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Winter profile of plasma sex steroid levels in free-living male western diamond-backed rattlesnakes, Crotalus atrox (Serpentes: Viperidae).

Recent field studies on the reproductive ecology of western diamond-backed rattlesnakes (Crotalus atrox) from populations in southern Arizona showed significant differences in the concentration of plasma sex steroids (testosterone, T; 5alpha-dihydrotestosterone, DHT; and 17beta-estradiol, E2) throughout the active season (March-October), and peak levels were coincident with the two mating periods (late summer and early spring). There is, however, no information on levels of sex steroids during winter. Similar to most snakes, hibernating individuals of C. atrox are typically inaccessible, but in southern Arizona, where environmental conditions are typically mild during winter, adult males frequently bask at or near the entrances of communal dens. Basking activity, therefore, offers a unique logistical opportunity to assess the complete annual profile of plasma sex steroid levels in males of a temperate reptile in nature. From November to February, we measured levels of plasma T, DHT, and E2 in adult male C. atrox that were located basking at communal dens. Additionally, cloacal, core body, and ambient air temperatures were obtained to investigate potential relationships between body temperatures and levels of sex steroids. Mean levels of T, DHT, and E2 were relatively high, and the concentration hierarchy was T>DHT>E2. Mean levels of T, DHT, and E2 showed no significant variation across the four months of sampling; however, E2 levels decreased progressively. In the annul cycle, sex steroid levels during winter were not basal when compared to values obtained during the active season. Mean cloacal temperatures of basking males were significantly higher than core body temperatures of non-basking males (inside dens) from November-December, and in February, which suggests that one function of winter basking is to elevate body temperatures. Steroid levels, nonetheless, were not significantly correlated with cloacal temperatures. We suggest that future field studies of male C. atrox should: (a) investigate sex steroid levels in non-basking individuals and (b) test whether elevated levels of sex steroids during winter facilitate the large increases that occur in early spring, which are coincident with the second mating season. Our findings on the reproductive biology of C. atrox and other viperids are discussed in the context of the associated-dissociated model of reproduction.

Animals↗

Comparison of the Diamond-Forrester method and a new score to estimate the pretest probability of coronary disease before exercise testing.

OBJECTIVE: We compared the Diamond-Forrester (DF) tabular method to assess pretest probability of coronary artery disease to a new scoring method (NS). METHODS: We evaluated 544 patients with suspected coronary disease who underwent both exercise electrocardiography and coronary angiography. The prevalence of any coronary artery disease (CAD) (>/=1 vessel with a >/=50% stenosis) within low, intermediate, and high pretest probability groups defined by the 2 methods was compared. The DF method used age, sex, and symptoms. The NS used those 3 factors plus 7 other risk factors. RESULTS: Overall prevalence of CAD was 41%. We compared the respective prevalence of CAD within pretest probability groups. Low probability: DF 27% versus NS 17% (P <.03); intermediate probability: DF 42% versus NS 47%; high probability: DF 70% versus NS 72%. We evaluated results separately in men and women. In women, no significant differences were found. However, in men, a significant difference in the low probability group was found (DF 47% versus NS 22%; P <.03). When the 47 asymptomatic patients were removed from the analysis, there were no differences between the 2 methods. Men: low probability, DF 17% versus NS 21%; intermediate probability, DF 45% versus NS 49%; high probability, DF 67% versus NS 72%. Women: low probability, DF 17% versus NS 15%; intermediate probability, DF 38% versus NS 27%; high probability, DF 83% versus NS 70%. CONCLUSION: In symptomatic patients, the accuracy of the 2 methods was the same. In asymptomatic patients, further evaluation in larger populations will be needed.

Coronary Angiography↗

A consecutive series (1982-1985) of radial keratotomies performed with the diamond blade.

The refractive and visual results of a consecutive series of diamond knife radial keratotomy procedures were evaluated at one year after surgery as part of an ongoing prospective study of radial keratotomy. Of the 972 procedures performed, 656 eyes (67.5%) were examined one year or more after surgery. The average amount of preoperative myopia was 4.4 diopters with a range of 0.6 to 11.9 diopters; 638 (97%) of the eyes had a preoperative uncorrected visual acuity of 20/100 or worse. The mean change in spherical equivalent after one year was 4.5 diopters. One year after surgery, 496 (76%) of the eyes were within 1 diopter of emmetropia; 310 (47%) had uncorrected distance visual acuity of 20/20 or better, 579 (88%) were 20/40 or better, and all but one eye had uncorrected visual acuity improved by at least two Snellen lines. Evaluation of refractive and visual results at the final available examination of those eyes not examined one year after surgery showed that 256 (81%) of the eyes were within 1 diopter of emmetropia; 176 (56%) had uncorrected distance visual acuity of 20/20 or better, and 287 (91%) were 20/40 or better.

Adolescent↗

X-ray-sensitivity of lymphocytes of aplastic- and Diamond-Blackfan-anemia patients as detected by conventional cytogenetic and chromosome painting techniques.

Frequencies of spontaneously occurring and X-ray induced, stable and unstable types of chromosome aberrations in peripheral blood lymphocytes from two groups of radiosensitive patients, i.e., aplastic anemia (AA) and Diamond-Blackfan anemia (DBA), were determined. Two types of staining methods, i.e., chromosome painting with two cocktails of chromosome-specific DNA libraries (Nos. 1, 3, X and Nos. 2, 4 and 8), as well as conventional Giemsa staining, were employed. Chromosome painting was done with single and multicolor fluorescence in situ hybridization (FISH). The frequencies of spontaneously occurring chromosome aberrations in AA and DBA patients were not significantly different from healthy individuals. Hypersensitivity to X-rays was seen both in G0 as well as in G2 phase of the cell cycle in lymphocytes from AA and DBA patients, confirming our earlier findings using micronucleus (DBA) and G2 radiosensitivity (AA) assays.

Anemia, Aplastic↗

Central pontine myelinolysis in a child with the Shwachman-Diamond syndrome.

The first case of central pontine myelinolysis in a child with the Shwachman-Diamond syndrome is reported. Marked fluctuation of serum glucose and sodium levels, but no hyponatremia, was observed throughout the patient's hospital course. Both of these abnormalities may have contributed to the development of the lesion. Liver abnormalities, implicated in other pediatric cases of central pontine myelinolysis, were also observed.

Anemia↗

Molecular IDDM epidemiology: international studies. WHO DiaMond Molecular Epidemiology Sub-Project Group.

The WHO DiaMond Molecular Epidemiology Sub-Project is testing the hypothesis that the geographic differences in IDDM incidence reflect population variation in the frequency of IDDM susceptibility genes (i.e., DQA1 and DQB1 alleles with sequences coding for arginine (R) in position 52 of the DQ alpha-chain, and an amino acid other than aspartic acid (ND) in position 57 of the DQ beta-chain, respectively) using a standardized case-control design. Data from twelve populations which have completed (or have nearly completed) recruitment and HLA molecular analyses are presented. There was an approximate 2-fold increase in the frequencies of DGA1*0301, DQB1*0201 and DQB11*0302 among IDDM cases compared to non-diabetic controls in most populations. Interestingly, DQA*0301 was more common in low versus moderate-high incidence countries. DQB1*0201 and DQB1*0302 were more prevalent in the moderate-high incidence areas. DQA1*R and DQB1*ND were both consistent markers of IDDM risk, with stronger associations in moderate-high versus low incidence areas. In general, individuals homozygous for both DQA1*R and DQB1*ND had the highest genotype-specific IDDM incidence rates, which approximated risk estimates for first degree relatives in several countries. These data revealed considerable variation in the frequencies of DQB1 and DQA1 alleles across countries, which likely contribute to the global patterns of IDDM incidence.

Alleles↗

Molecular epidemiology of IDDM in the Western Pacific Rim Region. WHO DiaMond Molecular Epidemiology Sub-Project Group.

HLA-DQA11 and DQB1 alleles coding for arginine (R) in position 52, and an amino acid other than aspartic acid (ND) in position 57, respectively, are strong genetic markers for IDDM in Caucasians. However, their contribution to the occurrence of the disease in Asian populations is less clear. As part of the WHO DiaMond Molecular Epidemiology Sub-Project, HLA-DQ molecular typing was performed for IDDM cases and non-diabetic controls from three populations in the Western Pacific Rim Region where incidence rates have been established (Hokkaido, Japan; Seoul, Korea; Auckland, New Zealand). DQA1*R homozygosity was significantly associated with IDDM in all areas. DQB1*ND homozygosity was also related to IDDM in Korea and New Zealand, but not in Japan. Individuals who were homozygous for DQA1*R and DQB1*ND were at highest IDDM risk in Korea and New Zealand, with the most striking findings in Auckland. In Japan, individuals carrying two DQA1*R, but only one DQB1*ND allele, were most likely to develop IDDM. These data revealed considerable genetic heterogeneity between Japan and Korea and suggest that DQA1*R and DQB1*ND alleles may explain a larger proportion of IDDM incidence in Caucasian compared to Asian populations.

Alleles↗

Shwachman-Diamond syndrome in a Mexican family.

Shwachman-Diamond Syndrome (SDS) is an inherited condition with multisystemic abnormalities including pancreatic exocrine dysfunction, neutropenia, short stature, and skeletal abnormalities. In this report, we describe the case of a 14-year-old female with a history of neutropenia, pancreatic exocrine insufficiency and pancreatic endocrine sufficiency, pancreatic lipomatosis (10), and the development of myeloid leukemia. Postmortem examination revealed a high probability of SDS. We also describe the clinical findings in the patient's six siblings, suggesting this as a familial form of SDS. Because the gene(s) responsible for this syndrome have not yet been identified, genetic confirmation is not yet possible. This is the first report in the literature of a Mexican family with probable SDS.

Abnormalities, Multiple↗

Survival after withdrawal of dofetilide in patients with congestive heart failure and a short baseline QTc interval; a follow-up on the Diamond-CHF QT substudy.

BACKGROUND: We have previously observed dofetilide to be associated with improved survival when the pre-treatment baseline QTc interval was below 429 ms. In this study we tested the natural extension of this observation-that the same group of patients should have a loss of survival benefit after withdrawal of dofetilide. METHODS: Patients with congestive heart failure (CHF) and reduced left ventricular function enrolled in the Diamond-CHF (Danish Investigations of Arrhythmia and Mortality on Dofetilide-CHF) study were eligible for our QT substudy provided they were in sinus rhythm and had a measurable QTc interval from a 12-lead standard ECG taken before randomization to placebo or dofetilide. An extended follow-up was performed from study closure, December 1996 until August 2001. RESULTS: Of the 418 patients entering the extended follow-up, 215 (51%) patients died during this 4.5 years of additional observation time. The baseline QTc interval made no prognostic difference to mortality in placebo treated patients. For dofetilide treated patients with a baseline QTc interval <429 ms, increased mortality was observed during the extended follow-up compared to placebo (risk ratio 1.5, 95% confidence interval 1.1-2.8)[corrected]. CONCLUSIONS: This follow-up study shows significant loss of survival benefit upon withdrawal of dofetilide in patients with CHF and a pre-treatment QTc interval below 429 ms. An independent randomized trial is warranted to validate these results.

Adult↗

Clonal evolution in marrows of patients with Shwachman-Diamond syndrome: a prospective 5-year follow-up study.

OBJECTIVES: Shwachman-Diamond syndrome (SDS) is characterized by varying degrees of marrow failure. Retrospective studies suggested a high propensity for malignant myeloid transformation into myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The study's aims were to determine the cellular and molecular characteristics as well as the clinical course of malignant myeloid transformation and clonal marrow disease in patients with SDS. METHODS: This is a longitudinal prospective study of 14 patients recruited for annual hematological evaluations. Results of baseline and serial hematological assessments for up to 5 years are reported. RESULTS: Clonal marrow cytogenetic abnormalities (CMCA) were detected in 4 patients (29%) on first testing or at follow-up. The abnormalities were del(20q) in two patients, i(7q) in one, and combined del(20q) and i(7q) in one. The following tests did not distinguish patients with CMCA from other SDS patients: severity of peripheral cytopenia, fetal hemoglobin levels, percentage of marrow CD34+ cells, colony growth from marrow CD34+ cells, cluster-to-colony ratio, marrow stromal function, percentage of marrow apoptosis cells, and granulocyte colony-stimulating factor receptor expression. RAS and p53 mutation analysis and AML blast colony assays were uniformly negative. No patients showed progression into more advanced stages of MDS or into AML. In one patient, the abnormal clone became undetectable after 2 years of follow-up. CONCLUSIONS: We conclude that although CMCA in SDS is high, progression into advanced stages of MDS or to overt AML may be slow and difficult to predict. Treatment should be cautious since some abnormal clones can regress.

Acute Disease↗

Long-term bone marrow cultures in Diamond-Blackfan anemia reveal a defect of both granulomacrophage and erythroid progenitors.

The hematopoietic defect of Diamond-Blackfan anemia (DBA) results in selective failure of erythropoiesis. Thus far, it is not known whether this defect originates from an intrinsic impediment of hematopoietic progenitors to move forward along the erythroid pathway or to the impaired capacity of the bone marrow (BM) microenvironment to support proliferation and differentiation of hematopoietic cells. Reduced longevity of long-term bone marrow cultures, the most physiologic in vitro system to study the interactions of hematopoietic progenitors and hematopoietic microenvironment, is consistent with a defect of an early hematopoietic progenitor in DBA. However, stromal adherent layers from DBA patients generated in a long-term culture system, the in vitro counterpart of BM microenvironment, did not show evidence of any morphologic, phenotypic, or functional abnormality. Our major finding was an impaired capacity of enriched CD34+ BM cell fraction from DBA patients, cultured in the presence of normal BM stromal cells, to proliferate and differentiate along the erythroid pathway. A similar impairment was observed in some DBA patients along the granulomacrophage pathway. Our result points to an intrinsic defect of a hematopoietic progenitor with bilineage potential that is earlier than previously suspected as a relevant pathogenetic mechanism of the disease. The finding of impaired granulopoiesis in some DBA patients underlines the heterogeneity of this rare disorder.

Adolescent↗

Microfabrication and characterization of gated amorphous diamond-based field emission electron sources.

Gated field emission electron sources of amorphous diamond (a-D) coated Si tips and a-D diodes on a rough Si substrate were studied, detailing the deposition and characterization of the thin film, the fabrication processes and the emission behavior of the electron sources. Mechanisms responsible for the emission process of the a-D coated devices are proposed. A comparison of the field emission performance of the two types of devices is presented. In addition, future improvements of the a-D diode on a rough Si cathode are discussed.

Journal Article↗

Resonant field emission through amorphous diamond thin films (a model study).

A model for field emission through an amorphous diamond thin film with defects is constructed. Theoretical study shows that the emission is enhanced by attractive defects which would make the resonant emission observable for films with thickness of about 10nm. The emitted current density in typical parameters is calculated as functions of thickness, field strength and defect density. The energy distribution of emitted electrons is attained.

Journal Article↗

Field electron emission and nanostructural correlations for diamond and related materials.

Results are presented on a complex study of field electron emission (FEE) and structural correlations for nanocrystalline diamond and nitride films. It was found that all the samples studied showed similar dependences of the Fowler-Nordheim work function and effective emitting area on the threshold emission field. Besides it was generally observed that FEE occurred at nanosized regions on the boundary of high and low conducting areas, and peaks of the emission intensity were associated with a lowered surface electron potential. Based on the experimental data, the following mechanism of low-FEE from the materials studied can be supposed. Electrons are transferred from the conducting channel into a vacuum through the low-dimensional region where the emission probability is high due to the quantum well effect. A physical model of the electron escape from a quantum well was analyzed. As follows from the estimations, the quantum size effect, being combined with a moderate field enhancement (the field enhancement factor beta=10-100), allows us to explain the observed variation in the energetic parameters for the samples studied. The function of the insulating grains is mainly to support the conducting channels in the sample body. Also, the grains can fulfill an additional function of the heat sink.

Journal Article↗

Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a rare, congenital, hypoplastic anemia that usually presents in early infancy. Congenital anomalies, particularly of the head and upper limbs, are present in about a quarter of reported patients. The disease is characterized by a moderate-to-severe macrocytic anemia, occasional neutropenia or thrombocytosis, a normocellular bone marrow with erythroid hypoplasia, and an increased risk of developing leukemia. The pathogenesis is unknown. The majority of patients respond to prednisone, and often erythropoiesis can be maintained with low doses of the drug. Both remissions and increased resistance to steroid treatment can occur. Nonresponders usually are transfusion dependent, although responses to high dose steroid, androgen, and interleukin-3 have been observed. Bone marrow transplantation can be curative.

Fanconi Anemia↗

Cryo-fracturing and cryo-planing for in-lens cryo-SEM, using a newly designed diamond knife.

High-pressure frozen rat pancreas tissue samples were cryo-fractured and cryo-sectioned with a diamond knife in the microtome of a freeze-etching device. The bulk fracture faces and block faces were investigated in the frozen-hydrated state by use of a cryo-stage in an in-lens SEM. With this combination, relevant biological structures can be investigated with a few nanometers resolution in a near lifelike state, preventing the artifacts of conventional fixation techniques. Compared to TEM replica techniques, the presented method is more versatile since no replica cleaning is necessary. Additional structures can be made visible by controlled sublimation of ice, leading to a better understanding of the three-dimensional organization of organelles, such as the endoplasmic reticulum.

Animals↗

Diamond optically transparent electrodes: demonstration of concept with ferri/ferrocyanide and methyl viologen.

A new type of optically transparent electrode is reported on--an electrically conductive diamond thin film. The electrode was free-standing (0.38 mm thick and 8 mm in diameter), mechanically polished to a 7-nm rms roughness over a 10-microm linear distance, boron-doped (0.05% B/C in the reactant gas mixture), and mounted in a thinlayer transmission cell. The electrode has a short-wavelength cutoff of approximately 225 nm, which is the indirect band gap of the material, and transmits light out to at least 1,000 nm. In theory, the electrode has an optical window from 225 nm well out into the far-infrared, except for the boron acceptor band and the intrinsic multiphonon absorptions. The electrode was used to electrooxidize ferrocyanide to ferricyanide, and the absorbance change associated with the formation of the oxidized product (lambdamax = 420 nm) was spectroscopically monitored. The electrode was also used to electroreduce methyl viologen (MV2+) to the cation radical (MV+*) and the neutral (MV0). The depletion of MV2+ (lambdamax = 257 nm) and formation of MV+* (lambdama = 398 and 605 nm) were spectroscopically monitored.

Journal Article↗

Direct analysis of oxidizing agents in aqueous solution with attenuated total reflectance mid-infrared spectroscopy and diamond-like carbon protected waveguides.

A novel approach for the direct detection of oxidizing agents in aqueous solution is presented using diamond-like carbon (DLC) protected waveguides in combination with attenuated total reflectance (ATR) mid-infrared spectroscopy. Pulsed laser deposition was applied to produce high-quality DLC thin films on ZnSe ATR crystals with thicknesses of a few 100 nm. Scanning electron microscopy and X-ray photoelectron spectroscopy has been used to investigate the surface properties of the DLC films including the sp(3)/sp(2) hybridization ratio of the carbon bonds. Beside excellent adhesion of the DLC coatings to ZnSe crystals, these films show high chemical stability against strongly oxidizing agents. IR microscopy was utilized to compare differences in the chemical surface modification of bare and protected ATR waveguides when exposed to hydrogen peroxide, peracetic acid, and peroxydisulfuric acid. The feasibility of DLC protected waveguides for real-time concentration monitoring of these oxidizing agents was demonstrated by measuring calibration sets in a concentration range of 0.2-10%. Additionally, principal component regression has been applied to analyze multicomponent mixtures of hydrogen peroxide, acetic acid, and peracetic acid in aqueous solution. Due to high chemical stability and accurate monitoring capabilities, DLC protected waveguides represent a novel approach for directly detecting oxidizing agents in aqueous solution with promising potential for industrial process analysis.

Journal Article↗