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Mangafodipir trisodium injection (MnDPDP) is an intravenously administered manganese chelate undergoing clinical evaluation for magnetic resonance imaging contrast enhancement of the hepatobiliary system. The anticipated single clinical dose for adults is 5 μmol/kg body wt. MnDPDP, as well as the inorganic salt, MnCl2, was previously shown to induce a specific syndrome of skeletal abnormalities in rats. The syndrome malformations included angulated or irregularly shaped clavicle, femur, fibula, humerus, ilium, radius, scapula, tibia, and/or ulna. The objective of the present study was to assess the developmental toxicity of MnDPDP in a second mammalian species, the New Zealand White rabbit. MnDPDP was intravenously administered daily to groups of rabbits (22 per group) on Days 6 through 18 of pregnancy at doses of 0 (saline), 5, 20, 40, and 60 μmol/kg MnDPDP. Fetuses were examined on Day 29 of pregnancy for external, visceral, and skeletal abnormalities. Treatment with MnDPDP did not result in overt symptoms of maternal toxicity, and there were no significant effects on maternal body weight gains or feed consumption. The maternal no-observed-adverse-effect level (NOAEL), therefore, was 60 μmol/kg MnDPDP. Treatment with MnDPDP resulted in a significant increase in postimplantation loss at 60 μmol/kg, but there was no significant increase in external, visceral, or skeletal abnormalities at any dose. The developmental NOAEL for MnDPDP, therefore, was 40 μmol/kg. These results indicate that the developmental toxicity profile of MnDPDP differs considerably in the rat and rabbit. In the rat, this compound induces specific skeletal abnormalities, whereas in the rabbit, embryo/fetal toxicity is the most sensitive developmental endpoint with no evidence for the induction of specific skeletal abnormalities.

Human health risk assessments involving contaminated soil include dermal absorption as a potential pathway contributing to the total exposure burden. For PCB-contaminated soil, the U.S. Environmental Protection Agency uses a dermal absorption factor of 14%, based on a 1993 study of dermal absorption in rhesus monkeys. The current study examined several parameters that can influence the dermal absorption of lipophilic hydrocarbons, including soil organic content, particle size, skin residence time, and contaminant "aging" in the soil. Four groups of four female rhesus monkeys each were exposed to radiolabeled Aroclor 1260 either intravenously (100% absorption) or dermally with PCB-spiked soil. Groups exposed for 12 or 24 h to PCBs aged in soil exhibited percutaneous absorption values of 3.43 +/- 0.35 and 4.26 +/- 0.52%, respectively, while a group exposed for 24 h to soil freshly spiked with PCBs exhibited a dermal absorption value of 4.07 +/- 0.46%. Evidence strongly suggests that the factor most responsible for modulating the percutaneous absorption of highly lipophilic compounds from soil is its organic content. The base soil used in the current study with Aroclor 1260 had an organic content of 5-6% (< or =2 mm particle fraction), a value typical for U.S. soil. The organic content of the soil applied to the skin was 8.7% (

The antagonistic effects of CGS-15943A on the relaxations produced by adenosine and its analogs in human blood vessels were investigated in vitro. Donor hearts were the source of coronary arteries, whereas the internal mammary arteries and saphenous veins were obtained from patients undergoing coronary bypass surgery. Adenosine and its analogs, 5′-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD), produced concentration-dependent relaxations in KCl-contracted coronary rings. CGS-15943A antagonized, significantly, the relaxations produced by adenosine, NECA and CAD in coronary arteries. Similarly, the adenosine receptor antagonist, 8-phenyltheophylline (8PT, 10-μmol/1), caused a significant attenuation of the relaxing responses to adenosine, NECA and CAD in coronary arteries. In rings obtained from internal mammary arteries and saphenous veins, adenosine, NECA and CAD all produced concentration-dependent relaxations. These relaxations were smaller in magnitude than those obtained in coronary arteries, and were slightly greater in rings contracted with 10 μmol/1 prostaglandin F 2α (PGF 2α ) as compared to 35 mmol/1 KCl. However, the mammary arteries and saphenous veins relaxed completely in response to 100 μmol/1 papaverine. CGS-15943A (10 μmol/1) did not antagonize the relaxing effects of adenosine and its analogs in these vessels. The results show that coronary arteries are more responsive than mammary arteries or saphenous veins to the relaxing effects of adenosine analogs and that these relaxing responses are dependent on the contracting agent. Furthermore, CGS-15943A demonstrated antagonism of the adenosine response in coronary arteries.

The neonatal and obstetric approaches to preventing group B streptococcal neonatal infections are reviewed. Although recent reports recommend prophylactic antibiotic treatment of antepartum and intrapartum group B streptococcal carriers and low-birth-weight infants, acceptance of these schemes is not widespread. A preliminary study to evaluate the value of semiquantitative vaginal and cervical cultures of antepartum women for group B streptococcus in predicting maternal and neonatal infectious morbidity revealed: 1) 11% of the study population were carriers (group B streptococcus isolated from broth only) but only 2.8% had heavy colonization (growth in broth and on streaked plates), and 2) morbidity associated with 8 heavily colonized mothers during the current pregnancy included group B streptococcal endometritis (1 patient), neonatal sepsis (1), and readmission of a newborn for transient cyanosis (1). Two of the heavily colonized mothers were known carriers in their last pregnancy; 1 had group B streptococcal endometritis and the infant of the second developed clinical sepsis at 2 weeks of age. The clinical value of semiquantitative culture techniques requires additional investigation.

Patients with allergic rhinitis receiving maintenance inhalant immunotherapy and two control groups were studied for evidence of circulating immune complexes. The first control group contained patients with allergic rhinitis who had never received immunotherapy. The second control group contained normal volunteers. Patients in the treatment group had no proteinuria. When compared with the control group, the treatment group had no statistically significant differences in incidence of Clq binding immune complexes, cryoglobulinemia, rheumatoid factor, or complement depletion. This initial study suggests that maintenance immunotherapy does not result in an increase of circulating immune complexes.

The response to preseasonal immunotherapy with aqueous grass extract, timothy antigen D, or water-soluble timothy (WST) in alginate was compared in patients sensitive to grass pollen. Injections of antigen D in alginate produced little evidence of clinical or immunologic response. Treatment with aqueous grass extract or WST in alginate, on the other hand, significantly reduced the seasonal rise in grass-specific IgE. Aqueous extract therapy was also associated with a decline in leukocyte sensitivity during the pollen season, while WST treatment produced the greatest rise in hemagglutinating antibodies.

Forty patients with various types of myeloproliferative disorders were evaluated immunologically. Serum immunoglobulin levels were within the normal range in most patients and no monoclonal gammopathies were detected. Serum C'3 levels were decreased in 19 of 40 (48%) patients. The response of peripheral blood lymphocytes to phytohemagglutinin was decreased in 26 of 40 (65%) and to pokeweed mitogen in 18 of 28 (64%) patients studied. Lymphocytes from patients with polycythemia vera were least affected. Unstimulated lymphocytes from some patients demonstrated markedly increased thymidine uptake activity. Despite the diminished mitogenic response, only 2 of 33 patients (6%) were anergic by intradermal skin testing. There was no association between depressed lymphocyte response and recent chemotherapy except in chronic myelogenous leukemia where 6 of 8 patients were receiving cytotoxic therapy when studied. These observations suggest that most of our patients with myeloproliferative disorders have abnormal cellular responses in vitro, but that delayed hypersensitivity and humoral responses are minimally affected.

A randomized controlled investigation was undertaken to evaluate the role of maternal oral antibiotic therapy in decreasing the incidence of maternal and neonatal colonization at term with group B beta-hemolytic streptococcus (GB-BHS). Data were collected to determine the optimum transfer media and the colonization rate in the study population. At delivery 1441 maternal-infant pairs were evaluated. One hundred sixty-eight women (11.6%) and 55 infants (3.8%) were colonized. Forty-four women colonized with GB-BHS at 38 weeks' gestation were randomly assigned to a treatment (500 mg potassium penicillin or erythromycin ethylsuccinate q.i.d.) or a control group to determine the value of antepartum oral antibiotic therapy in preventing infant colonization. There was a significant reduction in maternal (P = 0.008) and infant (P = 0.004) colonization rates in the treatment group. There were no observed complications of antibiotic therapy in mothers or infants. This study suggests that routine cultures for GB-BHS should be done at 38 weeks' gestation. Mothers colonized at this time may be considered candidates for prophylactic antibiotic treatment.

Polymer emulsions will undergo film formation upon loss of water if the driving force provided by capillary pressure is sufficient to overcome the resistance of the polymer particles to deformation. The conditions for film formation are expressible in terms of the surface tension and particle size of the dispersion, the time available for the drying process, the temperature, and the rheological properties of the polymer.

Torsional modulus–temperature data have been obtained on heterogeneous polymer compositions prepared by several procedures. Both the state of aggregation of the component chain molecules and their degree of compatibility are significant variables. Modulus curves similar to those for crystalline polymers can be obtained from incompatible polymers having glass temperatures sufficiently far apart. Detailed interpretations are presented for modulus curves of both individual homopolymers and bicomponent heterogeneous polymer mixtures.

Military personnel returning from Vietnam were evaluated serologically for melioidosis, using the hemagglutination test (HA). A total of 500 serum samples were studied. Titers greater than or equal to 1:80, observed when test erythrocytes were sensitized with polysaccharide antigen extracted from Pseudomonas pseudomallei, were recorded as diagnostic. In the wounded patient group, six (three per cent) had diagnostic titers. One serum specimen from the medically-ill group and one from the US control group had diagnostic titers. Antibody activity in all positive serum samples (i.e. diagnostic titer) was mercapto-ethanol (2-ME) resistant. The primary and the secondary immune responses of rabbits immunized with killed P. pseudomallei cells were serologically evaluated with the hemagglutination test; appropriate erythrocyte suspensions were sensitized with polysaccharide or protein component extracted from peudomallei cells. Results of this study are discussed.

An apparatus has been constructed for measurement of the minimum filming temperature (MFT) of a polymer emulsion. The apparatus consists of a metal bar along which a temperature gradient may be maintained. Recessed channels are provided in which emulsion samples are spread and allowed to dry. Eight thermocouple stations along the bar are connected to a continuous recorder. Following drying of the film, the minimum temperature at which a continuous film is formed is determined. Testing of the apparatus on one emulsion examined under a variety of conditions and on samples of varying composition has demonstrated the reliability, versatility, and utility of the apparatus.

The isolation of two graft copolymers of styrene on polyethyl acrylate from the ungrafted homopolymers by solvent extraction procedures is discussed. For the grafts and their corresponding mixtures ηsp/c versus c plots were determined, and no anomalies were observed. Qualitative data on the solubilities and phase properties of the grafts are given. Torsional modulus-temperature curves are shown for graft copolymer and the individual homopolymers.

Latex thickening—the process of increasing the viscosity of a polymer emulsion by addition of a water-soluble polymer —has been studied by rheological measurements and by the examination of other colloidal properties. For the systems studied, which represent a range of polymers in both the dispersion and solution phases, the flow curves were represented over a wide range of shear rate by the equation, S = K(τ − τ0)2, where S is shear stress, τ is shear rate, and K and τ0 are constants, of which the latter is considered to be a yield stress. Aside from the generality of the mathematical function, the behavior of various latex-thickener pairs is extremely specific to the pair involved. Additional data on latex creaming and on the influence of the thickener and latex concentrations confirms the specificity. The available data indicate that latex thickening is not simply an enhancement of the viscosity of the aqueous phase by the thickener, but that in addition to this the ability of the thickener to flocculate or deflocculate the latex is an important part of the mechanism of thickening. These colloidal interactions change, often precipitously, with minor changes in the polymers, the latex emulsifier, and the concentrations of the components.

Antibody formation in high-altitude-acclimatized and nonacclimatized rabbits was investigated at altitudes of 14,100 (Pikes Peak, Colo.) and 5,330 (Denver, Colo.). Serum pools representing samplings of primary response were titered before and after treatment with 2-mercaptoethanol. Peak titers of 2-mercaptoethanolresistant and -sensitive humoral antibodies were higher in the animals adapted to an altitude of 14,100 ft and in nonadapted animals than in animals maintained at 5,330 ft.

Immunoglobulin M hemagglutinin and antibody cytophilic for macrophages were produced simultaneously in mice after primary antigenic stimulation with sheep erythrocytes in saline. Antigen emulsified in Freund's complete adjuvant induced formation of cytophilic antibody (CA) in high titer. Purified cytophilic globulin was isolated by permitting it to attach to macrophages in vitro and eluting it at 56 C. The chromatographic elution pattern, molecular weight, and resistance to mercaptoethanol suggested that CA is a member of the immunoglobulin G class of immunoglobulins.

The use of incubators in the care and support of premature babies has received attention since Martin Cooney, a student of Pierre Budin, began showing premature infants in incubators at the 1896 Berlin Exposition. 1 As early as 1907, Budin 2 observed increased survival in low birth weight infants if they were kept warm. This effect of the thermal environment was not fully appreciated until Silverman and co-workers 3-5 demonstrated increased survival in warmer environments in a series of studies first published in 1958. Since the first edition of Standards and Recommendations for Hospital Care of Newborn Infants , 6 the use of incubators has been suggested for thermal support and isolation. In 1969, Du and Oliver 7 demonstrated the effectiveness of a radiant warmer in protecting against the cold stress of the delivery room. The increased access to the infant during resuscitation has led to increased use of radiant warmers

We compared in-vitro mitogen induced lymphoproliferative response (IVMILR) between paired samples of colostral lymphocytes (CL) and blood lymphocytes (BL) using equal numbers of T-cells or a T-cell subpopulation. Standard lymphocyte counting, sheep erythrocyte rosetting (SER), “active” sheep erythrocyte rosetting (ASER) and IVMILR techniques were used. Optimal mitogen concentration was established by dose response curves. Cultures had 95% viability by trypan blue staining. Morning colostrum and blood was donated at 3 days postpartum by 18-35 year old primiparous Caucasians with normal pregnancy & delivery. Twelve samples were evaluated for % of SER and ASER cells: BL had 60% SER and 40% ASER cells, CL had 30% SER and 20% ASER cells. Six samples of 95% SER cells and 3 of 95% ASER cells were evaluated for IVMILR after isolation over Ficoll-Hypaque. BL SER cells had stimulation index (SI) 2-10 times greater than CL SER cells. BL ASER cells had SI 2-5 times greater than CL ASER cells. Three samples of CL and BL were co-cultured and IVMILR revealed no change in slope of dose response curve. IVMILR of CL T-cells was hyporeactive when compared to equal numbers of matched BL T-cells. The IVMILR of CL “active” T-cells, a subpopulation of T-cells, was hyporeactive when compared with an equal number of matched BL “active” T-cells. There is no evidence of suppressor cell or substance produced by milk cells. The CL T-cell is different than the BL T-cell.