Terahertz spectroscopy of anisotropic materials using beams with rotatable polarization.

We introduce a polarization-resolved terahertz time-domain spectrometer with a broadband (0.3-2.5 THz), rotatable THz polarization state, and which exhibits minimal change in the electric field amplitude and polarization state upon rotation. This was achieved by rotating an interdigitated photoconductive emitter, and by detecting the orthogonal components of the generated THz pulse via electro-optic sampling. The high precision (<0.1°) and accuracy (<1.0°) of this approach is beneficial for the study of anisotropic materials without rotating the sample, which can be impractical, for instance for samples held in a cryostat. The versatility of this method was demonstrated by studying the anisotropic THz optical properties of uniaxial and biaxial oxide crystals. For uniaxial ZnO and LaAlO3, which have minimal THz absorption across the measurement bandwidth, the orientations of the eigenmodes of propagation were conveniently identified as the orientation angles that produced a transmitted THz pulse with zero ellipticity, and the birefringence was quantified. In CuO, a multiferroic with improper ferroelectricity, the anisotropic THz absorption created by an electromagnon was investigated, mapping its selection rule precisely. For this biaxial crystal, which has phonon and electromagnon absorption, the polarization eigenvectors exhibited chromatic dispersion, as a result of the monoclinic crystal structure and the frequency-dependent complex refractive index.

Colossal Terahertz Magnetoresistance at Room Temperature in Epitaxial La0.7Sr0.3MnO3 Nanocomposites and Single-Phase Thin Films.

Colossal magnetoresistance (CMR) is demonstrated at terahertz (THz) frequencies by using terahertz time-domain magnetospectroscopy to examine vertically aligned nanocomposites (VANs) and planar thin films of La0.7Sr0.3MnO3. At the Curie temperature (room temperature), the THz conductivity of the VAN was dramatically enhanced by over 2 orders of magnitude under the application of a magnetic field with a non-Drude THz conductivity that increased with frequency. The direct current (dc) CMR of the VAN is controlled by extrinsic magnetotransport mechanisms such as spin-polarized tunneling between nanograins. In contrast, we find that THz CMR is dominated by intrinsic, intragrain transport: the mean free path was smaller than the nanocolumn size, and the planar thin-film exhibited similar THz CMR to the VAN. Surprisingly, the observed colossal THz magnetoresistance suggests that the magnetoresistance can be large for alternating current motion on nanometer length scales, even when the magnetoresistance is negligible on the macroscopic length scales probed by dc transport. This suggests that colossal magnetoresistance at THz frequencies may find use in nanoelectronics and in THz optical components controlled by magnetic fields. The VAN can be scaled in thickness while retaining a high structural quality and offers a larger THz CMR at room temperature than the planar film.

The pharmacokinetics of DPH after the administration of a single intravenous or intramuscular dose in healthy dogs.

The objective of this study was to determine the pharmacokinetics of diphenhydramine (DPH) in healthy dogs following a single i.v. or i.m. dose. Dogs were randomly allocated in two treatment groups and received DPH at 1 mg/kg, i.v., or 2 mg/kg, i.m. Blood samples were collected serially over 24 h. Plasma concentrations of DPH were determined by high-performance liquid chromatography, and noncompartmental pharmacokinetic analysis was performed with the commercially available software. Cardio-respiratory parameters, rectal temperature and effects on behaviour, such as sedation or excitement, were recorded. Diphenhydramine Clarea , Vdarea and T1/2 were 20.7 ± 2.9 mL/kg/min, 7.6 ± 0.7 L/kg and 4.2 ± 0.5 h for the i.v. route, respectively, and Clarea /F, Vdarea /F and T1/2 20.8 ± 2.7 mL/kg/min, 12.3 ± 1.2 L/kg and 6.8 ± 0.7 h for the i.m. route, respectively. Bioavailability was 88% after i.m. administration. No significant differences were found in physiological parameters between groups or within dogs of the same group, and values remained within normal limits. No adverse effects or changes in mental status were observed after the administration of DPH. Both routes of administration resulted in DPH plasma concentrations which exceeded levels considered therapeutic in humans.

Tachypnea and antipyresis in febrile horses after sedation with alpha-agonists.

BACKGROUND: Signs of tachypnea after sedation of febrile horses with alpha2-agonists have been noted previously but have not been further investigated. OBJECTIVES: To examine the effects of xylazine and detomidine on respiratory rate and rectal temperature in febrile horses and to investigate if either drug would be less likely than the other to cause changes in these variables. ANIMALS: Nine febrile horses and 9 healthy horses were included in the study. METHODS: Horses were randomly assigned to sedation with xylazine 0.5 mg/kg or detomidine 0.01 mg/kg. Heart rate and respiratory rate were recorded before sedation and at 1, 3, and 5 minutes after injection. Hourly measurements of rectal temperature were performed starting before sedation. RESULTS: All febrile horses experienced an episode of tachypnea and antipyresis after sedation. Rectal temperature in the febrile group was significantly lower at 1, 2, and 3 hours after sedation. In several measurements, the decrease was >1 degrees C. Respiratory rate in the febrile group was significantly increased after sedation. All febrile horses were breathing>40 breaths/min and 3 horses>100 breaths/min 5 minutes after sedation. No differences were noted between the 2 treatments. No significant changes in respiratory rate or temperature were noted in the reference group. CONCLUSIONS AND CLINICAL IMPORTANCE: Febrile horses can become tachypneic after sedation with detomidine or xylazine. The antipyretic properties of alpha2-agonists need consideration when evaluating patients that have been sedated several hours before examination.

A pilot study to assess the viability of a randomised controlled trial of methods of supplementary feeding of breast-fed pre-term babies.

OBJECTIVES: to compare the impact of two methods of supplementary feeding of pre-term babies (bottle vs cup) on subsequent breast feeding and to assess the feasibility of using a randomised controlled trial (RCT) to investigate the topic. DESIGN AND METHOD: small scale prospective RCT. Data on breast feeding, as defined as the exclusive method of feeding, were collected. A range of relevant bio-data was also collected and their impact on breast feeding assessed. SETTING: a special care baby unit in a District General Hospital in the UK. PARTICIPANTS: over a three-month period, all pre-term babies (32-37 weeks' gestation) who fulfilled the inclusion criteria and has been born to mothers who had expressed a pre-partum desire to breast feed, who had consented to take part, were included (n=14). PROCEDURE: the eligible babies were randomly allocated to supplementary feeding of breast milk, via either a cup or a bottle. Whether or not the baby was being breast fed at discharge was noted. FINDINGS: the study suggested that this RCT framework is a viable method of investigating baby feeding. Because of the small-scale nature of the project, the actual database must be treated with extreme caution. No significant differences were found between the two groups in terms of breast feeding. However, the mothers reported high levels of support and also the breast-feeding rates were above the national averages. These two findings could have contributed to the non-significant results observed in this analysis. CONCLUSIONS: if the present findings could be supported by further research, then the non-significant results relating method of supplementary feeds to subsequent breast feeding could be explained by reference to three factors. Firstly, there is, in fact, no real effect of method of supplementary feeding and subsequent breast feeding; secondly, the method adopted differed from existing research and thus may be expected to produce non-corroborative results; and finally, the overall levels of breast feeding within the Unit generally were higher than the national average. The relevance of the RCT for investigating this subject is also discussed with reference to the present data set. Further experimental work to develop these ideas and to identify causal links is required.

Coordination of care in disease management: opportunities and financial issues.

Patients with end-stage renal disease (ESRD) and pre-ESRD require higher utilization of health care resources. Current reimbursement modalities contribute to the fragmentation of care, and inadequate financial information obscures the fiscal impact disease management's coordination of care can have for this population. Ignoring the extreme costs of the first 3 months of hemodialysis underestimates costs by as much as 16%. Potential areas of coordination and the financial benefits are discussed. In each venue of the care settings of a patient with chronic renal failure (CRF) they may receive excellent service. Too often there is not optimal coordination of care between these venues, and in fact the fragmentation of care can cause unnecessary wear and tear on the patient, and increases the overall expense to a health care system. Understanding sources of fragmentation, reimbursement effects, and potential corrections will enhance the patient's voyage through the system. This article provides some examples of the discoordination that presently exists and financial implications especially during the transition onto dialysis. In patients with end-stage renal disease (ESRD), each arena of care has criteria established to quantitate quality. None of the settings, whether it is the dialysis unit, the hospital, the skilled nursing facility, or the physician's office, exists in the absence of regulations. These may be state or federal, National Council on Quality Assurance (NCQA), Health Plan Employer Data and Information Set (HEDIS), water standards, Occupational Safety and Health Administration (OSHA), fire codes, physician peer review, Medicare billing, Health Care Finance Administration (HCFA), the ESRD networks, credentialing, health maintenance organization (HMO) insurance requirements, pharmacy benefits and formularies, safe harbors, "antikickback," or National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) guidelines. For all the providers of care, the other critical component is the ability to have adequate income to stay in business, and make a profit. Each becomes very astute at working within the confines of the regulatory restrictions to provide good care. However, the continuity of care cannot be the overwhelming issue for many of the providers. The only person that is involved in every arena is the patient. The only provider that currently crosses over most arenas is the nephrologist. But the other element that exists in each arena is a payer.

Implementing outcomes management systems in mental health settings.

Outcomes management has received considerable attention in the literature on mental health services delivery. However, relatively little practical information is available on how to implement an outcomes management system in the mental health care setting. The authors review seven key issues that must be addressed in planning such a system: involving senior organizational leaders in ownership of the project, securing the support of clinicians and patients, selecting personnel to operate the system, choosing outcomes assessment instruments, developing data collection procedures, selecting techniques for data management, and using the data to improve outcomes. Ultimately, an outcomes management system is intended to generate data that can be used to stimulate discussion, to guide clinicians in tailoring treatments, and to identify efficient treatment approaches.

Severe preeclampsia with fulminant and extreme elevation of aspartate aminotransferase and lactate dehydrogenase levels: high risk for maternal death.

We report a subgroup of patients with fulminant hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome, manifesting extreme elevation of aspartate aminotransferase (AST; SGOT) and lactate dehydrogenase (LDH) levels and abnormal mental status. These gravidas are at high risk for mortality. Only four patients treated by the authors over a 10-year period have had AST more than 2000 IU/L and LDH more than 3000 IU/L in the HELLP syndrome. This report is based on retrospective chart review. All patients manifested disordered mental status, jaundice, intense hemolysis, and extreme hypertension. One patient had developed multiple organ system failure, was moribund at initial perinatal consultation, and died. The three others were treated with aggressive afterload reduction and plasma infusion or plasmapheresis; two survived. Fulminant HELLP syndrome occurs rarely, but marks a group of patients at high risk for mortality. Optimal therapy is unclear; early intervention, including afterload reduction, volume expansion, and consideration of plasma infusions or plasmapheresis, is recommended.

Isolation and in vitro phosphorylation of sensory transduction components controlling anaerobic induction of light harvesting and reaction center gene expression in Rhodobacter capsulatus.

Anaerobic induction of light harvesting and reaction center gene expression involves two transacting factors termed RegA and RegB. Sequence and mutational analysis has indicated that RegA and RegB constitute cognate components of a prokaryotic sensory transduction cascade with RegB comprising a membrane-spanning sensor kinase and RegA a cytosolic response regulator. In this study we have purified RegA, as well as a truncated portion of RegB (RegB') and undertaken an in vitro analysis of autophosphorylation and phosphotransfer activities. Incubation of RegB' with [gamma-32P]ATP and MgCl2 resulted in phosphorylation of RegB' (RegB' approximately P) over a 20-min incubation period. Incubation of RegB' approximately P with RegA resulted in rapid transfer of the phosphate from RegB' to RegA. In analogy to other characterized prokaryotic sensory transduction components, mutational and chemical stability studies also indicate that RegB' is autophosphorylated at a conserved histidine and that RegA accepts the phosphate from RegB at a conserved aspartate.

Identification and molecular genetic characterization of a sensor kinase responsible for coordinately regulating light harvesting and reaction center gene expression in response to anaerobiosis.

Our laboratory recently demonstrated that anaerobic induction of light harvesting and reaction center structural gene expression involved a trans-acting factor, RegA, which exhibits sequence similarity to the class of prokaryotic sensory transduction proteins known as response regulators (M. W. Sganga and C. E. Bauer, Cell 68:945-954, 1992). In this study, we performed a screen for additional genes involved in inducing anaerobic expression of light harvesting and reaction center structural genes. This search resulted in the isolation of four strains that were shown by complementation and marker rescue analysis to harbor mutations allelic to the originally described regA mutation and one strain with a mutation found to be linked but nonallelic to regA. Sequence analysis indicated that this additional gene, regB, codes for a polypeptide that exhibits sequence similarity to the prokaryotic family of histidine sensor kinases. Analysis of photosynthesis gene expression in regB mutants indicates that the disruption of regB results in a phenotype that is very similar to that described for regA mutants, namely, a failure to trans activate anaerobic expression of the puf, puh, and puc operons. In analogy to other prokaryotic sensory transduction systems, we propose that RegB functions as a membrane-spanning sensor kinase that controls the anaerobic phosphorylation state of RegA, which in turn controls the induction of light harvesting and reaction center structural genes.

Control of photosystem genes in Rhodobacter capsulatus.

Two environmental factors, oxygen and high light intensity, are known to repress synthesis of the Rhodobacter capsulatus photosystem. One level of regulation is the control of light harvesting and reaction centre gene expression at the point of transcription initiation. This has recently been shown to involve transcriptional activators which exhibit sequence similarity to members of the 'two-component' class of prokaryotic regulators. An additional level of regulation involves the formation of 'superoperons' that transcriptionally link pigment biosynthesis operons with operons that code for the light harvesting and reaction centre structural genes. A final level of regulation involves the selective degradation of reaction centre mRNA transcripts which influence the stoichiometric synthesis of the light harvesting and reaction centre complexes.

Bilateral renal artery stenosis: presenting as a case of scleroderma renal crisis.

A patient with long-standing scleroderma who developed malignant hypertension is presented. Renal insufficiency aggravated by the use of angiotensin-converting-enzyme inhibition prompted renal angiography. The latter demonstrated bilateral renal artery stenosis, an uncommon coexistence of two infrequent disorders.

Thrombotic thrombocytopenic purpura in human immunodeficiency (HIV)-seropositive males.

Two male patients with thrombotic thrombocytopenic purpura (TTP) were found to have antibodies to the human immunodeficiency virus (HIV). In one patient, platelet-associated antibody levels were measured serially and were found to be initially elevated, but the levels decreased with initiation of successful therapy. The simultaneous occurrence of these two conditions in two of three patients admitted for TTP within the previous 2 years at this institution suggests an association between the two diseases. The precise nature of this association remains speculative inasmuch as the pathogenesis of TTP remains uncertain.

Association of the level of G gamma chain in the fetal hemoglobin of normal adults with specific haplotypes.

The levels of G gamma chain in the fetal hemoglobin of more than 40 Black and Caucasian females were determined with a sensitive high performance liquid chromatography procedure and were correlated with their haplotypes, defined by the presence or absence of 10 different restriction sites. Blood was collected during the 16th and 31st week of pregnancy because of a slightly elevated level of Hb F which facilitated the isolation of this protein from a relatively small sample. Four distinct G gamma levels were observed, each being associated with a specific haplotype. Homozygosity for sub-haplotype A [- + + - + +] is associated with high G gamma values (60-70%); that for sub-haplotype B [- - - - - +] with low levels (25-30%); and that for sub-haplotype C [+ - - - - -] with very low levels (10-15%) (restriction sites listed are Hinc II at epsilon; Xmn I 5' to G gamma; Hind III at G gamma and A gamma; Hinc II at psi beta and 3' to it). Sub-haplotype D [(14)- + - - +] with a rare polymorphism 5' to epsilon is associated with extremely high G gamma values. Hb F levels were low (less than 2.5%) and were independent of the haplotype. It is speculated that, yet unknown, variations in the DNA of gene activity controlling regions are responsible for the differences in G gamma value.

Enkephalins in pheochromocytoma: studies in a rat model.

Enkephalins, endogenous opioid pentapeptides which are found in high concentration in normal chromaffin tissue, may play a role in blood pressure regulation. We therefore examined the presence and actions of enkephalins in pheochromocytoma in a rat model. Transplantable norepinephrine-rich tumors, which gave rise to significant blood pressure elevations, contained measurable immunoreactive enkephalins as determined by specific radioimmunoassays for leucine-enkephalin and methionine-enkephalin. Enkephalin immunoreactivity paralleled the enkephalin assay standard curves and was not abolished by boiling or by protease inhibitors (EDTA, PMSF). Authenticity of the immunoreactive enkephalins was confirmed by reverse-phase high pressure liquid chromatography. The amount of enkephalin immunoreactivity present initially in these tumors was greatly augmented by the prohormone activators trypsin or trypsin plus carboxypeptidase B, suggesting that most of the immunoreactive enkephalin was present in higher molecular weight precursor form. Enkephalin determinations on human pheochromocytoma and catecholamine measurements in both rat and human pheochromocytoma, demonstrated certain similarities and differences in enkephalin and catecholamine content between rat and human tumors. Total tumor enkephalins correlated (r = 0.91, p less than 0.05) with total tumor catecholamines in rat pheochromocytoma, suggesting co-regulation of synthesis of these 2 chromaffin tissue substances. Physiologic studies, in which intravenous leucine-enkephalin and the opioid antagonist nalaxone were administered to pheochromocytoma-implanted rats and sham-operated controls, failed to uncover an opioid peptide influence upon blood pressure in this animal model of pheochromocytoma.

Contrasting renal haemodynamic responses to the angiotensin converting enzyme inhibitor enalapril and the beta-adrenergic antagonist metoprolol in essential hypertension.

The individual target organ response to blood pressure reduction is an important criterion in the selection of appropriate antihypertensive therapy. We assessed both the renal and the systemic haemodynamic responses to antihypertensive monotherapy (five to seven weeks) with the angiotensin converting enzyme (ACE) inhibitor enalapril (n = 12), in contrast to the cardioselective beta-adrenergic blocker metoprolol (n = 11) in subjects with essential hypertension. Enalapril lowered systolic and diastolic blood pressure, and the fall in blood pressure was mediated haemodynamically by a 34% fall in systemic vascular resistance. In the kidney, glomerular filtration rate, renal plasma flow and renal blood flow were maintained by a 23% fall in renal vascular resistance. The disproportionate fall in systemic resistance versus renal resistance actually reduced the renal fraction of cardiac output. By contrast, metoprolol lowered predominantly diastolic blood pressure, with an associated 25% fall in cardiac output, without significant changes in overall systemic vascular resistance. In the renal circulation, renal perfusion was well maintained by a 20% fall in renal vascular resistance, perhaps at the efferent arteriole, without change in the renal fraction of cardiac output. Neither drug altered weight, plasma volume or total blood volume. Thus, each drug represents effective antihypertensive monotherapy, with a generally favourable, though different, renal haemodynamic profile, characterized by effective autoregulation of renal perfusion even in the face of a fall in perfusion pressure.

Comparative effects of antihypertensive therapy with guanabenz and propranolol on renal vascular resistance and left ventricular mass.

There is increasing interest in initial therapy of hypertension with sympatholytic agents and the influence of antihypertensive therapy on cardiac and renal function. We treated 26 men with essential hypertension with either guanabenz alone (n = 14) or propranolol alone (n = 12) and assessed blood pressure and renal perfusion before and after 5-7 weeks of treatment. Cardiac performance was evaluated for the guanabenz-treated patients. Both drugs substantially reduced blood pressure without weight gain. During guanabenz therapy, glomerular filtration rate and renal blood flow were preserved, with a fall in renal vascular resistance (from 12,100 +/- 1,500 to 9,300 +/- 1,190 dyne X s X cm-5, p less than 0.01). Propranolol decreased glomerular filtration rate (from 95 +/- 11 to 70 +/- 6 ml/min, p less than 0.05) without significant change in renal blood flow or renal vascular resistance. In guanabenz-treated patients, there was a decline in left ventricular mass (from 290 +/- 23 to 257 +/- 14 g, p = 0.067). Thus, both agents are effective initial therapy in hypertension. Guanabenz treatment also was associated with reduced renal vascular resistance and left ventricular mass.