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Biomedical subjects

G Schwartz

Publications and source records attributed to G Schwartz.

At least 19 recordsLinked to original sources
PubMed1992

Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer.

High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous marrow support, time to engraftment, antibiotic days, transfusion requirements, and lengths of hospital stay were all significantly improved for the patients receiving PBPCs. Thus, autologous PBPCs can be efficiently collected during mobilization by chemotherapy and GM-CSF and are an attractive alternative to marrow for hematopoietic support after high-dose therapy. The enhanced speed of recovery may reduce the morbidity, mortality, and cost of high-dose treatment. Furthermore, PBPC support may enhance the effectiveness of high-dose therapy by facilitating multiple courses of therapy.

Adolescent↗
PubMed1992

A defective splice site at the phenylalanine hydroxylase gene in phenylketonuria and benign hyperphenylalaninemia among Palestinian Arabs.

Phenylketonuria (PKU) and benign hyperphenylalaninemia (HPA) result from different combinations of mutations at the locus for phenylalanine hydroxylase (PAH). While some of these mutations show widespread ethnic distribution, others are unique to specific communities. We report here the first point mutation common among Palestinian Arabs. The mutation (IVS2nt1) involves a dinucleotide substitution (Gg-->Aa) at the donor splice site of intron 2 of the PAH gene and abolishes a recognition site of the restriction enzyme MnlI. IVS2nt1 is associated with two PAH polymorphic haplotypes, 7 and 42. Homozygotes for this mutation are affected with severe, classical PKU. Compound heterozygotes carrying the IVS2nt1 allele and one of several other yet unknown mutations show different degrees of benign HPA.

Base Sequence↗
PubMed1992

Serum and mononuclear cell potassium, magnesium, sodium and calcium in pregnancy and labour and their relation to uterine muscle contraction.

Thirty women in their third trimester of pregnancy (37-42 weeks), 40 women during and 72 h after labour and 18 non-pregnant controls were studied for changes in serum and mononuclear cell cation content, and their relationship to cervical effacement and intensity of pain as measured by plasma beta endorphin concentrations during labour. Serum magnesium fell from 0.95 +/- 0.01 (mean +/- SEM) to 0.84 +/- 0.02 mmol/litre at late pregnancy and further to 0.76 +/- 0.01 during labour (P < 0.001); serum potassium fell from 4.25 +/- 0.05 to 3.79 +/- 0.06 mmol/litre (P < 0.0001) during labour; and serum calcium fell from 2.40 +/- 0.02 to 2.28 +/- 0.01 mmol/litre at late pregnancy (P < 0.001) and further to 2.25 +/- 0.02 mmol/litre during labour (P < 0.001). Mononuclear cell magnesium content rose from 4.5 +/- 0.3 to 5.6 +/- 0.04 fmol/cell (P < 0.02); potassium content rose from 37.7 +/- 2.0 to 50.9 +/- 3.0 fmol/cell (P < 0.001); and calcium content rose from 4.4 +/- 0.4 to 7.6 +/- 1.1 fmol/cell (P < 0.105). On the other hand, mononuclear cell sodium content fell from 7.2 +/- 0.5 to 3.8 +/- 0.3 fmol/cell (P < 0.001). Plasma beta endorphin concentrations increased with increasing degrees of effacement, as did intracellular Na, whereas intracellular Mg and K showed an inverse trend. A significant correlation was found between intracellular cation and beta endorphin levels (r = -0.98, Mg; -0.99, K; 0.83, Na). These changes are probably due either to intercompartmental cation shifts or possibly to endometrial ischaemia and damage during labour.

Adolescent↗
PubMed1991

Combined chemical and mechanical effects on free radicals in UHMWPE joints during implantation.

An electron spin resonance (ESR) technique is employed to determine the free radical distribution in the articulating surfaces of retrieved acetabular cups and knee-joint plateaus (retrieved after more than 6 years of implantation). Similar measurements made on samples prepared from cyclically stressed and unstressed cups, and on samples following oxidations in nitric acid and intralipid solutions provided sufficient data to gain more knowledge about the combined chemical and mechanical effects on PE free radicals during implantation. In UHMWPE free radicals are primarily initiated by gamma-ray sterilization; however, during implantation, peroxy (scission type) free radicals are formed and reach a maximum concentration level (equilibrium state) due to oxidation by chemical (hemoglobin and/or synovial fluids) environment of the joints. Subsequently, due to frictional heating and stress in the loading zones, free radical reaction is accelerated and their number is reduced only in those areas. This is consistent with the observations of a temperature rise in acetabular cups during in vitro frictional wear stress tests and in vivo telemetry observations, as reported by others. Compared with the previously reported SEM micrographs the low-free-radical regions are correlated with high-wear areas and the high-free-radical regions with the low-wear areas.

Biocompatible Materials↗
PubMed1991

GM-CSF potentiated peripheral blood progenitor cell (PBPC) collection with or without bone marrow as hematologic support of high-dose chemotherapy: two protocols.

High-dose chemotherapy with autologous bone marrow support (ABMS) achieves prolonged relapse-free survival in relapsed lymphomas and leukemias and has provided durable complete responses in certain solid tumors. The principal morbidity and mortality result from the infectious and bleeding complications during the 3-4 week aplasia until the bone marrow autograft can recover. Hematopoietic growth factors, alone or used after chemotherapy, increase the number of circulating progenitor cells in the peripheral blood compartment. In one trial, 12 patients with solid tumors were treated with high-dose chemotherapy and supported with both bone marrow and peripheral blood progenitor cells (PBPC) collected after GM-CSF administration. Reconstitution of bone marrow function occurred quickly (ANC greater than 500/microliters by day 17; platelet-transfusion independence by day 16), resulting in short hospital stays (median, 28 days). In a second study, 12 patients with metastatic breast cancer responding to induction chemotherapy (doxorubicin, 5-fluorouracil, and methotrexate) were given GM-CSF during induction to collect PBPCs during leukocyte recovery. These PBPCs were used as the sole hematopoietic support during high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin. Granulocyte and platelet reconstitution were extremely rapid (median, 14 and 12 days, respectively). When compared with 29 patients undergoing the same intensification therapy using ABMT as sole support, time to hematopoietic recovery, transfusion requirements, and duration of hospital stay were all significantly improved for the patients receiving PBPC. PBPC with or without marrow may enhance the safety, tolerance, and cost of high-dose therapy. Moreover, PBPC may render multiple course combination, high-dose therapy feasible.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

The rise of serum creatinine levels during labor.

Serum creatinine, blood urea nitrogen and creatine phosphokinase were measured in 32 women during the last 3 weeks of pregnancy and, in a further 39 women, during and after labor. The serum creatinine increased from 61.9 +/- 0.9 to 69.8 +/- 1.8 mumol/l (mean +/- SEM) (P less than 0.05) in the third stage of labor and returned to normal by 72 h after delivery. The muscle creatine phosphokinase increased from 54 +/- 7 to 77 +/- 9.9 units (P less than 0.05) during the third stage and remained high (87 +/- 13.3 units) 72 h later. We conclude that these changes are due to muscle contraction and injury during delivery.

Adolescent↗
PubMed1991

Muscarinic acetylcholine receptor-mediated phosphoinositide turnover in cultured human retinal pigment epithelium cells.

Cultured retinal pigment epithelium cells prepared from post-mortem adult human eyes are shown to contain muscarinic receptors associated with phosphoinositide turnover. Carbachol at a concentration of 100 microM induced a four-fold increase in 3H-inositol phosphates (more than 76% is in the form of 3H-inositol-1-phosphate) accumulation within 45 min in cells prelabelled with 3H-myoinositol and exposed to 5 mM LiCl. The EC50 of carbachol was approx. 70 microM and the saturation concentration was about 1 mM. The carbachol-induced response was blocked by both atropine and pirenzepine, the former being most effective. Pre-exposure of cells to carbachol resulted in desensitization and a drastic reduction in the subsequent carbachol-induced stimulation of 3H-inositol phosphates. The carbachol response could be attenuated by the biologically active phorbol ester, 4 beta-phorbol 12-myristate 13-acetate, and this was nullified by the protein kinase C inhibitor, staurosporine. The biologically inactive phorbol ester, 4 alpha-phorbol 12,13 dideconoate, did not attenuate the carbachol-induced stimulation of 3H-inositol phosphates. Pertussis toxin failed to influence the carbachol receptor-mediated phosphoinositide turnover. These studies provide clear evidence for the occurrence of muscarinic receptors coupled to phosphoinositide hydrolysis on human retinal pigment epithelium cells.

Adult↗
PubMed1991

Bromocriptine in the treatment of alcohol dependence.

A double-blind controlled study of the effects of bromocriptine on drinking behavior and associated symptoms in ambulatory alcoholics showed a marked improvement in both treatment and control groups. However, significant differences in favor of the medication were observed in psychopathological measures, and trends in the same direction in most of the other efficacy parameters.

Adult↗
PubMed1991

Serum and intracellular electrolytes in patients with and without pain.

The effect of acute stress, with and without pain, on serum and mononuclear cell cation content was studied in 205 healthy women in their last trimester of pregnancy or during normal labour, in patients with acute medical conditions in which pain was or was not present, in acute surgical conditions, and immediately prior to elective surgery. In all subjects there was a fall in serum sodium, potassium, magnesium and calcium concentrations during stress, with an apparent shift into the intracellular space. An inverse correlation was present between the severity of pain and the fall in serum cations.

Adolescent↗
PubMed1991

Compound heterozygosity in nonphenylketonuria hyperphenylalanemia: the contribution of mutations for classical phenylketonuria.

Hyperphenylalaninemia (HPA) results from defective hydroxylation of phenylalanine in the liver, in most cases because of defective phenylalanine hydroxylase. HPA is highly variable, ranging from moderate elevation of plasma phenylalanine with no clinical consequences to a severe disease, classical phenylketonuria (PKU). Non-PKU HPA was found in excess of PKU in Israel, while the opposite is true in Europe. To study the genetic basis of non-PKU HPA, we performed haplotype analysis at the phenylalanine hydroxylase locus in 27 families with non-PKU HPA. All individuals with this condition were compound heterozygotes. In six of these families, in which both PKU and non-PKU HPA were segregating, haplotype analysis showed that non-PKU HPA resulted from compound heterozygosity for a PKU mutation and a second mutation, with milder effect, which is probably expressed only when it interacts with the severe mutation. The involvement of PKU mutations in non-PKU HPA was further demonstrated in Jewish Yemenite families with non-PKU HPA, in which the individuals with this condition were carriers of the single PKU allele which exists in this community. In addition, two previously known PKU point mutations (R261Q and R408W) were found in individuals with non-PKU HPA. These mutations are associated, in our population, with the same haplotypes as those with which it is associated in Europe. Based on the above-mentioned genetic model for non-PKU HPA, successful prenatal diagnosis of this condition was performed in one family.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

A routine method for the measurement of the sodium, potassium, magnesium and calcium content of human lymphocytes.

We describe a rapid, single-step procedure for the isolation of human lymphocytes from whole blood, suitable for a routine clinical laboratory. Lymphocyte content of sodium, potassium, magnesium and calcium were measured simultaneously in a group of controls and found to fall within expected ranges. Expression of results per mg protein produced less inter-individual variation than per unit cell. In order to examine another, physiologically different but normal population, women during pregnancy were also studied. The cation content of lymphocytes expressed per mg protein was significantly lower than for controls due to a 44% increase in protein content per cell.

Adult↗
PubMed1990

A single origin of phenylketonuria in Yemenite Jews.

Phenylketonuria (PKU) is a metabolic disease caused by recessive mutations of the gene encoding the hepatic enzyme phenylalanine hydroxylase (PAH). The incidence of PKU varies widely across different geographic areas, and is highest (about 1 in 5,000 live births) in Ireland and western Scotland, and among Yemenite Jews. A limited number of point mutations account for most of the PKU cases in the European population. Here we report that a single molecular defect--a deletion spanning the third exon of the PAH gene--is responsible for all the PKU cases among the Yemenite Jews. Examination of a random sample of Yemenite Jews using a molecular probe that detects the carriers of this deletion indicated a high frequency of the defective gene in this community. Although the deleted PAH gene was traced to 25 different locations throughout Yemen, family histories and official documents of the Yemenite Jewish community showed that the common ancestor of all the carriers of this genetic defect lived in San'a, the capital of Yemen, before the eighteenth century.

Alleles↗
PubMed1990

The relationship between beta-endorphin levels and uterine muscle contractions during labor.

Plasma beta-endorphin (BE) levels (8.6 +/- 0.8 pmol/l) (mean +/- SE) were lower in the third trimester than in non-pregnant controls (14.8 +/- 1.1 pmol/l) (P less than 0.001), increased during labor, to 29.3 +/- 4.4 pmol/l (P less than 0.005) and decreased, 72 h after delivery, to 3.5 +/- 0.4 pmol/l (P less than 0.001). BE levels were found to correlate significantly with uterine muscle contraction (r = 0.966, P less than 0.05) and with cervical effacement (r = 0.974, P less than 0.05) during labor.

Adult↗
PubMed1990

Late clinical testing of cognition enhancers: demonstration of efficacy.

The major difference between clinical trials for efficacy and Phase I trials is their duration; clinical trials of cognition enhancers, for example in senile dementia, require at least 6 months. Because no widely accepted treatment is available, the methodology for these trials is still in a the process of refinement. Double blind placebo-controlled trials are considered to be mandatory particularly by the FDA. Parallel group designs seem preferable and the so-called "enriched design" seems to possess advantages over more classical procedures. Outcome measures should include ratings by clinicians and family members. Self-reports are considered to be unreliable in Alzheimer patients but may be less problematic in AAMI. Psychometric tests of cognition and motor skill should also be included. An essential and pragmatic outcome criterion is, however, the quality of daily life.

Aging↗