Volumetric quantification of the effect of aging and hormone replacement therapy on breast composition from digital mammograms.

OBJECTIVE: To assess the physiological changes in breast composition with aging using volumetric breast composition measurement from digital mammograms and to assess the effect of hormone replacement therapy (HRT). METHODS: A total of 764 consecutive mammograms of 208 non-HRT using women and 508 mammograms of 134 HRT-using women were analyzed using a volumetric breast composition assessment software (Quantra™, Hologic Inc.). Fibroglandular tissue volume (FTV), breast volume (BV), and percent density (PD) were measured. For statistical analysis, women were divided into a premenopausal (<46 years), a perimenopausal (46-55 years), and a postmenopausal (>55 years) age group. More detailed graphical analysis was performed using smaller age brackets. Women using HRT were compared to age-matched controls not using HRT. RESULTS: Women in the postmenopausal age group had a significantly lower FTV and PD and a significantly higher BV than women in the premenopausal age group (FTV: 77 vs. 120 cm(3), respectively; PD: 16% vs. 28%, respectively; BV 478 vs. 406 cm(3), respectively; p<0.01 for all). Median FTV was nearly stable in consecutive mammograms in the premenopausal and postmenopausal age groups, but declined at a rate of 3.9% per year in the perimenopausal period. Median PD was constant in the premenopausal and postmenopausal age groups and declined at a rate of 0.57% per year in the perimenopausal age group. BV continuously increased with age. Women using HRT throughout the study had a 5% higher PD than women not using HRT (22% vs. 17%, respectively; p<0.001). CONCLUSIONS: Accurate knowledge of normal changes in breast composition are of particular interest nowadays due to the importance of breast density for breast cancer risk evaluation. FTV and PD change significantly during the perimenopausal period but remain relatively constant before and thereafter. Median total breast volume consistently increases with age and further contributes to changes in breast density. HRT use is associated with a significantly higher PD.

Measurement of tanning dependence.

BACKGROUND: Indoor tanning has been found to be addictive. However, the most commonly used tanning dependence measures have not been well validated. OBJECTIVE: The study's purpose was to explore the psychometric characteristics of and compare the modified Cut-down, Annoyed, Guilty, Eye-opener Scale (mCAGE), modified Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition - Text Revised (mDSM-IV-TR) and Tanning Pathology Scale (TAPS) measures of tanning dependence and provide recommendations for research and practice. METHODS: This study was a cross-sectional online survey with 18- to 25-year-old female university students. The main outcome variable was tanning dependence measured by the mCAGE, mDSM-IV-TR and TAPS. RESULTS: Internal consistency of the TAPS subscales was good but was poor for the mCAGE and mDSM-IV-TR, except when their items were combined. Agreement between the mCAGE and mDSM-IV-TR was fair. Factor analysis of the TAPS confirmed the current four-factor structure. All of the tanning dependence scales were significantly correlated with one another. Likewise, most of the tanning dependence scales were significantly correlated with other measures of tanning attitudes and behaviours. However, the tolerance to tanning TAPS subscale was not significantly correlated with any measure of tanning attitudes or behaviours and had the lowest subscale internal reliability and eigenvalues. CONCLUSION: Based on the data and existing literature, we make recommendations for the continued use of tanning dependence measures. Intervention may be needed for the approximately 5% of college women who tend to be classified as tanning dependent across measures. Monitoring of individuals reporting tanning dependence symptoms is warranted.

[Ultrasound-guided perivascular axillary brachial plexus block. A simple, effective and efficient procedure]. / Ultraschallgesteuerte perivaskuläre axilläre Plexusanästhesie. Eine einfache, effektive und effiziente Methode.

BACKGROUND: The perivascular axillary plexus block is an easily applicable procedure with a low risk of complications but with a high failure rate. To improve this, the standard procedure was combined with transpectoral sonography to benefit from the advantages of ultrasound, while using a nearly unchanged puncture technique. METHOD: The technique developed by the authors is described in this article and the success rate and the time factor were determined in a sample of 86 patients. The success rates were compared to previous rates without ultrasound and to those in the literature. RESULTS AND CONCLUSIONS: The rate of complete blocks without the use of transpectoral sonography in our clinic and in the literature was approximately 72%, whereas using transpectoral ultrasound it was 96.5%. None of the 86 patients with transpectoral sonography required general anaesthesia. The onset time using transpectoral sonography was approximately 6 min. The perivascular axillary plexus block, combined with transpectoral sonography, is an effective and efficient procedure.

Postmortem blood free and total morphine concentrations in medical examiner cases.

This purpose of this study was to determine the relationships between postmortem free morphine and total morphine levels in a large series of medical examiner morphine and heroin related deaths. Free morphine, total morphine, and 6-monoacetylmorphine (6-MAM) concentrations were measured by gas chromatography-mass spectrometry (GC-MS) in 87 medical examiner cases over 20 months. The mean total morphine concentration, mean free morphine concentration, and mean percent free morphine for all cases were: 2.3 mg/L (SD 5.2 mg/L), 0.5 mg/L (SD 1.6 mg/L), and 19.4% (SD 22.8%); respectively. Regression analyses showed weak correlations between total and free morphine concentrations over the entire concentration range (0 to 36.6 m/L, r = 0.603, n = 91) and over a subset concentration range of 0 to 1.0 mg/L (r = 0.369, n = 54). Twenty-three out of 56 (41%) tested positive for 6-MAM, indicative heroin abuse cases. Lower total and free morphine concentrations and a higher percent free morphine were found in individuals with detectable 6-MAM. Comparing blood concentrations for cases with and without detectable 6-MAM demonstrated mean total morphine concentrations of 0.9 mg/L versus 2.1 mg/L (p = 0.05), mean free morphine concentrations of 0.3 mg/L versus 0.4 mg/L (p = 0.21), and mean percent free morphine of 34.7% versus 13.7% (p < 0.003), respectively. Our findings demonstrate higher free to total morphine ratios in individuals with detectable 6-MAM than in individuals without 6-MAM. The database established in this study may assist medical examiners in the evaluation of postmortem blood opiates regarding the cause of death in opiate related ingestion cases.

A computational study of the effectiveness of the frontier molecular orbital formalism in predicting conformational isomerism in (p-RC6H4NC)2W(dppe)2.

Ab initio electronic structure calculations on a series of ligands, p-RC6H4NC:, indicate, that the energy of the LUMO correlates with the electron-withdrawing/donating capabilities of the substituent group, which determines the relative pi-acidity of the ligand. Depending on the nature of the para substituent group on the aryl isocyanide ligand, bis(aryl isocyanide) complexes of tungsten-containing bulky bidentate arylphosphine ligands adopt either cis or trans conformations. The frontier molecular orbital formalism predicts that strong pi-acids, which contain electron-withdrawing groups, tend to polarize sufficient charge density away from the metal center to effect the formation of the sterically less favorable but electronically stabilized cis conformer. Density functional theory calculations on similar complexes containing phosphines which do not impose severe steric contraints indicate that the balance between steric and electronic stabilization can be effectively predicted by comparing the relative energies of the ligand LUMOs.

Evidence-based implementation of free phenytoin therapeutic drug monitoring.

BACKGROUND: The majority of laboratories measure total phenytoin concentration for therapeutic drug monitoring. However, there are substantial interindividual variations in free phenytoin concentrations, the pharmacologically active component. METHODS: We describe the process and data used to implement monitoring of free phenytoin only in an urban medical center. Over a 6-week period, total and free phenytoin concentrations were measured, clinical charts reviewed, and indications for alterations in the percentage of free phenytoin fraction were determined. RESULTS: Of the 189 phenytoin requests from 139 patients, 136 data points were analyzed. Free phenytoin concentrations were 6.8-35.3%, with 50% outside the expected range of 8-12%. Clinical indications likely responsible for variations were hypoalbuminemia, drug interactions, uremia, pregnancy, and age. Overall, 30% of patients demonstrated a discrepancy between therapeutic, subtherapeutic, or supratherapeutic concentrations between free and total phenytoin concentrations. The largest discordance (53%) occurred in the patient group with free phenytoin <8% or >12%. CONCLUSIONS: This study supports previous clinical findings that monitoring total phenytoin is not as reliable as free phenytoin as a clinical indicator for therapeutic and nontherapeutic concentrations. Thus, we recommend that therapeutic monitoring should use free phenytoin concentrations only.

Cocaine, cocaine metabolite, and ethanol concentrations in postmortem blood and vitreous humor.

The use of postmortem cocaine and metabolite concentrations is a complex subject. This study was undertaken to determine (1) the usefulness of vitreous humor as a specimen, compared with blood, to quantitate cocaine and cocaine metabolites; (2) whether there is a preferential site of disposition for cocaethylene between vitreous humor and blood; and (3) if the presence of cocaethylene influences the concentration of benzoylecgonine in postmortem specimens. Cocaine, benzoylecgonine, and cocaethylene were quantitated in blood and vitreous humor by gas chromatography-mass spectrometry, and ethanol was quantitated by gas chromatography in 62 medical examiner cases. No differences were found between mean concentrations of vitreous cocaine 0.613 mg/L (standard deviation [SD] 0.994 mg/L), cocaethylene 0.027 mg/L (SD 0.59 mg/L), and ethanol 0.092 g/dL (SD 0.13 g/dL) compared to blood cocaine 0.489 mg/L (SD 1.204 mg/L), cocaethylene 0.022 mg/L (SD 0.055 mg/L), and ethanol 0.058 g/dL (SD 0.91 g/dL), respectively. However, a statistical difference was found between mean benzoylecgonine concentrations in vitreous 0.989 mg/L (SD 1.597 mg/L) and blood 1.941 mg/L (SD 2.912 mg/L) (p = 0.0004). Regression analysis demonstrated that linear relationships were present between concentrations of vitreous and blood cocaine (r = 0.854) and benzoylecgonine (r = 0.763). However, the correlation coefficients were lower for cocaethylene (r = 0.433) and ethanol (r = 0.343). There were variations between the concentrations of cocaine and metabolites both in terms of magnitude and also direction of change. Mean concentrations of benzoylecgonine in blood and vitreous were higher in cases where ethanol was absent, 2.593 mg/L (SD 3.195 mg/L) and 1.431 mg/L (SD 2.021 mg/L), compared to when ethanol was present, 1.199 mg/L (SD 2.396 mg/L) and 0.469 mg/L (SD 0.553 mg/L). This study demonstrates that vitreous humor may be used to quantitate cocaine and cocaine metabolites; however, because the concentrations of cocaethylene in vitreous humor and blood were not well correlated, vitreous humor may not be a reliable specimen for measuring cocaine and cocaine metabolite concentrations.

Expression cloning of neurotrophic factors using Xenopus oocytes.

We have explored the potential for cloning novel neurotrophic factor cDNAs via assay of neurotrophic activities following expression in Xenopus oocytes. In this report, we describe the successful application of the method to tract rat ciliary neurotrophic factor (CNTF) activity from mRNA purified from cultured cells and from mRNA synthesized by in vitro transcription of a cDNA library. Rat C6 glioma cells, which had been previously shown to have CNTF-like activity (Westermann et al., 1988), were used as source material. We tested protein extracts of C6 cells using an in vitro assay of primary neurons from the chick ciliary ganglion (CCG assay) and detected a CNTF-like activity. RNA isolated from C6 cells was shown to direct the synthesis of the activity following microinjection into Xenopus oocytes and one-step fractionation of Xenopus extract. C6 mRNA was size-fractionated, and fractions encoding CNTF-like activity were cloned into a lambda phage vector at a site distal to a T7 promoter. Synthetic RNA transcribed from total library DNA was injected into Xenopus oocytes, and a CNTF-like activity in the oocyte extract was detected by the CCG assay. Further fractionation of library clones narrowed the presence of the clone encoding the CNTF-like activity to a pool containing 20,000 members. The presence of a full-length CNTF cDNA clone in this pool and partial clones in other pools was confirmed by Polymerase Chain Reaction (PCR) using oligonucleotides from the rabbit CNTF cDNA (Lin et al., 1989) as primers.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereospecific microbial reduction of 4,5-dihydro-4-(4-methoxyphenyl)-6-(trifluoromethyl-1H-1)-benzazepin+ ++-2-o ne.

A key intermediate, (3R-cis)-1,3,4,5-tetrahydro-3-hydroxy-4-(4-methoxyphenyl)-6-(trifluorome thyl)- 2H-1-benzazepin-2-one (compound II or SQ32191), with high optical purity was made by the stereoselective microbial reduction of the parent ketone 1. Several strains of bacterial and yeast cultures were screened for the ability to catalyse the stereoselective reduction of 4,5-dihydro-4-(4-methoxyphenyl)-6-(trifluoromethyl)-1H-1-benzazepin++ +-2,3-dione [compound I or SQ32425]. Microorganisms from the genera Nocardia, Rhodococcus, Alkaligenes, Corynebacterium, Arthrobacter, Hansenula, and Candida reduced compound I to compound II with 60-70% conversion yield. In contrast, microorganisms from the genera Pseudomonas and Acinetobacter reduced compound I stereospecifically to (trans)-1,3,4,5-tetrahydro-3-hydroxy-4-(4-methoxyphenyl)-6-(trifluoromet hyl-2H- 1-benzazepin-2-one (compound III or SQ32408). Among various cultures evaluated, N. salmonicolor SC6310 effectively catalysed the transformation of compound I to compound II with 96% conversion yield at 1.5-2.0 gl-1 concentration. Compound II was isolated and identified by NMR analysis, mass spectrometry, and comparison to an authentic sample. Preparative scale fermentation process and transformation process were developed using cell suspensions of N. salmonicolor SC6310 to catalyse the transformation of compound I to compound II. The isolated compound II had a melting point of 222 degrees C (reference 221-223 degrees C), optical rotation of +130.4 (reference +128 degrees C), and optical purity of greater than 99.9% as analyzed by NMR and chiral HPLC.

Sequence and structural organization of the human gene encoding ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) is a potent polypeptide hormone whose actions appear to be restricted to the nervous system where it promotes survival, neurotransmitter synthesis and neurite outgrowth in certain neuronal populations. We have cloned the gene encoding human CNTF (hCNTF) and have characterized its structure and organization. The hCNTF gene appears to be a unique-copy gene with a simple genetic organization, since only a single intron interrupts the coding domain. The hCNTF gene is located on chromosome 11, as determined using human-hamster somatic cell hybrids. The CNTF protein is highly conserved in evolution. The amino acid (aa) sequences of rat and rabbit CNTF translated from cDNAs display approx. 85% homology with the deduced aa sequence encoding hCNTF.

A team format for the Global Assessment Scale: reliability and validity on an inpatient unit.

The Global Assessment Scale (GAS) is a 100-point rating instrument which purports to measure psychological adjustment on a continuum from self-actualization to severe regression. Its reliability and validity were examined on the admitting ward of a state hospital where GAS ratings are assigned to patients by computing a mean of the individual ratings assigned by a team of clinicians. Results showed such team GAS ratings to have good reliability. As for validity, team GAS predicted the outcomes of court hearings at two stages of the civil commitment process and showed construct validity in its relevant correlations with the Psychotic Inpatient Profile. A predicted association between team GAS and a ward atmosphere measure was not obtained. Taken as a whole, the results support the use of team GAS ratings in inpatient settings.

Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid.

Synovial fluid from arthritic patients contains multiple forms of phospholipase A2 (PLA2), as resolved by high performance liquid chromatography (Seilhamer, J.J., Plant, S., Pruzanski, W., Schilling, J., Stefanski, E., Vadas, P., and Johnson, L. K. (1989) J. Biochem. (Tokyo), submitted for publication). Here we describe the cloning of a human 4.5-kilobase gene and 800-base pair cDNA encoding the form representing the major peak of activity and protein mass (peak A). The clones encode a mature peptide of 124 amino acids, which follows a prepeptide of 20 residues. The deduced amino acid sequence constitutes an enzyme of the "Type II" class of PLA2s, and resembles PLA2s from other mammalian sources. This represents the first report of a full length mammalian non-pancreatic PLA2 sequence. Active transcription of this PLA2 gene was detected in two different inflammatory cell sources. Recombinant human peak A PLA2 was expressed in vaccinia as a secreted protein which accumulated in conditioned medium.

Reactive perineurial fibroblastic proliferation of the median nerve: MR characteristics.

We report a case of fibroblastic proliferation of the median nerve presenting as a focal mass. This report discusses the pathological and magnetic resonance correlations and reviews the differential diagnosis for median nerve masses.

CT for determining the results of treatment of fractures of the wrist.

Eighteen CT examinations of the wrist were performed in 13 patients to evaluate the results of treatment for carpal fractures. In four cases with metal objects and in seven with cast materials, there was no difficulty achieving adequate CT studies. In 13 cases CT was found to be helpful in determining bony union in the presence of advanced osteoporosis. In six cases CT was excellent in evaluating bone-graft incorporation. CT affords improved detection of fractures perpendicular to the plane of the scan and also shows small areas of bone disruption, even with osteoporosis. Axial CT images can evaluate Lister's tubercle, a bony prominence on the dorsum of the distal radius, for hypertrophy, which can occur secondary to traumatic and degenerative changes. A hypertrophied tubercle can impinge on the extensor pollicis longus tendon and cause atrophy and disruption. The high cost of CT is offset by the possibility of reducing the patient's period of immobilization and, thereby, the length of time the patient is unable to participate in normal activities. In addition, since CT is often definitive, the number of supplemental or follow-up radiologic procedures or clinical appointments should be reduced. We conclude that CT is useful in evaluating the results of treatment of wrist injuries.

Pseudallescheria boydii arthritis and osteomyelitis in a patient with Cushing's disease.

Pseudallescheria boydii infection involving the left distal femur and knee joint developed in a patient with Cushing's disease, and recurred after treatment with both intravenous miconazole and intravenous amphotericin B. The patient subsequently had synovectomy and arthrodesis, and received ketoconazole, 600 mg per day orally for one year. Concurrent with the start of ketoconazole, a bilateral adrenalectomy was done to control endogenous hypercortisolism. The patient's infection then resolved, and one year afterward there is no clinical or radiologic evidence of recurrent infection.

The use of methylmethacrylate as a temporary spacer following en bloc resection of the distal femur.

The current state of the art of prosthetic joint replacement permits sizeable segments of the appendicular skeleton to be resected and replaced with prosthetic components which are secured with methylmethacrylate cement. Occasionally it is necessary to resect a rather sizeable area of pathologic bone and to provide for some type of temporary fixation until a specially fabricated prosthetic component can be made available. Under such circumstances it is necessary to maintain length of the involved extremity, and provide for skeletal stability to the area of resection. Although external fixation offers a reasonable option, the employment of an internal type of fixation in the form of titanium mesh reinforced with methylmethacrylate cement seems more desirable. With this technique, the potential problem of pin track infection is avoided while space suitable to the dimensions of the prosthetic implant can be preserved.