Biomedical subjects

E M Walker

Publications and source records attributed to E M Walker.

At least 109 records · Page 6Linked to original sources

PubMedDate not supplied

Prolonged ingestion of commercial DDT and PCB; effects on progesterone levels and reproduction in the mature female rat.

A report linking human polycystic ovary with increased exposure to environmental DDT (Heinrichs et al. 1971) prompted the present study comparing effects of PCB and DDT or their combination on reproduction in female rats under more realistic conditions with respect to level (75 and 150 ppm), route of administration (dietary contaminant), and period of exposure (8 and 36 weeks). Evaluation of estrous cycle length, mating frequency, number and size of litters; as well as plasma levels of DDT, PCB, progesterone (P), and 17 alpha=hydroxyprogesterone (17 alpha=OH-P), permitted comparison of short and long term reproductive changes from ingestion of two levels of DDT and/or PCB. PCB reduced plasma progesterone (p less than .01) while plasma 17alpha OH-P was unchanged by PCB or DDT. High DDT and PCB abolished reproduction. Histologically, distinct ovarian stromal changes accompanied 150 ppm of PCB, while increased numbers of more prominent follicular cysts were evident with 150 ppm of DDT. Although DDT and PCB generally reduced or abolished litter production, no treatment tested significantly altered litter size. Long term chronic ingestion of more realistic levels of technical DDT (85% p,p', 15% o,p'-DDT) in these studies did not lead to polycystic ovaries in adult rats comparable to those reported following i.v. administration of pure o,p'-DDT to immature rats. Plasma DDT levels above 800 ppb are clearly detrimental to reproduction, while levels below 500 ppb had lettle effect. Finally, we present the first evidence reported to our knowledge demonstrating that prolonged ingestion of PCB (150 ppm) markedly reduces reproduction (p less than .05) accompanied by significantly reduced progesterone in plasma (p less than .01) as well as by histologically characteristic ovarian stromal changes not seen with DDT alone.

Animals↗

PubMedDate not supplied

Genome structure of spirochetes.

The genome structures of several pathogenic spirochetes have recently been determined. The genomes of Borrelia species consist of a linear chromosome of approximately one million base pairs (Mb) and various linear and circular plasmids. Analysis of restriction fragment length polymorphisms and 16S ribosomal RNA sequence data indicate the division of Borrelia burgdorferi into at least three distinct genetic groups. Leptospira interrogans has a circular chromosome 5 Mb in size and a 0.35 Mb extrachromosomal element. Repetitive sequence elements similar to insertion sequences have been identified in the Leptospira interrogans genome. The chromosome of Treponema pallidum subsp. pallidum is circular and has a size of approximately one Mb. Genetic studies conducted to date indicate that B. burgdorferi and L. interrogans have a high degree of genetic diversity, whereas remarkably few genetic differences have been observed among the pathogenic Treponema. Knowledge of the genomic structure of these organisms will serve as a basis for future genetic studies.

Borrelia burgdorferi Group↗

PubMedDate not supplied

Tca: a high-frequency blood group antigen.

An IgG antibody defining a high-frequency red cell antigen was detected in the sera of two unrelated, nontransfused black women GT (gravida 1, para 0) and DLC (gravida 4, para 2). Inheritance of the antigen was established by the family study of DLC. The clinical significance of the antibody is not yet known. The antibody has been designated anti-Tca, and the corresponding antigen, Tca. No Tc(a-) individuals were found among 5000 Caucasians, 5000 Japanese, or 450 blacks; however, anti-Tca was identified in the sera of two other unrelated black women (LZ and WM). A relationship between Tca and Cra has been proposed by other serologists, but further evidence is needed to confirm the association.

Black People↗

PubMedDate not supplied

Treponemicidal antibody measured by the "washed-killing" assay correlates with immunity in experimental rabbit syphilis.

BACKGROUND AND OBJECTIVES: The authors have previously shown that complement-dependent treponemicidal antibody measured by the "washed-killing" assay is directed exclusively against surface-exposed targets on Treponema pallidum, presumably the Treponema pallidum rare outer membrane proteins detected by freeze-fracture electron microscopy. GOAL OF THIS STUDY: Because immune mechanisms against Treponema pallidum rare outer membrane proteins are likely to be central to a protective host response, it was examined whether a relationship could be established between treponemicidal levels as measured by the "washed-killing" assay and host immunity in experimental syphilis. STUDY DESIGN: Three groups of Treponema pallidum-infected rabbits were treated curatively with penicillin at 9 days, 30 days, and 6 months post-infection to generate animals with varying degrees of immunity to challenge re-infection. The level of complement-dependent treponemicidal activity in sera obtained before infection (basal) and before intradermal challenge was determined by the "washed-killing" assay and compared with that detected using conventional in vitro immobilization. RESULTS: Using the "washed-killing" assay, a close quantitative correlation as measured by a treponemal immobilizing endpoint titer was demonstrable between prechallenge treponemicidal antibody and the status of immunity to re-infection. Sera from rabbits completely susceptible to symptomatic and disseminated asymptomatic re-infection lacked treponemicidal antibody. Sera from challenged rabbits with a relatively low degree of immunity to symptomatic disease showed endpoints of < or = 4. Rabbits with a relatively high degree of immunity to symptomatic reinfection and resistant to disseminated disease had endpoints that ranged from 6 to 96. Rabbits completely resistant to challenge exhibited endpoints ranging from 96 to 128. CONCLUSION: Treponemicidal antibody measured by the "washed-killing" assay correlated closely with the status of immunity in experimental rabbit syphilis. Thus, antibody measured by this assay may be directed against key protective Treponema pallidum surface immunogens.

Animals↗

PubMedDate not supplied

Evolution of chemotherapy with platinum compounds.

Cancer is a major disease entity and cause of death in the human population. The discovery of cisplatin has revolutionized the chemotherapy of human cancer. The full therapeutic potential of cisplatin has not been realized due to the serious side effects and emergence of cisplatin-resistant tumor cells associated with its usage. Protective methods such as extensive hydration, improved schedules of administration, alternate routes of administration, and use of protective agents against specific side effects have allowed the use of higher doses of cisplatin against cisplatin-resistant tumors and has extended the list of tumor systems responsive to cisplatin chemotherapy. Incorporation of cisplatin into a number of cisplatin-based anti-cancer drug combinations has enhanced its effectiveness and allowed the use of lower doses of cisplatin, thus reducing its toxic side effects. Finally, the availability of cisplatin analogues, such as carboplatin and others with reduced toxicity, but increased effectiveness against cisplatin-resistant tumors, has expanded the potential scope and therapeutic promise of the platinum anti-cancer agents. The evolution of chemotherapy with the platinum antitumor compounds is ongoing.

Animals↗

PubMedDate not supplied

Fine needle aspiration in the diagnosis of liver neoplasms: a review.

Fine needle aspiration biopsy (FNAB) for the diagnosis of liver neoplasms is a safe, rapid, and accurate technique. It is most useful in patients with a hepatic mass(es) and a previously diagnosed malignant neoplasm. With the current application of immunocytochemical techniques, accurate cytologic diagnoses can be made in most primary and secondary hepatic neoplasms. The equipment necessary to perform FNAB is simple, inexpensive, and readily available. The principle of this technique is to obtain a representative cellular aspirate via a small bore needle and produce a stained image on a microscopic slide that reflects the disease process in the patients. Techniques and clinical skills of FNAB and experiences of interpretation are required to make maximal use of this diagnostic modality.

Biopsy, Needle↗

PubMedDate not supplied

Lymph node pathology of acquired immunodeficiency syndrome (AIDS).

There has been a recent notable increase in the number of patients in the United States seropositive for the human immunodeficiency virus (HIV) and also an increase in the number of otherwise healthy homosexuals with persistent generalized lymphadenopathy (PGL). Lymphoid tissue appears to be a favorite target for the initial viral infection, subsequent opportunistic infections, and associated neoplasms. Therefore, evaluation of PGL is important in understanding the nature of the disease. Biopsies of the acquired immunodeficiency syndrome (AIDS) lymph nodes show a spectrum of abnormal lymphoid proliferations, eventual lymphoid depletion, Kaposi's sarcoma, and malignant lymphoma. Although the individual features of AIDS-related lymphadenopathy may not be specific, the constellation of histologic, immunologic, ultrastructural, and fine needle aspiration findings is characteristic.

AIDS-Related Complex↗

PubMedDate not supplied

In vitro studies with dimethyldithiocarbamate, possible new antimicrobial for use in poultry.

Tests were conducted to determine the in vitro efficacy of the dithiocarbamate analogue, dimethyldithiocarbamate (DmDTC), against selected poultry pathogens. Organisms studied were two bacteria, Pasteurella multocida and Escherichia coli, and a mold, Aspergillus fumigatus. Zone of inhibition and the minimum inhibitory concentration were determined for each organism. DmDTC was effective in vitro against all organisms tested, with A. fumigatus showing greatest overall sensitivity.

Animals↗

PubMedDate not supplied

In vivo studies with dimethyldithiocarbamate, a possible new antimicrobial for use against Aspergillus fumigatus in poultry.

Dimethyldithiocarbamate (DmDTC), the carbamate analogue, was tested for therapeutic efficacy in a series of in vivo challenge trials using 5- and 10-week-old white leghorn chickens. Challenge organisms were Pasteurella multocida X-73, Escherichia coli O1:K1, and Aspergillus fumigatus. Birds were evaluated for survival rates, lesion scores, and the rate at which the bacteria or mold could be reisolated following challenge. Results showed DmDTC to be ineffective against P. multocida and E. coli at the treatment levels and in the form used in these trials, but DmDTC significantly reduced lesion scores and inhibited the rate of isolation of A. fumigatus compared with untreated infected birds.

Animals↗

PubMedDate not supplied

Combination and individual antitumor effects of hyperthermia, cisplatin, and selected dithiocarbamates.

The antitumor effects produced by combinations of cisplatin (Pt), substituted dithiocarbamates (dimethyldithiocarbamate [DmDTC] and sodium N-methyl-D-glucamine dithiocarbamate [NMGDTC]) and hyperthermia (H) were measured and compared to those produced by single agents alone in C3H/HeN mice bearing the transplantable radiation-induced fibrosarcoma, RIF-1, in one or both hind feet. The average tumor volumes of control and treatment groups were compared periodically after treatment with H. Combinations of H and Pt completely resolved established foot tumors in 10/13 mice. However, evidence of long-term nephrotoxicity and gastrointestinal (GI) toxicity became evident causing death of these mice within 120 to 122 days after tumor inoculation. Hyperthermia plus DmDTC resolved tumors in heated and non-heated feet in 3/8 mice, thus demonstrating both ipsilateral and contralateral anti-tumor activity. Furthermore, H-Pt-NMGDTC produced complete tumor resolution in 7/13 mice; these mice survived and were tumor-free 180 days post inoculation and autopsies revealed no appreciable nephro- or GI toxicity. In addition, 4/8 mice underwent complete tumor resolution in heated left feet plus dramatic retarding of tumor growth in unheated right feet (ipsilateral and contralateral anti-tumor effects). Five heat-treated left foot tumors resolved in the H-Pt-DmDTC group with one mouse demonstrating resolution of tumor in both feet. Advanced foot tumors were treated with H-DmDTC and H-Pt-DmDTC. Hyperthermia and Pt were administered on day 0 of the experiment and DmDTC on days 0 through 3; dramatic tumor shrinkage continued through day 6 for a total of 75 to 80 percent reduction of tumor volume in both groups. The concurrent administration of DmDTC or NMGDTC with H and Pt prevented or greatly reduced nephrotoxicity and GI toxicity in all experiments without retarding anti-tumor efficacy.

Animals↗

PubMedDate not supplied

In vitro antimicrobial activity of diethyldithiocarbamate and dimethyldithiocarbamate against methicillin-resistant Staphylococcus.

Staphylococcus aureus has appeared which is highly resistant to both methicillin and aminoglycosides. Current therapy involves long-term intravenous therapy of vancomycin. Since vancomycin is currently the only drug used to treat these patients, there is a need to develop additional antimicrobial therapy. The in vitro antimicrobial effect of the metal chelator, diethyldithiocarbamate (DDTC) and its structural analog dimethyldithiocarbamate (DMTC) were investigated. Both DDTC and DMTC were effective against S. aureus including methicillin-resistant S. aureus (MRSA). By agar diffusion, DDTC at 10 micrograms per disk produced zone sizes of 12 to 21 mm and at 100 micrograms per disk produced zone sizes of 26 to 34 mm against MRSA. The DMTC produced slightly greater zone sizes against MRSA of 16 to 24 mm and 24 to 37 mm for 10 micrograms per disk and 100 micrograms per disk, respectively. The minimum inhibitory concentration (MIC) for DMTC against MRSA was 6 micrograms per ml. Both DDTC and DMTC were also effective against enterococci, Proteus mirabilis, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Salmonella species, Serratia marcescens and Citrobacter freundii at 100 micrograms per disk. The MICs of DMTC for Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Salmonella and Citrobacter freundii were approximately 128 micrograms per ml while the MICs for Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa and Serratia marcescens was greater than or equal to 256 micrograms per ml. In addition, DMTC was synergistic with gentamicin against MRSA and coagulase-negative staphylococcus species, Enterobacter cloacae, Klebsiella pneumoniae and Pseudomonas aeruginosa. Additive and synergistic effects of DMTC were displayed with gentamicin against S. aureus including methicillin-resistant S. aureus.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

PubMedDate not supplied

Status of current clinical tests for human immunodeficiency virus (HIV): applications and limitations.

Two laboratory tests are currently used to detect the human immunodeficiency virus (HIV) specific antibodies that are produced when an individual has been infected by the virus at some time. These include the enzyme-linked immunosorbent assay (ELISA) as the screening test and the Western blot (WB) as the confirmatory test. They are not yet optimally effective and have brought with them some problems, especially when used to screen low risk populations such as asymptomatic blood donors. Currently licensed ELISA tests used to detect HIV have sensitivities that range between 93 percent and 99 percent, and all have specificities greater than 99 percent. An important concern is that the positive predictive value for the ELISA screening test is low in spite of the fairly high sensitivity and high specificity values. This poor predictive value is due to the low prevalence of individuals in the general population who have been infected with HIV. Multiple causes of false positive ELISA and Western blot tests have been identified. They can be eliminated by utilizing reagent antigens which are produced by recombinant deoxyribonucleic acid (DNA). The false negative ELISA and Western blot tests can be reduced by tests designed to detect IgM antibodies to HIV.

Antibodies, Viral↗

PubMedDate not supplied

Disulfiram as a radiation modifier.

The radiation modifying effect and toxicity of tetraethylthiuram disulfide (disulfiram) have been studied. Disulfiram (DSM) inhibits aldehyde dehydrogenase, dopamine-beta-oxygenase, microsomal mixed-function oxidases and cytochrome P-450 enzymes. It is widely used for aversion therapy in alcoholism. Disulfiram also inhibits tumor formation by several known carcinogens. A biphasic toxicity pattern of DSM is reported in the L-929 mouse fibroblast culture system. Disulfiram is 100 percent toxic at 2 X 10(-7) M (0.05 micrograms per ml), 23 percent toxic at 3 X 10(-7) M (0.1 microgram per ml), and 100 percent toxic again at 3.4 X 10(-6) M (1.0 microgram per ml). The pattern is similar to the biphasic toxicity pattern of DMS's major metabolite, sodium diethyldithiocarbamate (DTC). Reports of both radiation protection and radiation enhancement by DTC exist. Previously, a radioprotective effect by 2 X 10(-6) M DTC (dose modifying factor = 1.26) has been demonstrated in the L-929 cell system. To date, no radiation modifying properties of DSM have been reported. Our investigation of DSM as a radiation modifier at 3 X 10(-7) M (0.1 microgram per ml) did not show significant improvement in survival of irradiated cells treated with DSM relative to the irradiated control group, as determined by absence of a difference in the Do of the two groups. Considering DSM's close structural relationship to DTC, it is possible that DSM may exhibit a radioprotective effect when applied in a different concentration than what was used in our research.

Animals↗

PubMedDate not supplied

Effects of drugs on the male and female reproductive systems.

Infertility, permanent or temporary, resulting from drug-induced injury is an important clinical problem. Many common used drugs are potentially toxic to gonads. It is well-known that estrogens are toxic to the male genital system, but androgens may also produce infertility. Anovulation may also be a consequence of exposure to sex steroids. Cimetidine regularly produces hypospermia in men; phenytoin does so occasionally. Marijuana has been shown to be a gonadal toxin, while the effects of lysergic acid diethylamide (LSD) remain controversial. The most significant group of drugs that may injure the gonads is the cancer chemotherapeutic agents, of which the alkylating agents are the worst offenders. Prediction of infertility induced by these agents may be possible based on the duration of therapy and the patient's age and sex.

Adult↗

PubMedDate not supplied

Histochemistry of bone marrow aspirations.

The accuracy of diagnosis of hematological diseases from bone marrow aspirates and peripheral blood smears is considerably improved by use of histochemical stains. As hematopoietic cells differentiate and mature from the pluripotent stem cell and are committed to a particular cell line, the committed cell lines produce different substances, particularly enzymes, which can be identified by various histochemical stains. Histochemical stains are not diagnostic, but are aids in diagnosis, because various cell lines may produce similar substances and because the stains lack absolute specificity. A discussion of the use of histochemical stains for the diagnosis of leukemias is presented. Complete procedures for Prussian blue stain for iron, peroxidase, Sudan black B, naphthol AS-D chloroacetate esterase, nonspecific esterase, periodic acid Schiff (PAS), acid phosphatase, toluidine blue and alkaline phosphatase stains are given in the appendix.

Acid Phosphatase↗

PubMedDate not supplied

Current status of leukocyte and platelet administration in cancer therapy.

Leukapheresis and plateletpheresis are rather commonly performed in order to obtain single donor concentrates of granulocytes and platelets. These procedures, although relatively safe, present occasional risks to donors and recipients. Some of the occasional adverse problems experienced by donors include citrate toxicity or acute hypocalcemia, hypotension, hypervolemia, venospasm or vein occlusion, chills, anaphylactoid reactions, hemorrhage, abdominal pain or complications related to equipment failure and related technical problems. Potential risks to donors include those related to the receiving of six percent hydroxyethyl starch (HES), dextrans, or corticosteroids, lymphocyte depletion or immunosuppression, and effects on the complement system. Prophylactic granulocyte transfusions to prevent the occurrence of infections and associated complications in neutropenic patients have not proven to be efficacious; therapeutic granulocyte transfusions appear to be more effective. Indications for therapeutic granulocyte transfusions include those patients with known infections unresponsive to appropriately aggressive antibiotic chemotherapy over a two or three day period combined with findings of a peripheral granulocyte count less than 500 mm3 and especially those with counts below 100 mm3 and/or prolonged fever greater then 38 degrees C (100.4 degrees F) for 24 to 48 hours. In addition, the patient should have a reasonable chance for bone marrow recovery. Hazards or complications associated with granulocyte transfusions include: (a) immediate transfusion reactions, (b) hypersensitivity reactions, (c) pulmonary infiltrates, (d) alloimmunization, (e) transmission of infections, and (f) the possibility of Graft vs. Host (GVH) disease. The current best use of apheresis platelets is to provide therapeutic doses of single donor matched platelets for patients refractory to pooled random donor platelets. Alloimmunization represents the major complication of therapeutic platelet transfusion and is characterized clinically by the failure to achieve expected platelet count increments after transfusion. Future developments which might greatly improve the effectiveness of therapeutic and possibly prophylactic leukapheresis and plateletpheresis include the development of effective sedimenting agents with shorter biological half-lives, more efficient and less expensive methods of procurement of granulocytes and platelets, improved methods of cryopreservation of granulocytes and platelets, better methods for detecting and quantitating antigranulocyte and/or antiplatelet antibodies, and more efficient evaluation of possible synergism of granulocyte transfusions with antibiotic therapy and residual host defense. These improvements may be of great value in the effective utilization of granulocyte and platelet products and in determining which patients are most likely to receive the maximum benefit from granulocyte and platelet support.

Agranulocytosis↗

PubMedDate not supplied

Diethyldithiocarbamate in treatment of acute cadmium poisoning.

An insoluble complex was synthesized by the reaction of sodium diethyldithiocarbamate trihydrate (DDTC) with CdCl2 X 2.5 H2O (Cd). Elemental analyses of the product yielded a percent composition of each element which was consistent with the postulated structure of two mole equivalents of (DDTC)- and one mole equivalent of Cd++. The DDTC formed a complex with 11 other metal ions tested, but not with Ca++ or Mg++. The complex with Cd was highly insoluble in water, 0.1 N HCl, 0.1 N NaOH, human serum, and carbon tetrachloride, but it was soluble in pure dimethyl sulfoxide. The DDTC protected mice from a greater than LD100 dose of Cd. This protective effect was more pronounced when DDTC treatment was delayed at least 30 min after i.p. administration of Cd. More than 98 percent of mice treated with 500 mg per kg of DDTC 30 min to five hrs after Cd administration survived, and 50 percent survived when treatment wad delayed for eight hrs. Administration of DDTC prior to or immediately after Cd gave less protection. The lowest (DDTC)-/Cd++ molar dose ratio which resulted in 100 percent survival following the otherwise lethal dose of Cd was 7.6, which was less than four times the theoretical stoichiometric molar ratio for formation of the complex. The LD50 of the complex in mice wa approximately 650 mg per kg of the i.p. route, indicative of a low degree of dissociation in vivo.

Acute Disease↗

PubMedDate not supplied

Methods of reduction of cisplatin nephrotoxicity.

Cisplatin, an agent widely used in the chemotherapy of a variety of human malignancies, is often dose-limited owing to its nephrotoxicity. Some of the approaches under consideration, regarding the reduction of cisplatin nephrotoxicity, include the use of hydration and osmotic diuresis, pharmacological diuretics, chelating agents or agents which otherwise react with cisplatin or reverse cisplatin-induced deoxyribonucleic acid cross-links, and antioxidants to destroy free radicals, especially superoxide radicals, produced by cisplatin. The effects of each of these and other interventions on cisplatin-induced nephrotoxicity are delineated, along with their proposed mechanisms and effects on therapeutic efficacy. The current status of development of organoplatinum analogs yielding congeners with less nephrotoxicity and greater efficacy is discussed briefly. Finally, a possible role of endogenous and/or exogenous prostaglandins in protecting against or reversing heavy metal nephrotoxicity is suggested.

Amifostine↗