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Biomedical subjects

J P Lewis

Publications and source records attributed to J P Lewis.

At least 19 recordsLinked to original sources

Impact of polydonor mixed lymphocyte culture media on quantity and quality of myeloid metaphases.

A novel mitotic stimulator of myeloid hematopoietic cells was prospectively evaluated to detect enhanced quantity and quality of metaphases from bone marrow (BM) cultures for cytogenetic analysis. This polydonor mixed lymphocyte conditioned (PMLC) media decreased the culture failure rate, improved detection of chromosomal aberrations, and reduced technologists' analysis time. The conditioned media is recommended as a highly effective culture system for normal and neoplastic cells of myeloid lineage.

Bone Marrow

Clonal remission in aplastic anemia after treatment with antithymocyte globulin.

Aplastic anemia includes a group of disorders characterized by peripheral blood pancytopenia and marrow hypocellularity. The current report describes a patient who is an apparent constitutional mosaic and presented with marrow aplasia. Using cytogenetic analysis of bone marrow, skin, and peripheral T lymphocytes, we demonstrated the clonal nature of this patient's aplastic marrow, and, in addition, identify clonal evolution. The patient was treated with antithymocyte globulin (ATG) and achieved a complete remission, with disappearance of an abnormal evolved clone. This case illustrates that clonal cytogenetic abnormalities do not preclude a response to ATG and that aplastic anemia may be a nonmalignant clonal disorder with clonal evolution.

Aged

Analysis of mosaic states in amniotic fluid using the in-situ colony technique.

Appropriate counselling and clinical management of the pregnant woman with a mosaic amniotic fluid cell karyotype are difficult. The majority of the data on mosaicism and pseudomosaicism are derived from studies employing the flask technique for the analysis of amniotic fluid cell cultures. Since the majority of laboratories now utilize the in-situ technique, such data may not be relevant when analyzing results from the in-situ colony technique. We reviewed the incidence of mosaicism in 6339 amniotic fluid samples using the in-situ technique. Data are presented on the types of aberrations and clinical outcomes. A classification of mosaicism is presented that distinguishes mosaicism of clinical importance from that which is obviously of extrafetal origin or artifactual. This approach clarifies the significance of mosaic states detected by the in-situ colony technique and provides a rational foundation for genetic counselling and for planning clinical interventions.

Amniotic Fluid

Bone marrow scintigraphy in the evaluation of acute nonlymphocytic leukemia.

The clinical usefulness of bone marrow scintigraphy in evaluating adult acute nonlymphocytic leukemia (ANLL) was assessed through 39 studies of 23 adult patients. Nineteen patients were in various stages of relapse and remission of ANLL and four patients were preleukemic. Results of scintigraphic studies were correlated with information concerning bone marrow status, therapy, and subsequent clinical response. When 99mTc-sulfur colloid was utilized, eight of 34 studies were normal, but in the majority of patients there was an abnormal distribution of bone marrow reticuloendothial activity. Three of the patients with normal studies were in complete remission at the time of the normal scan. The duration of these remissions tended to be long. In four patients, 67Ga-citrate scintigraphy showed a wide variation of bone marrow uptake despite a marked increase in bone marrow myeloblasts. There was no significant correlation between scintigraphic distribution and bone marrow morphological status nor with subsequent ability to induce a complete remission with chemotherapy. Nevertheless, these studies raise the possibility that bone marrow scintigraphy may be useful in predicting the stability of an induced complete remission in ANLL. Confirmation of this possibility must await further studies.

Acute Disease

Inhibition of erythropoiesis by plasma component(s) from sheep, goats, and rabbits.

Plasma from hypertransfused and normal sheep and experimentally induced anemic and normal goats was fractionated by ultrafiltration. Fractions obtained were assayed for erythropoiesis stimulatory factor (ESF) or erythropoiesis inhibitory factor (EIF) activity (or both) in the posthypoxic polycythemic mouse assay. The most potent sheep plasma-inhibitor fraction was found in the retentate on a membrane with a cutoff at mol wt 50,000. The most potent EIF fraction from anemic goats passed into the ultrafiltrate, but the comparable EIF from normal goats remained in the retentate on a membrane with a cutoff at mol wt 500. The yield of the most potent EIF fraction was higher from anemic goats than was the yield from normal goats. During thin-layer chromatography, EIF extracted from goat plasma fractions had the same mobility as did prostaglandin F2 alpha. Cohn rabbit plasma fraction IV-4 had an inhibitory factor, and a benzene extract of the fraction contained a component that had the same mobility as did prostaglandin F2 alpha. Cohn rabbit plasma fraction V contained a component that potentiated an erythropoietin-generating factor.

Animals

Laetrile toxicity studies in dogs.

Dogs were fed laetrile and fresh, sweet almonds under various conditions. The doses of laetrile were similar to those prescribed for patients with cancer and ranged on a basis of gram to square meter from an equivalent of the oral dose for man to five times this dose. Six of the ten dogs died of cyanide poisoning. One dog recovered, and three dogs, at the time of sacrifice, demonstrated various levels of neurologic impairment, ranging from difficulty in walking to coma. These studies demonstrate that oral laetrile is highly toxic when taken with some common table foods. We predict that there will be an increased incidence of cyanide poisoning in man as laetrile becomes more readily available.

Administration, Oral

Eradication of the intramedullary Ph1 positive cell line without accompanying improved survival in chronic myelogenous leukemia.

A patient with Ph1+ chronic myelogenous leukemia is presented who upon entering the accelerated phase of her disease developed aneuoploidy, including duplication of the Philadelphia chromosome. Intensive chemotherapy resulted in a marrow remission and reversion of the marrow karyotype to normal. Rather than entering an anticipated prolonged remission she relapsed four weeks later with return of her aneuploid clone. Postmortem examination revealed several unsuspected areas of extramedullary leukemia, perhaps serving as the source for repopulation of the marrow. If a desired goal of therapy is to eradicate the Ph1+ cell line, then we recommend that it be undertaken early in the disease when there is the least likelihood of extramedullary leukemia.

Aneuploidy

Oropharyngeal excretion of Epstein-Barr virus by patients with lymphoproliferative disorders and by recipients of renal homografts.

In an attempt to associate oropharyngeal excretion of Epstein-Barr (EB) virus with lymphoproliferative disorders other than infectious mononucleosis, we tested throat gargles collected from adult subjects for the EB virus. Nine (16%) of 55 healthy persons were positive. High EB virus-excretion rates were found among patients with active acute lymphocytic leukemia (6/6, 100%), among renal homograft recipients during the third to 12th month after transplantation (26/30, 87%), and among critically ill patients with leukemia-lymphoma (14/19, 74%). Moderately high excretion rates were found among patients with myeloma (7/16, 44%), patients with poorly differentiated lymphocytic lymphoma (5/11, 44%), critically ill patients with solid cancers (15/37, 41%), and patients with chronic myelogenous leukemia (8/21, 38%). Our data suggested that the higher than normal excretion rate is realted to the basic disease process and to the general health status but not to the duration of cancer chemotherapy.

Antineoplastic Agents

Randomized clinical trial of cystosine arabinoside and 6-thioguanine in remission induction and consolidation of adult nonlymphocytic acute leukemia.

One hundred and forty-seven adults with acute nonlymphocytic leukemia were randomized to one of two treatment regimens utilizing cytosine arabinoside and 6-thioguanine. In regimen A the drugs were administered every 12 hours until marrow cellularity was reduced by at least 50%. In regimen B the drugs were administered every 12 hours for 5 days with five to 7 days rest intervals between courses. Decisions to continue or reinstitute therapy were based solely on marrow cellularity and marrow ratings. The overall response in referee-verified cases in both groups was similar (41%); regimen B proved to be the easier protocol to administer but required greater support. Younger patients or those with an initial high hemoglobin count responded best to these drug regimens. Only 36% of our patients experienced severe marrow hypoplasia (i.e., a 75% or greater reduction in marrow cellularity) prior to complete remission, suggesting that cytosine arabinoside and 6-thioguanine in combination may selectively suppress leukemic cells while sparing normal hematopoietic elements.

Acute Disease

Patterns of exogenous and endogenous hematopoietic repopulation following radiation injury.

Patterns of hematopoietic recovery in mice given an LD50/30 radiation exposure were different from those in animals given an LD100/30 exposure and a marrow transplant sufficient to effect 50 per cent 30-day survival. Death occurred later, and recovery of some peripheral blood elements was delayed in the LD50/30 mice. Over the period of study, splenic hematopoiesis and stem cell renewal were insignificant in the LD50/30 mice yet were active in the marrow-transplanted animals. The slow recovery of erythropoiesis in the LD30/30 mice is explained in part by the lack of early splenic hematopoiesis. This effect appeared to be attributable to the splenic microenvironment which, although being suitable for growth of unirradiated hematopoietic cells, was not conducive to repair of radiated splenic hematopoietic cells.

Animals

Laetrile.

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Amygdalin

Clinical investigation of doxorubicin, daunomycin, and 6-thioguanine in normal cats.

Cats frequently develop a variety of spontaneous hemolymphatic noeplasias. Long-term remissions in the nonlymphatic leukemic cat are difficult to obtain; therefore, more successful chemotherapeutic agents are sought for disease control. The purpose in the present study is to describe the clinical investigation of 3 antineoplastic drugs given to 23 normal cats. The cats tolerated doxorubican given at the dose level of 30 mg/m2 of body surface area once every 3 weeks; daunomycin, 15 to 30 mg/m2 once every 3 weeks; and 6-thioguanine, 25 mg/m2 for 5 days every 20 to 30 days.

Alopecia