 days of therapy, respectively, and healed completely within two weeks of therapy. Pharmacokinetic studies indicated that acyclovir plasma concentration-time profiles approximated biexponential equations. The drug half-lives were 3.91, 3.83, and 3.40 hours, respectively. Acyclovir was not myelotoxic and may be helpful in aborting varicella-zoster virus infections in bone marrow transplant recipients.

Acyclovir↗
PubMed1978

Influence of food and fluid ingestion on aspirin bioavailability.

The influence of test meals and accompanying fluid volume on aspirin bioavailability from commercial tablets was determined following single oral doses to healthy male volunteers. Plasma aspirin and salicylate levels were determined simultaneously using a GLC end-point. Area analysis indicated that approximately 5--8% of absorbed drug entered the systemic circulation as unchanged aspirin in nonfasted subjects compared to 16--18% in fasted individuals. Food tended to reduce the appearance rate of aspirin into the circulation, resulting in lower and somewhat more sustained levels than with fasting. Plasma salicylate levels were not influenced markedly by the various treatments, although levels were higher in fasted than in nonfasted subjects during the 1st hr after dosing. After this time, fat pretreatment tended to produce higher levels than other treatments.

Adult↗
PubMed1977

Bioavailability of ampicillin and amoxicillin in fasted and nonfasted subjects.

The influence of various test meals and fluid volume on the relative bioavailability of ampicillin and amoxicillin was studied in healthy human subjects. Serum amoxicillin levels were somewhat, but not always, significantly higher than those of ampicillin from equivalent oral doses. Food ingested immediately before dosing reduced serum levels and urinary excretion of both antibiotics to a similar extent. Reduction of dosed water volume caused a marked decrease in serum amoxicillin levels in fasted subjects.

Adult↗
PubMed1977

Bioavailability of tetracycline and doxycycline in fasted and nonfasted subjects.

The influence of various test meals and fluid volumes on the relative bioavailability of commercial formulations of doxycycline hyclate and tetracycline hydrochloride was studied in healthy human volunteers. Serum levels of tetracycline were uniformly reduced by approximately 50% by all test meals, whereas serum levels of doxycycline were reduced by 20%. The reduction of tetracycline serum levels will likely be of clinical significance. The bioavailability of each drug was almost identical from an oral solution and from capsules in fasted subjects. The rate of doxycycline absorption was reduced when capsules were administered with a small volume of water, but the overall efficiency of absorption of both drugs was essentially independent of co-administered fluid volume. The use of 8-h serum data provides a reliable estimate of drug bioavailability for tetracycline and, to a lesser extent, for doxycycline.

Adult↗