Transvenous Versus Epicardial Pacing in Fontan Patients.

Up to 10% of Fontan patients require pacemakers; an epicardial approach has historically been used. A transvenous approach can be used but carries risk of Fontan obstruction, thromboembolism, and can be technically challenging. The safety and efficacy of these approaches is not well described. The aim of this study was to compare epicardial and transvenous pacemaker outcomes in Fontan patients, specifically, device performance and adverse event rate. A retrospective review was performed on Fontan pacemaker patients followed at a single institution. Thirty-one Fontan pacemaker patients were identified between 1985 and 2017. Twenty-six had an epicardial system, five transvenous, and three converted from epicardial to transvenous. Average atrial lead sensing at placement was 3.23 versus 2.35 mV (p = 0.52) for epicardial and transvenous leads, respectively. Median atrial and ventricular lead longevity was 86.4 versus 98.8 months (p = 0.56) and 73.2 versus 140 months (p = 0.3) with generator longevity of 65.5 versus 73.9 (p = 0.16) months for epicardial versus transvenous systems, respectively. One major complication occurred in a transvenous patient, and two minor complications occurred in epicardial patients. All transvenous patients received warfarin except one, who converted to dabigatran. Epicardial patients received aspirin (n = 20), warfarin (n = 3) or a warfarin/aspirin combination (n = 3). No thromboembolic events occurred. System revision was required in 13 epicardial and 5 transvenous patients. There were two deaths, none related to the pacemaker system. Transvenous pacemakers can be utilized with equal efficacy compared to epicardial pacemakers with trends toward longer lead longevity in transvenous pacemaker systems.

Postmating isolation and genetically variable host use in ecologically divergent host forms of Neochlamisus bebbianae leaf beetles.

Ecological speciation studies have more thoroughly addressed premating than postmating reproductive isolation. This study examines multiple postmating barriers between host forms of Neochlamisus bebbianae leaf beetles that specialize on Acer and Salix trees. We demonstrate cryptic isolation and reduced hybrid fitness via controlled matings of these host forms. These findings reveal host-associated postmating isolation, although a nonecological, 'intrinsic' basis for these patterns cannot be ruled out. Host preference and performance results among cross types further suggest sex-linked maternal effects on these traits, whereas family effects indicate their genetic basis and associated variation. Genes of major effect appear to influence these traits. Together with previous findings of premating isolation and adaptive differentiation in sympatry, our results meet many assumptions of 'speciation with gene flow' models. Here, such gene flow is likely asymmetric, with consequences for the dynamics of future ecological divergence and potential ecological speciation of these host forms.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life.

PURPOSE: This systematic review aimed to assess the literature for prevalence, severity, and impact on quality of life of salivary gland hypofunction and xerostomia induced by cancer therapies. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. Two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results and conclusions for each article. RESULTS: The inclusion criteria were met by 184 articles covering salivary gland hypofunction and xerostomia induced by conventional, 3D conformal radiotherapy or intensity-modulated radiotherapy in head and neck cancer patients, cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment, and immunotherapy. CONCLUSIONS: Salivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact.

PURPOSE: This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. RESULTS: Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. CONCLUSIONS: There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.

A compact filtered x-ray diode array spectrometer for the National Ignition Facility: SENTINEL.

Sentinel is a 16-channel, filtered x-ray diode array spectrometer that has been developed to measure ∼1 keV-20 keV x-ray emission generated by the National Ignition Facility (NIF) laser. Unlike the large, fixed-port versions of this diagnostic that currently exist on the NIF (known as Dante), Sentinel is a Diagnostic Instrument Manipulator compatible such that it can be fielded along the polar or equatorial lines-of-sight-an essential new capability for characterizing the often anisotropic x-ray emission from laser-driven sources. We present the diagnostic design along with preliminary diode calibrations and performance results. The novel, small-form-factor x-ray diode design allows for ≳5×-25× increased channel areal density over that of Dante, simultaneously enabling improved diagnostic robustness and fidelity of spectral reconstructions. While the Sentinel diagnostic is anticipated to improve line-of-sight spectral characterization of x-ray sources for a wide variety of programs on the NIF, the compact and portable design is also attractive to small- and mid-scale facilities with limited diagnostic real estate.

Advances in x-ray framing cameras at the National Ignition Facility to improve quantitative precision in x-ray imaging.

We describe an experimental method to measure the gate profile of an x-ray framing camera and to determine several important functional parameters: relative gain (between strips), relative gain droop (within each strip), gate propagation velocity, gate width, and actual inter-strip timing. Several of these parameters cannot be measured accurately by any other technique. This method is then used to document cross talk-induced gain variations and artifacts created by radiation that arrives before the framing camera is actively amplifying x-rays. Electromagnetic cross talk can cause relative gains to vary significantly as inter-strip timing is varied. This imposes a stringent requirement for gain calibration. If radiation arrives before a framing camera is triggered, it can cause an artifact that manifests as a high-intensity, spatially varying background signal. We have developed a device that can be added to the framing camera head to prevent these artifacts.

X-ray transport and radiation response assessment (XTRRA) experiments at the National Ignition Facility.

Our team has developed an experimental platform to evaluate the x-ray-generated stress and impulse in materials. Experimental activities include x-ray source development, design of the sample mounting hardware and sensors interfaced to the National Ignition Facility's diagnostics insertion system, and system integration into the facility. This paper focuses on the X-ray Transport and Radiation Response Assessment (XTRRA) test cassettes built for these experiments. The test cassette is designed to position six samples at three predetermined distances from the source, each known to within ±1% accuracy. Built-in calorimeters give in situ measurements of the x-ray environment along the sample lines of sight. The measured accuracy of sample responses as well as planned modifications to the XTRRA cassette is discussed.

Bos taurus and Bos indicus (Sahiwal) calves respond differently to infection with Theileria annulata and produce markedly different levels of acute phase proteins.

Disease-resistant livestock could provide a potentially sustainable and environmentally sound method of controlling tick and tick-borne diseases of livestock in the developing world. Advances in the knowledge and science of genomics open up opportunities to identify selectable genes controlling disease resistance but first, breeds and individuals with distinguishable phenotypes need to be identified. The Bos indicus breed, Sahiwal, has been exploited in dairy breeding programmes, because it is resistant to ticks and has relatively good performance characteristics compared to other indigenous cattle breeds of tropical regions. The analyses reported here show that Sahiwal calves were also more resistant than European Bos taurus (Holstein) dairy breed calves to tick-borne tropical theileriosis (Theileria annulata infection). Following experimental infection with T. annulata sporozoites, a group of Sahiwal calves all survived without treatment, with significantly lower maximum temperatures (P<0.01) and lower rates of parasite multiplication (P<0.05) than a group of Holstein calves, which all had severe responses. Although the Sahiwals became as anaemic as the Holsteins, other measures of pathology, including enlargement of the draining lymph node and the acute phase proteins, alpha1 acid glycoprotein and haptoglobin, were significantly less in the Sahiwals than in the Holsteins (P<0.05). Additionally, the Sahiwals had significantly lower resting levels of alpha1 acid glycoprotein than the Holsteins (P<0.05). Production of a third acute phase proteins, serum amyloid A, had very similar kinetics in both breeds. Acute phase proteins are produced in response to systemic release of the kinds of pro-inflammatory cytokines that are thought to be responsible for the pyrexic, cachectic and anorexic responses characteristic of tropical theileriosis. The prolonged production of alpha1 acid glycoprotein in the Holsteins is indicative of chronic production of circulating pro-inflammatory cytokines. In contrast, Sahiwals appear able to overcome infection with T. annulata as well as limit pathology by preventing the over-stimulation of pathways involving these cytokines.

In vivo comparison of susceptibility between Bos indicus and Bos taurus cattle types to Theileria parva infection.

The objective of this study was to determine whether Bos taurus cattle differ form Bos indicus in their susceptibility to infection with the Muguga stabilate of Theileria parva and in their resistance to the resultant disease. Ten Friesians (B. taurus), ten improved Borans (B. indicus), ten unimproved Borans (B. indicus) and ten Zebus (B. indicus) born to dams from an East Coast fever (ECF) endemic area were inoculated with an infective dose50 dilution of T. parva Muguga stabilate 147. All the animals except one Friesian and one Zebu developed schizont parasitosis. All the improved Borans, nine of the Friesians, eight of the unimproved Borans and six of the Zebus developed a febrile response. Four of the improved Borans, four of the Friesians and three of the unimproved Borans died of theileriosis. No significant difference (P > 0.05) in the prepatent period occurred between the groups, but the Zebus had a significantly shorter duration of schizont parasitosis (P > 0.05) and took a significantly shorter time to recover (P > 0.05) than the other three groups. There was no significant difference in the two parameters between the other three groups. The study showed that three B. indicus breds and a B. taurus breed are equally susceptible to T. parva infection. However, Zebus born to dams from an ECF endemic area showed a better ability to control the course of disease than cattle from ECF free areas.

Studies on the control of prostaglandin production by the hypothalamus in relation to LH release in the rat.

Prostaglandin (PG) and thromboxane (TX) synthesis by homogenates of the hypothalamus of rats has been measured in relation to the preovulatory surge of LH. Prostaglandin and TX production by the median eminence (ME) was five to ten times higher than that by the anterior hypothalamus/preoptic area (AH-POA). Prostaglandin E2 and PGF2 alpha were the major prostaglandins synthesized by the ME and AH-POA respectively. During the 4-day oestrous cycle, the PG- and TX-synthesizing capacity of the ME showed daily changes, being high at 06.00 and 22.00 h and, with the exception of pro-oestrus, low at 18.00 h. There was an additional peak of PGE2 production by the ME at 18.00 h on pro-oestrus coincident with the preovulatory LH surge. Progesterone treatment stimulated PGE2 synthesis by the ME of long-term ovariectomized, oestradiol-primed rats but not by the ME of acutely ovariectomized, oestradiol-primed rats. 2-Hydroxyoestradiol had no effect on PG and TX production by the ME at 18.00 h on dioestrus or 18.00 h on pro-oestrus. Noradrenaline stimulated PG and TX synthesis by the ME at the former time but not at the latter time. Prostaglandin F2 alpha-synthesizing capacity of the AH-POA peaked at 22.00 h on each day of the 4-day cycle. There was also an additional peak at 14.00 h on each day except dioestrus. Similar peaks occurred in the production of PGE2 and TXB2, except on pro-oestrus when the production of each compound remained low. There was no association between increased PGE2 production by the AH-POA and the preovulatory surge of LH. Noradrenaline, but not 2-hydroxyoestradiol, stimulated PG and TX production by the AH-POA at 18.00 h on both dioestrus and pro-oestrus. Progesterone stimulated PGE2, PGF2 alpha and 6-oxo-PGF1 alpha production by the AH-POA of acute, ovariectomized, oestradiol-primed rats but not of long-term ovariectomized, oestradiol-primed rats. Flurbiprofen, a cyclo-oxygenase inhibitor, prevented the preovulatory LH surge in two rats and delayed the LH surge by 2 h in four rats. It also reduced PG and TX production by the ME and AH-POA. Overall, the present studies show that there is an increase in PGE2-synthesizing capacity of the ME at the time of the preovulatory LH surge in the rat, and that the administration of an inhibitor of prostaglandin synthesis interferes with the timing of the LH surge.

Oestrogen-2/4-hydroxylase activity in the rat brain during lactation and throughout the oestrous cycle.

Oestrogen-2/4-hydroxylase activity was measured in whole brain, thalamus, amygdala, hypothalamus and pituitary gland of lactating rats and in whole brain of rats on different days of the oestrous cycle. Enzyme activity was increased in whole brain and in each of the brain regions examined (with the exception of the amygdala) in lactating rats. This increase in enzyme activity was associated with an increase in serum prolactin levels. During the oestrous cycle, enzyme activity in whole brain was higher on metoestrus and dioestrus than on pro-oestrus and oestrus. The decrease in enzyme on pro-oestrus was associated with an increase in both serum oestradiol and prolactin levels. These results are consistent with the hypothesis that changes in oestrogen-2/4-hydroxylase activity are associated with changes in prolactin and oestradiol secretion and may play a regulatory role in reproduction.

The protozoan parasite, Theileria annulata, induces a distinct acute phase protein response in cattle that is associated with pathology.

Acute phase proteins (APP) are synthesised in the liver in response to the systemic presence of high levels of pro-inflammatory cytokines. Bacteria are considered to be strong inducers of APP whereas viruses are weak or non-inducers of APP. Very few reports have been published on APP induction by parasites. Here, we report that the tick-borne protozoan parasite of cattle, Theileria annulata, induced an atypical acute phase response in cattle. Following experimental infection, serum amyloid A (SAA) appeared first, followed by a rise in alpha(1) acid glycoprotein (alpha(1)AGP) in all animals, whereas haptoglobin, which is a major APP in cattle, only appeared in some of the animals, and generally at a low level. All three APP only became elevated around or after the appearance of schizonts in draining lymph nodes and after the first observed temperature rise. Increased alpha(1)AGP levels coincided with the appearance of piroplasms. The production of SAA and alpha(1)AGP correlated strongly with each other, and also with some clinical measures of disease severity including the time to fever, development of leucopaenia, parasitaemia and mortality. These results are consistent with the hypothesis that T. annulata causes severe pathology in susceptible cattle by inducing high levels of pro-inflammatory cytokines.

Analysis of the ventricular fibrillation ECG signal amplitude and frequency parameters as predictors of countershock success in humans.

OBJECTIVE: The purpose of this study was to assess from the ventricular fibrillation ECG signal whether certain amplitude parameters, or frequency parameters derived using fast Fourier transform analysis, are predictive of countershock success (defined as a stable supraventricular rhythm following countershock). DESIGN: Retrospective, descriptive study. SETTING: Emergency medical service at a university hospital. PATIENTS: Twenty-six patients with out-of-hospital cardiac arrest, whose initial ECG rhythm was identified as ventricular fibrillation. METHODS AND RESULTS: In all patients, advanced cardiac life support was performed in the out-of-hospital setting and a semiautomatic defibrillator was used for countershock therapy and simultaneous on-line ECG recording. For each patient, ECG data were stored in modules in digitized form over a period of 20 min and analyzed retrospectively. Using fast Fourier transform analysis of the ventricular fibrillation ECG signal in the frequency range of 0.3 to 30 Hz (mean +/- SD), median frequency, dominant frequency, edge frequency, and amplitude were as follows: 5.17 +/- 1.05 Hz, 4.56 +/- 0.99 Hz, 10.74 +/- 3.46 Hz, and 1.33 +/- 0.44 mV before successful countershock (n = 20); and 4.21 +/- 1.17 Hz (p = 0.0034), 3.31 +/- 1.57 Hz (p = 0.0004), 9.46 +/- 2.93 Hz (p = 0.5390), and 1.15 +/- 0.69 mV (p = 0.0134) before unsuccessful countershock (n = 134). Using software filters to completely eliminate interference due to manual cardiopulmonary resuscitation from the ventricular fibrillation power spectrum, only amplitude remained statistically different (p < or = 0.03) in predicting countershock success. CONCLUSIONS: We conclude that in patients, median frequency, dominant frequency, and amplitude are predictive of countershock success in humans.

Median fibrillation frequency in cardiac surgery: influence of temperature and guide to countershock therapy.

OBJECTIVE: This study was designed (1) to investigate the effects of normothermic and hypothermic perfusion on the median frequency of the fibrillating myocardium, and (2) to elucidate whether frequency-guided countershock therapy improves countershock success during the reperfusion phase of cardiac surgery. DESIGN: Prospective, randomized study. SETTING: University hospital cardiac surgery room. PATIENTS: Thirty patients (first part of the study) and 38 patients (second part of the study) scheduled for elective coronary artery bypass surgery. METHODS AND RESULTS: During cardiopulmonary bypass, ventricular fibrillation (VF) was induced at a core body temperature of 34.1+/-0.2 degrees C (normothermia) (n=15) or at a core body temperature of 29.8+/-0.2 degrees C (hypothermia) (n=15). Using fast Fourier transformation of the ECG signal, median fibrillation frequency was recorded continuously for a period of 120 s. At the end of surgery, countershock was performed as soon as VF was recognized on the ECG monitor (X Hz group; n=19) or countershock was not performed until median fibrillation frequency had increased to the threshold of at least 5 Hz (5 Hz group; n=19). Median fibrillation frequency in the normothermic fibrillation group was statistically higher than in the hypothermic group. In the X Hz and 5 Hz countershock group, median fibrillation frequency before the first countershock attempt was 3.6+/-0.2 Hz and 5.4+/-0.1 Hz (p<0.0001), respectively. In the X Hz group, six countershocks resulted in supraventricular rhythm, 10 in VF, two in electromechanical dissociation, and one in asystole. In the 5 Hz group, 16 countershocks resulted in supraventricular rhythm, two in VF, and one in asystole (p=0.008). CONCLUSIONS: During normothermia, median fibrillation frequency is significantly higher than during hypothermic perfusion conditions. During the reperfusion phase of cardiac surgery, countershock success rate is significantly higher when a threshold of at least 5 Hz had been reached before the first countershock attempt.

Theileria annulata: carrier state and immunity.

Recovery from primary infection of Theileria annulata results in the development of a persistent carrier state in the vertebrate host. The carrier state is of great importance in the maintenance of the life cycle by alternate tick/cattle challenge and both contributes to and may be necessary for maintenance of immunity. Therefore, an accurate determination of carrier animals could be useful in determining immune status and may allow the necessary control measures to be implemented. Detailed information on the carrier state of animals following immunization with attenuated cell lines is lacking. In this study, relationship between immune response, persistence of the parasite, and the antibody response has been investigated. Calves were infected with T. annulata sporozoites, low passage (non-attenuated) or high passage (attenuated, vaccine) cell lines and later challenged with a lethal dose of heterologous sporozoites. The presence and persistence of the parasite were monitored by PCR using primers derived from genes coding for ssrRNA and a 30 kDa major merozoite surface protein, by Giemsa stained blood smears to detect the presence of piroplasms and also by attempting to establish infected mononuclear cell cultures from venous blood. Antibody responses were measured by indirect ELISA using a merozoite recombinant antigen and IFAT using piroplasm and macroschizont antigens. Results showed that there was an evident relationship between the persistence of carrier status, antibody response in ELISA and immune response to challenge.

Theileria lestoquardi and T. annulata in cattle, sheep, and goats. In vitro and in vivo studies.

Theileria annulata, causing bovine tropical theileriosis, and T. lestoquardi (syn T. hirci), the agent of malignant ovine theileriosis, are both transmitted by ticks of the genus Hyalomma. Their distribution is thus very similar and, should these parasites infect more than one ruminant species, the difficulty in interpreting epidemiological studies is magnified considerably. A pilot series of experiments was thus conducted in which cattle, sheep and goats were infected with sporozoites of a single stock of each of T. annulata and T. lestoquardi from a laboratory colony of H.a.anatolicum. Reciprocal cross-immunity and serological studies and in vitro culture isolations in mononuclear cells of each ruminant species illustrated both the similarity of these organisms and their differences. The importance of these findings in discriminating parasites in epidemiological studies and the control of these diseases with cell culture vaccines is emphasized.

Different vaccine strategies used to protect against Theileria annulata.

SPAG-1, a sporozoite surface antigen of T. annulata, has previously been shown to elicit partial protection when used, as an hepatitis B core antigen fusion, to immunize cattle. The objective of this study was to try and improve the protective capacity of this antigen by enlisting different vaccine strategies. Cattle were immunized with SPAG-1, as a fusion protein with a His6 tag, either incorporated into ISCOMs, with or without the merozoite antigens TAMS 1-1 and 1-2, or with RWL as adjuvant three times at monthly intervals. Another group of cattle were immunized with p67, the T. parva sporozoite antigen, in RWL to assess whether any cross-protection could be induced. The animals were then challenged with an estimated LD50 of T. annulata sporozoites, and their ability to resist the infection was investigated. Serum responses and T-cell proliferative responses were analyzed throughout the trial. Post-challenge analyses included lymph node biopsies and blood smears to check for the presence of parasites, routine hematological parameters, and observation for clinical manifestations of the disease. The results of this trial will be discussed.

Studies on the effect of chronic L-triiodothyronine (T3) treatment on brain Na+,K+-ATPase activity in the mature rat.

Mature rats were dosed with T3 by different routes and dose-levels at either 0.1 mg/kg for 14 days s.c. (Group A), 1 mg/kg for 3 alternative days i.p. (Group B), 5 mg/kg for 14 days p.o. (Group C), or with propylthiouracil (PTU 50 mg/day for 14 days p.o.-Group D). Measurement of cerebellar and striatal NA+,K+-ATPase activities showed that whereas Groups A, B and D were unaffected when compared with controls, there were 35-70% increases respectively in the activities of both molecular forms of the enzyme, alpha(+), high ouabain affinity, and alpha, low ouabain affinity, in Group C rat brains at the highest dose of T3 tested. Kidney Na+,K+-ATPase activity was also elevated (67% increase) in this group of animals showing significant changes in renal medullary tissue only. Acute elevation of brain dopamine levels by administration of an MAOI plus L-DOPA (50 mg/kg, 60 min) significantly elevated (20% increase) the activities of both molecular forms of Na+,K+-ATPase in corpus striatum. Treatment with L-tryptophan (50 mg/kg, 60 min) failed to produce any changes in the striatal activities. The possible relationship of increases in enzyme activities with T3 and increased brain monoamine function is discussed. Both plasma free T4(FT4) and total T4(TT4) were markedly depressed in all T3-treated rats. Although hypothalamic thyrotropin releasing hormone (TRH) concentrations were unaltered by any of the T3 treatments, pituitary thyroid stimulating hormone (TSH) concentrations were greatly diminished and it is thought that this may reflect a direct effect of T3 on TSH synthesis.

Differential effects of D- and L-isomers of triiodothyronine on pituitary TSH secretion and peripheral deiodinase activity in the rat.

The effects of D- and L-T3 were compared in male SK & F Wistar rats to define overall effects on the 'pituitary-thyroid-liver axis' at high doses. After in vivo administration of L-T3 (up to 1 mg/kg orally, or up to 0.1 mg/kg subcutaneously) serum TSH and T4 were decreased in a dose-related manner. Similarly, following in vivo exposure to L-T3, both basal and TRH-stimulated TSH output from isolated superfused pituitary glands was decreased, but only the latter was affected by direct in vitro exposure to L-T3.D-T3 had between 1% and 10% the activity of L-T3 in decreasing these parameters both in vivo and in vitro. In contrast, both enantiomers increased liver and kidney deiodinase activity to approximately the same extent, presumably as a compensatory response to clear hormone from the body. These observations indicate that, following treatment with L- or D-T3 by oral gavage for 14 days, the 'no effect' dose (i.e. the dose which did not significantly decrease serum TSH concentrations as compared with controls) for L-T3 was below 0.01 mg/kg whereas that for D-T3 was 0.1 mg/kg.

Adrenergic agonists during cardiopulmonary resuscitation.

A number of studies have suggested that following a prolonged cardiopulmonary arrest, large doses of alpha-adrenergic agonists that possess post-synaptic alpha-2 agonist properties, i.e. epinephrine and norepinephrine, may be required to enhance myocardial and cerebral hemodynamics. While initial human studies using large doses of epinephrine have shown improved hemodynamics over standard therapy, hospital discharge rates and neurological outcome have been discouraging. This probably reflects the fact that the administration of epinephrine was employed late in the resuscitation effort. Future studies using larger doses of epinephrine as the initial pharmacologic intervention during cardiopulmonary resuscitation (CPR) will help to determine whether there is any therapeutic benefit. In addition, a number of questions still remain unanswered in delineating the specific alpha and beta adrenergic agonist components which will maximally enhance hemodynamics and resuscitation rates during CPR. This will help determine whether norepinephrine or a yet unsynthesized adrenergic agonist may be more beneficial for use during cardiac arrest.