Oligonucleotide fingerprinting of isolates of Candida species other than C. albicans and of atypical Candida species from human immunodeficiency virus-positive and AIDS patients.

Oligonucleotide fingerprinting of genomic DNA from oral isolates of four different Candida species other than C. albicans and atypical chlamydospore-positive isolates from human immunodeficiency virus (HIV)-positive individuals and AIDS patients was investigated as a means for differentiating between isolates within individual species. Oligonucleotides composed of simple repetitive sequence motifs, including (GACA)4, (GATA)4, (GGAT)4, (GTG)5, and (GT)8, all yielded fingerprints suitable for strain segregation of 8 C. tropicalis isolates, 12 Torulopsis (Candida) glabrata isolates, 8 atypical Candida isolates, and, except for (GATA)4, 2 C. krusei probe in turn and so generate several distinct DNA fingerprints of the same DNA sample. However, none of the probes yielded fingerprints suitable for strain segregation with three C. parapsilosis isolates. The (GATA)4 probe was also used to detect restriction fragment length polymorphisms among a genetically closely related group of atypical Candida isolates on primary isolation from an additional HIV-infected patient. These chlamydospore-positive atypical Candida isolates were sucrose positive, were of C. albicans serotype A, hybridized weakly with the C. albicans-specific mid-repeat sequence probe 27A, and yielded fingerprint profiles by random polymorphic DNA analysis that were distinct from those derived from C. albicans isolates. The C. stellatoidea ex-type strain NCPF 3108 was indistinguishable from the atypical Candida isolates in all these tests and also yielded an identical carbohydrate and nitrogen source assimilation profile by using the ID 32C yeast identification system.     

Correlation of plasmids with infectivity of Borrelia burgdorferi sensu stricto type strain B31.

The correlation of plasmid profiles with infectivity was investigated by using five clones of Borrelia burgdorferi sensu stricto strain B31 (ATCC 35210). Plasmid profiles were determined by pulsed-field and two-dimensional gel electrophoresis. The 50% infectious dose (ID50) in hamsters was determined. The ID50 of the clone that possessed a full complement of eight linear and three circular plasmids was 10(3) cells. The loss of the 27.5- and 40-kb linear plasmids did not decrease the infectivity of these cells. Rather, the loss of the 27.5-kb linear plasmid was associated with a more disseminated infection. A moderate decrease of the ID50 from 10(3) to 10(5) cells correlated with the loss of the 9.0-kb circular plasmid and the 27.5-kb linear plasmid. A major loss of infectivity (ID50 > 10(3) cells) occurred with cells that lost the 24.7- and 27.5-kb linear plasmids and the 9.0-kb circular plasmid. A 3.0-kb HindIII fragment of the 24.7-kb linear plasmid was used as a probe to determine the presence of the homologous sequences in the three genospecies of Lyme disease spirochetes. An analysis of 21 infectious strains of B. burgdorferi sensu stricto, B. garinii, and B. afzelii revealed a consistent association of infectivity with strains possessing a linear plasmid (size range, 24 to 36 kb) that hybridized with the HindIII fragment. Western immunoblotting with hamster antisera against infectious B31 clone C-3 revealed two proteins with molecular masses of 28 and 43 kDa that were absent in the noninfectious B31 clone C-1. Additionally, a 14-kDa protein was absent in C-1 but present in infectious clone C-9 as shown by two-dimensional polyacrylamide gel electrophoresis.     

Use of hybridot assay to screen for BK and JC polyomaviruses in non-immunosuppressed patients.

Urine samples from 50 patients attending a genitourinary outpatient clinic and from 13 renal allograft recipients were investigated for evidence of infection with human BK and JC polyomaviruses using cytology and a new DNA hybridot assay. Forty four per cent of samples from the renal allograft recipients were positive by cytology and 75% by DNA hybridisation, indicating that hybridot assay is more sensitive than cytological screening. BK and JC viral DNA was found in 20% of the patients attending the genitourinary clinic, showing infection with BK virus and JC virus in a group of patients with clinical conditions not normally associated with immunological deficiency-a finding that has not been reported before.     

Terminal-Phase Chronic Myelogenous Leukemia: Approaches to Treatment

The prognosis of patients with CML has improved little in the past 50 years. The relatively benign chronic phase invariably deteriorates to a refractory and rapidly fatal terminal phase. This terminal stage has been found to have two major subtypes as defined by morphologic, cytochemical, immunologic, and enzymatic criteria--myeloblastoid and lymphoblastoid. Aggressive combination chemotherapy has achieved minimal improvement in survival once the terminal phase has begun, perhaps because only Ph1-positive stem cells remain to repopulate the marrow at this stage. Bone marrow transplantation has also been unsuccessful as therapy for the terminal phase, possibly because the patients are too debilitated to tolerate transplantation once the terminal phase has begun. Combination chemotherapy has been applied in an effort to eliminate the Ph1 chromosome-containing clone during the chronic phase. This goal has not yet been consistently achieved. Chemotherapy has also not been able to delay the onset of the terminal phase nor to prolong survival. Even in those patients in whom the Ph1 chromosome-containing clone has been eliminated, relapse to the chronic phase with return of the Ph1 chromosome has generally occurred within a brief period of time. Bone marrow transplantation during the chronic phase may hold the promise of true cure for CML, with permanent elimination of the malignant clone. However, the chronic phase can be unpredictably long and patients in the chronic phase often have few, if any symptoms. Therefore, there has been a reluctance to employ drastic therapy during the chronic phase. Techniques to predict the transformation to the terminal phase prior to overt morphologic or clinical conversion are now being developed. It may be possible in the future to attempt HLA-matched sibling donor bone marrow transplantation at the earliest signs of transformation from the chronic to the terminal phase. In this manner, optimal survival might be achieved by allowing patients to be maintained in the chronic phase for as long as possible prior to the initiation of aggressive therapy. Until this is routinely possible, continued research designed to improve the therapy of the terminal phase must be pursued. These attempts are likely to include the development and evaluation of new chemotherapeutic agents, novel methods of administration of existing drugs to better exploit their pharmacokinetics (for example, continuous infusion), and the utilization of newly described treatment approaches (such as the use of "differentiating" agents in an attempt to prevent progression to blastic transformation).(ABSTRACT TRUNCATED AT 400 WORDS)     

Factors affecting ventricular volumes determined by a count-based equilibrium method

Using a 99mTc-filled source ("ventricle") in an elliptical torso phantom, we analyzed the effect of source depth, region of interest (ROI) size, background concentration and source shape on volumes determined by an attenuation-corrected count-based equilibrium method. The calculated volume of a 96 cc sphere decreased linearly from 103 to 82 cc with increasing depth from 4 to 18 cm [vol = -1.48 X depth (cm) + 109, r = 0.99]. The calculated volume of the same sphere imaged at a depth of 9 cm increased from 98 to 117 cc with ROI sizes increasing from 161 to 1,369 pixels (1 pixel = 0.17 cm2). With increasing background concentration from 0-2 microCi/ml calculated volumes decreased from 95 to 85 cc (vol = -5.3 X background concentration (microCi/ml) + 95, r = 0.97). However, with correction for over-subtraction of background, increasing background activity caused no decrease in calculated volume (mean = 95 cc, s.d. = 1). Calculated volumes for the sphere and various cylinders were accurate, while those for cones were up to 37% lower for actual volumes ranging from 56-608 cc. This study demonstrates that multiple factors produce variability in count-based determination of phantom volumes. A careful consideration of the interaction of these factors with the edge-detection and computational algorithms is required.     

Further assessment of the effects of occupational radiation exposure in the United Kingdom Atomic Energy Authority mortality study

The United Kingdom Atomic Energy Authority mortality study was designed to investigate the relation between exposure to ionising radiation and mortality among the authority's employees. The present paper describes some of the problems encountered in assessing occupational exposure to low dose radiation and examines whether the study's conclusions about the relation between exposure and mortality could be affected by the methods used. The study covered the years 1946 to 1979 during which time the frequency with which personal film dosimeters were issued changed from weekly to monthly, and the threshold level below which measurements were not made decreased 20-fold. Exposure from "below threshold" readings made an important contribution to total exposure in the early years. Estimates, based on the remeasurement of a sample of old films, indicated that the average whole body exposure before 1961 may have been about double that which was measured. Furthermore, although records were kept of when dosimeters were lost or damaged, the associated exposures were unknown and could only be estimated. Workers whose dosimeter readings were missing for more than 5% of the time during which they were monitored had higher all cause mortality (p = 0.04) and higher mortality from accidents and violence (p = 0.05) than other radiation workers. The results of analyses of mortality in relation to whole body exposure were compared when the exposures included estimates of the below threshold and missing exposures and when these exposures were assumed to be zero. Some of the findings differed, but none changed sufficiently to alter the general conclusions. Although the trend in mortality from all cancers changed from one in which the increase with exposure was far from statistically significant (p = 0.3) when the below threshold and missing values were assumed to be zero to one that approached significance (p = 0.06) after they were estimated, calculations of the annual excess deaths from cancer per unit dose resulted in broadly similar estimates. Studies of workers exposed to ionising radiation usually focus on mortality in relation to whole body exposure. In the present paper its relation to neutron and surface exposure is also examined. Workers with measured neutron exposures had significantly lower all cause mortality than other workers with a radiation record (p = 0.03). Surface exposure was significantly related to mortality from all cancers (p = 0.02) and prostatic cancer (p less than 0.001). Some data on cancer registration are presented but these cannot be readily interpreted because cancer registration details were available only for ex-employees who may not be typical of the workforce as a whole.     

Effects of characteristic x-rays on assay of I-123 by dose calibrator

Large differences in dose-calibrator readings are obtained if "high-purity" I-123 is assayed in different containers. Large correction factors are necessary for assaying another isotope of iodine, I-125, in a dose calibrator, because of absorption of the low-energy (28.4-keV, weighted mean) emissions. We found that up to 70% of the dose-calibrator response to I-123 can be due to characteristic x-rays with energies exactly the same as those emitted by I-125, and that dose-calibrator response to I-123 is also strongly affected by the absorption properties of the vial. An appropriate method to define I-123 activity uses a gamma camera with a medium-energy collimator to establish correction factors for dose-calibrator assay of I-123 in different containers. Correction factors for a plastic syringe and a thick-wall glass vial, were determined using this method. Measurement of I-123 activity in a copper absorber will eliminate the response to x-rays, and the gamma camera is useful in establishing the necessary correction factors.     

Effect of genetic background on the therapeutic effects of dehydroepiandrosterone (DHEA) in diabetes-obesity mutants and in aged normal mice

Dehydroepiandrosterone (DHEA) was fed at 0.1-0.4% in the diet to genetically diabetic (db/db) or obese (ob/ob) C57BL/KsJ (BL/Ks) or C57BL/6J (BL/6) mice. Treatment of BL/Ks-db/db or ob/ob mice with 0.4% DHEA prevented hyperglycemia, islet atrophy, and severe diabetes associated with this inbred background, but did not affect weight gain and food consumption. Homozygous obese (ob) or diabetes (db) mice on the BL/6 background were more sensitive to DHEA, and the mild, transient hyperglycemia associated with ob or db gene expression on the BL/6 inbred background could be prevented by 0.1% DHEA. Both body weight and food consumption were decreased in BL/6 mutants maintained on 0.1% DHEA whereas this effect was not seen in BL/Ks mutants fed up to 0.4% DHEA. Early therapy with 0.4% DHEA, initiated at 2 wk of age, prevented the development of most diabetes symptoms and decreased the rate of weight gain in pups of all genotypes. In addition to therapeutic effects on both obese mutants, DHEA effected significant changes in an aging study using normal BL/6 female mice. Four weeks of DHEA treatment initiated at 2 yr of age improved glucose tolerance and at the same time reduced plasma insulin to a "younger" level. This suggests that DHEA may act in insulin-resistant mutant mice and in aging normal mice to increase the sensitivity to insulin.     

Gestational Women’s Perceptions About the Harms of Cigarette and E-Cigarette Use During Pregnancy

Objectives

The purpose of this study was to examine differences between perceived harm of cigarette and electronic cigarette (e-cigarette) use while pregnant and differences between healthcare providers’ communication about these products during pregnancy.

Methods

A convenience sample of gestational women (n?=?218; ages 18–45) living in the US completed an online survey between May and December 2017. Participants reported perceived likelihood of adverse health outcomes (e.g., low birth weight, sudden infant death syndrome) among infants/children born to mothers who used cigarettes/e-cigarettes. T-tests and two-way ANOVAs examined differences between risk perceptions of using cigarettes/e-cigarettes while pregnant based on pregnancy status (previously pregnant, currently pregnant, future pregnant). Chi-square analyses examined differences between healthcare provider communication about cigarette/e-cigarette use during pregnancy.

Results

Overall, participants believed adverse health outcomes were significantly more likely to be caused by maternal use of cigarettes than e-cigarettes. Participants who planned to be pregnant reported higher endorsement that smoking combustible cigarettes would cause a miscarriage (p?<?.05) or increased blood pressure (p?<?.05) for a child than currently pregnant participants. Participants reported healthcare providers asked about (p?<?.05), advised them not to use (p?<?.001), and talked to them about health effects of smoking combustible cigarettes while pregnant (p?<?.001) significantly more than e-cigarettes.

Conclusions for Practice

Healthcare providers working with pregnant women should perform the 5As behavioral intervention method to provide pregnant women with tobacco cessation care. They should also discuss the absolute harm nicotine exposure (via cigarettes or e-cigarettes) can have on fetal health and development.