bluuebunny/crossref_metadata_2025 huggingface dataset:
The JAK2V617F Mutation in Polycythemia Vera and Other Myeloproliferative Disorders: One Mutation for Three Diseases?
Authors: James Chloé
Published: December 2008

The discovery of the JAK2V617F mutation has made the diagnosis of polycythemia vera (PV) much easier, but the pathogenesis of PV is still incompletely understood. In particular, it is not yet elucidated how a single mutation can be found in multiple myeloproliferative disorders (MPD) and myelodysplastic syndromes with ring sideroblasts and whether the sole JAK2V617F is sufficient to induce a MPD in humans. Several hypotheses are under investigation such as differences in the targeted hematopoietic stem cells (HSC), host modifier polymorphisms, intensity of JAK2V617F signaling, presence of other somatic mutations, or the presence of a pre-JAK2 event that may vary according to the MPD phenotype. Multiple studies have provided some evidence for and against each hypothesis, but it now seems possible to reconcile these hypotheses into a model that will need to be tested using newly developed tools. Recent investigations have also led to new treatment modalities that could benefit patients with PV.
Paroxysmal Nocturnal Hemoglobinuria: An Historical Overview
Authors: Parker Charles J.
Published: December 2008

The clinical hallmark of paroxysmal nocturnal hemoglobinuria (PNH) is episodic hemoglobinuria, and it was this feature that captured the attention of European physicians in the latter half of the 19th century, resulting in careful observational studies that established PNH as an entity distinct from paroxysmal cold hemoglobinuria and march hemoglobinuria. Curiosity about the etiology of the nocturnal aspects of the hemoglobinuria led the German physician Paul Strübing to develop the prescient hypothesis that the erythrocytes of PNH are abnormally sensitive to hemolysis when the plasma is acidified during sleep because of accumulation of carbon dioxide and lactic acid as a result of slowing of the circulation. Investigation of the intricate pathophysiology that underlies the abnormal sensitivity of PNH erythrocytes to hemolysis in acidified serum produced a number of remarkable scientific achievements that involved discovery of the alternative pathway of complement, identification of the membrane proteins that regulate complement, discovery of a novel mechanism for attachment of proteins to the cell surface, and identification of the genetic basis of the disease. These discoveries were made steadily over a period of more than 100 years, and each generation of physicians and scientists made important contributions to the field. The mysteries of PNH have been solved in a particularly satisfying way because the precision and orderliness of the solutions made clearly understandable what had seemed at the times prior to resolution to be problems of nearly insurmountable complexity. The history of PNH is an inspirational reminder of the elegant complexity of nature, the rewards of curiosity and the power and beauty of science.
Hallux valgus and hallux rigidus: a comparison of impact on health‐related quality of life in patients presenting to foot surgeons in Australia
Authors: Gilheany Mark F , Landorf Karl B , Robinson Priscilla
Published: December 2008

Background

Hallux valgus and hallux rigidus are common foot conditions that lead to a deterioration in health status. Patients with significant pain or deformity from these conditions frequently resort to surgery. In this project, the foot health status of patients with hallux valgus and hallux rigidus presenting to foot surgeons in Australia was compared.

Methods

Foot health status was measured in 120 participants using the Foot Health Status Questionnaire (FHSQ), a validated 0 – 100 point health status instrument. All participants had presented for surgical advice regarding hallux valgus/rigidus. The mean age of participants was 48.0 years (SD ± 14.3, range 19 – 79).

Results

In the sample, 68% of participants were diagnosed with hallux valgus and 32% with hallux rigidus. Participants with hallux rigidus had greater levels of pain and functional limitation compared with hallux valgus. The mean difference for pain was 13.8 points (95% CI 4.6 to 22.9) and the mean difference for function was 15.0 points (95% CI 5.3 to 24.7). Both conditions result in similarly negative levels of impact on shoe fit and overall foot health.

Conclusion

This study found measurable differences in foot health status between hallux valgus and hallux rigidus in participants presenting for surgical consultation. While both appear to have a negative impact on health status, hallux rigidus has a more significant impact.
The Costs of Remoteness: Evidence from German Division and Reunification
Authors: Redding Stephen J , Sturm Daniel M
Published: December 2008

This paper exploits the division of Germany after the Second World War and the reunification of East and West Germany in 1990 as a natural experiment to provide evidence for the importance of market access for economic development. In line with a standard new economic geography model, we find that, following division, cities in West Germany close to the East-West German border experienced a substantial decline in population growth relative to other West German cities. We show that the model can account for the quantitative magnitude of our findings and provide additional evidence against alternative possible explanations. (JEL F15, N94, R12, R23)
Zombie Lending and Depressed Restructuring in Japan
Authors: Caballero Ricardo J , Hoshi Takeo , Kashyap Anil K
Published: December 2008

Large Japanese banks often engaged in sham loan restructurings that kept credit flowing to otherwise insolvent borrowers (which we call zombies). We examine the implications of suppressing the normal competitive process whereby the zombies would shed workers and lose market share. The congestion created by the zombies reduces the profits for healthy firms, which discourages their entry and investment. We confirm that zombie-dominated industries exhibit more depressed job creation and destruction, and lower productivity. We present firm-level regressions showing that the increase in zombies depressed the investment and employment growth of non-zombies and widened the productivity gap between zombies and non-zombies. (JEL G21, G32, L25)
Pricing-to-Market, Trade Costs, and International Relative Prices
Authors: Atkeson Andrew , Burstein Ariel
Published: December 2008

International relative prices across industrialized countries show large and systematic deviations from relative purchasing power parity. We embed a model of imperfect competition and variable markups in a quantitative model of international trade. We find that when our model is parameterized to match salient features of the data on international trade and market structure in the United States, it can reproduce deviations from relative purchasing power parity similar to those observed in the data because firms choose to price-to-market. We then examine how pricing-to-market depends on the presence of international trade costs and various features of market structure. (JEL F12, F14, F31)
The Effect of Credit Constraints on the College Drop-Out Decision: A Direct Approach Using a New Panel Study
Authors: Stinebrickner Ralph , Stinebrickner Todd
Published: December 2008

A serious difficulty in determining the importance of credit constraints in education arises because standard data sources do not provide a direct way of identifying which students are credit constrained. This paper differentiates itself from previous work by taking a direct approach, made possible by unique longitudinal data from the Berea Panel Study. The results from our study of Berea College students suggest that, while credit constraints likely play an important role in the drop-out decisions of some students, the large majority of attrition of students from low-income families should be primarily attributed to reasons other than credit constraints. (JEL I21, I22)
How Do Budget Deficits and Economic Growth Affect Reelection Prospects? Evidence from a Large Panel of Countries
Authors: Brender Adi , Drazen Allan
Published: December 2008

We test whether good economic conditions and expansionary fiscal policy help incumbents get reelected in a large panel of democracies. We find no evidence that deficits help reelection in any group of countries independent of income level, level of democracy, or government or electoral system. In developed countries and old democracies, deficits in election years or over the term of office reduce reelection probabilities. Higher growth rates over the term raise reelection probabilities only in developing countries and new democracies. Low inflation is rewarded by voters only in developed countries. These effects are both statistically significant and quite substantial quantitatively. (JEL D72, E62, H62, O47)
The Impact of Nearly Universal Insurance Coverage on Health Care Utilization: Evidence from Medicare
Authors: Card David , Dobkin Carlos , Maestas Nicole
Published: December 2008

The onset of Medicare eligibility at age 65 leads to sharp changes in the health insurance coverage of the US population. These changes lead to increases in the use of medical services, with a pattern of gains across socioeconomic groups that varies by type of service. While routine doctor visits increase more for groups that previously lacked insurance, hospital admissions for relatively expensive procedures like bypass surgery and joint replacement increase more for previously insured groups that are more likely to have supplementary coverage after 65, reflecting the relative generosity of their combined insurance package under Medicare. (JEL I11, I18)
Can Hepatitis B Mothers Account for the Number of Missing Women? Evidence from Three Million Newborns in Taiwan
Authors: Lin Ming-Jen , Luoh Ming-Ching
Published: December 2008

The “missing women” phenomenon in many Asian countries has previously been regarded as the result of son preference. However, some studies have argued half of the missing women can be explained by infection with Hepatitis B virus (HBV). We demonstrate that the probability of having a male birth is only slightly higher for HBV mothers than for mothers without HBV. The sex ratio at birth rises for the higher birth order and that in families where the first two children are female. Our findings suggest that HBV status has little impact on the missing women phenomenon. (JEL I12, J16)
COUP-TFII Is Preferentially Expressed in the Caudal Ganglionic Eminence and Is Involved in the Caudal Migratory Stream
Authors: Kanatani Shigeaki , Yozu Masato , Tabata Hidenori , Nakajima Kazunori
Published: December 2008

While the cortical interneurons derived from the medial ganglionic eminence (MGE) migrate rather diffusely into the cortex, interneurons that migrate out from the caudal ganglionic eminence (CGE) mainly move caudally into the caudal cerebral cortex and the hippocampus in the form of the caudal migratory stream (CMS) (Yozu et al., 2005). Although transplantation experiments at embryonic day 13.5 had revealed that the migrating cells in these two populations are already intrinsically different in regard to their ability to respond to the CGE environment (Yozu et al., 2005), it is not known how the CGE cells are specified and how their migratory behavior is determined.

In this study we showed that, although CGE and lateral ganglionic eminence (LGE) express almost the same marker molecules, LGE cells do not migrate caudally when transplanted into the CGE, suggesting that LGE cells are intrinsically different from CGE cells. We therefore compared the transcriptomes of the CGE, MGE, and LGE, and the results showed thatCOUP-TFIIwas expressed preferentially in the CGE as well as in the migrating interneurons in the CMS. Transplantation experiments revealed that COUP-TFII is sufficient to change the direction of MGE cell migration to caudal when transplanted into the CGE environment, and knockdown ofCOUP-TFIIinhibited the caudal migration of the CGE cells. These results suggest that COUP-TFII is both required and sufficient for the CGE-cell-specific migratory behavior in the caudal direction. Thus, a locally expressed transcription factor determines the migratory direction of the cortical interneurons in a region-specific manner.
RIM1α and RIM1β Are Synthesized from Distinct Promoters of theRIM1Gene to Mediate Differential But Overlapping Synaptic Functions
Authors: Kaeser Pascal S. , Kwon Hyung-Bae , Chiu Chiayu Q. , Deng Lunbin , Castillo Pablo E. , Südhof Thomas C.
Published: December 2008

At a synapse, presynaptic terminals form a specialized area of the plasma membrane called the active zone that mediates neurotransmitter release. RIM1α is a multidomain protein that constitutes a central component of the active zone by binding to other active zone proteins such as Munc13 s, α-liprins, and ELKS, and to synaptic vesicle proteins such as Rab3 and synaptotagmin-1. In mice, knockout of RIM1α significantly impairs synaptic vesicle priming and presynaptic long-term plasticity, but is not lethal. We now find that the RIM1 gene encodes a second, previously unknown RIM1 isoform called RIM1β that is upregulated in RIM1α knock-out mice. RIM1β is identical to RIM1α except for the N terminus where RIM1β lacks the N-terminal Rab3-binding sequence of RIM1α. Using newly generated knock-out mice lacking both RIM1α and RIM1β, we demonstrate that different from the deletion of only RIM1α, deletion of both RIM1α and RIM1β severely impairs mouse survival. Electrophysiological analyses show that the RIM1αβ deletion abolishes long-term presynaptic plasticity, as does RIM1α deletion alone. In contrast, the impairment in synaptic strength and short-term synaptic plasticity that is caused by the RIM1α deletion is aggravated by the deletion of both RIM1α and RIM1β. Thus, our data indicate that theRIM1gene encodes two different isoforms that perform overlapping but distinct functions in neurotransmitter release.
Enhanced Sensitivity of Striatal Neurons to Axonal Transport Defects Induced by Mutant Huntingtin
Authors: Her Lu-Shiun , Goldstein Lawrence S. B.
Published: December 2008

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease linked to a polyQ (polyglutamine) expansion in the huntingtin protein. Although general brain atrophy is found in HD patients, the striatum is the most severely affected region. Loss or mutant forms of huntingtin were reported to disrupt fast axonal transport inDrosophila, squid, and mice. However, previous work did not resolve whether mutant huntingtin affects global axonal transport or only a subset of cargoes, nor did it resolve whether striatal neurons are preferentially sensitive to huntingtin-mediated defects. We used amyloid precursor protein (APP)–yellow fluorescent protein and brain-derived neurotrophic factor (BDNF)–mCherry fusion proteins as markers for fast axonal transport when huntingtin is altered. We found that movement of APP and BDNF is impaired in striatal and hippocampal, but not cortical, neurons from presymptomatic homozygous mutant mice carrying 150Q huntingtin knock-in mutations. In addition, loss of huntingtin disrupts APP axonal transport, whereas overexpression of wild-type, but not mutant, huntingtin enhances APP transport in all three types of neurons tested. These data suggest that a loss of wild-type huntingtin function in fast axonal transport plays important roles in the development of cell-type-specific defects in HD.
The Sensory Insular Cortex Mediates the Stress-Buffering Effects of Safety Signals But Not Behavioral Control
Authors: Christianson John P. , Benison Alexander M. , Jennings Joshua , Sandsmark Emilee K. , Amat Jose , Kaufman Richard D. , Baratta Michael V. , Paul Evan D. , Campeau Serge , Watkins Linda R. , Barth Daniel S. , Maier Steven F.
Published: December 2008

Safety signals are learned cues that predict stress-free periods whereas behavioral control is the ability to modify a stressor by behavioral actions. Both serve to attenuate the effects of stressors such as uncontrollable shocks. Internal and external cues produced by a controlling behavior are followed by a stressor-free interval, and so it is possible that safety learning is fundamental to the effect of control. If this is the case then behavioral control and safety should recruit the same neural machinery. Interestingly, safety signals that prevented a behavioral outcome of stressor exposure that is also blocked by control (reduced social exploration) failed to inhibit activity in the dorsal raphé nucleus or use the ventromedial prefrontal cortex, the mechanisms by which behavioral control operates. However, bilateral lesions to a region of posterior insular cortex, termed the “sensory insula,” prevented the effect of safety but not of behavioral control, providing a double-dissociation. These results indicate that stressor-modulators can recruit distinct neural circuitry and imply a critical role of the sensory insula in safety learning.
The Neural Basis for Combinatorial Coding in a Cortical Population Response
Authors: Osborne Leslie C. , Palmer Stephanie E. , Lisberger Stephen G. , Bialek William
Published: December 2008

We have used a combination of theory and experiment to assess how information is represented in a realistic cortical population response, examining how motion direction and timing is encoded in groups of neurons in cortical area MT. Combining data from several single-unit experiments, we constructed model population responses in small time windows and represented the response in each window as a binary vector of 1s or 0s signifying spikes or no spikes from each cell. We found that patterns of spikes and silence across a population of nominally redundant neurons can carry up to twice as much information about visual motion than does population spike count, even when the neurons respond independently to their sensory inputs. This extra information arises by virtue of the broad diversity of firing rate dynamics found in even very similarly tuned groups of MT neurons. Additionally, specific patterns of spiking and silence can carry more information than the sum of their parts (synergy), opening up the possibility for combinatorial coding in cortex. These results also held for populations in which we imposed levels of nonindependence (correlation) comparable to those found in cortical recordings. Our findings suggest that combinatorial codes are advantageous for representing stimulus information on short time scales, even when neurons have no complicated, stimulus-dependent correlation structure.
SynGAP Regulates Steady-State and Activity-Dependent Phosphorylation of Cofilin
Authors: Carlisle Holly J. , Manzerra Pasquale , Marcora Edoardo , Kennedy Mary B.
Published: December 2008

SynGAP, a prominent Ras/Rap GTPase-activating protein in the postsynaptic density, regulates the timing of spine formation and trafficking of glutamate receptors in cultured neurons. However, the molecular mechanisms by which it does this are unknown. Here, we show that synGAP is a key regulator of spine morphology in adult mice. Heterozygous deletion ofsynGAPwas sufficient to cause an excess of mushroom spines in adult brains, indicating that synGAP is involved in steady-state regulation of actin in mature spines. Both Ras- and Rac-GTP levels were elevated in forebrains from adultsynGAP+/−mice. Rac is a well known regulator of actin polymerization and spine morphology. The steady-state level of phosphorylation of cofilin was also elevated insynGAP+/−mice. Cofilin, an F-actin severing protein that is inactivated by phosphorylation, is a downstream target of a pathway regulated by Rac. We show that transient regulation of cofilin by treatment with NMDA is also disrupted in synGAP mutant neurons. Treatment of wild-type neurons with 25 μmNMDA triggered transient dephosphorylation and activation of cofilin within 15 s. In contrast, neurons cultured from mice with a homozygous or heterozygous deletion ofsynGAPlacked the transient regulation by the NMDA receptor. Depression of EPSPs induced by a similar treatment of hippocampal slices with NMDA was disrupted in slices fromsynGAP+/−mice. Our data show that synGAP mediates a rate-limiting step in steady-state regulation of spine morphology and in transient NMDA-receptor-dependent regulation of the spine cytoskeleton.
Personality in patients with pituitary adenomas is characterized by increased anxiety-related traits: comparison of 70 acromegalic patients with patients with non-functioning pituitary adenomas and age- and gender-matched controls
Authors: Sievers C , Ising M , Pfister H , Dimopoulou C , Schneider H J , Roemmler J , Schopohl J , Stalla G K
Published: December 2008

Objective

Although neuropsychiatric and morphological brain alterations in acromegalic patients have been described and a distinct disease personality is clinically suspected, this has never been systematically investigated. We examined whether patients with acromegaly showed an altered personality profile compared with patients with non-functioning pituitary adenomas and healthy controls.

Design and methods

In this cross-sectional study, 70 acromegalic patients and 58 patients with non-functioning pituitary adenomas were compared with 140 mentally healthy population controls, matched for age and gender. Personality traits were measured by standardized personality questionnaires (Eysenck personality questionnaire-RK and tridimensional personality questionnaire).

Results

Compared with healthy controls, acromegalic patients described themselves as distinctly more harm avoidant and neurotic and presented themselves with high social conformity. On harm avoidant subscales, they reported more anticipatory worries and pessimism, higher fear of uncertainty, higher fatigability and asthenia. This personality pattern was not specific for acromegaly, but could similarly be observed in patients with non-functioning pituitary adenomas. However, specific for patients with GH-producing adenomas was an even more reduced novelty-seeking behaviour, especially in terms of lower impulsiveness, compared with patients with non-functioning pituitary adenomas.

Conclusion

Patients with pituitary adenomas show a distinct pattern of increased anxiety-related personality traits compared with the general population, potentially as a result of the pituitary lesion and/or associated hormonal dysregulations and comorbidities. Acromegaly is additionally associated with reduced impulsivity and novelty-seeking behaviour, which might affect patients' management and their quality of life.
Protective effects of the cumulus-corona radiata complex during vitrification of horse oocytes
Authors: Tharasanit T , Colleoni S , Galli C , Colenbrander B , Stout T A E
Published: December 2008

Vitrifying oocytes is a potentially valuable means of preserving the female germ line, but significantly compromises oocyte developmental competence. This study examined the hypothesis that the cumulus complex protects the oocyte during vitrification. Vitrified-warmed immature cumulus oocyte complexes (COCs) were labelled with a plasma membrane impermeant DNA marker (ethidium homodimer-1) to examine the percentage and location of dead cumulus cells, and to investigate the effect of the proportion of dead cells (+1,+2 or +3) on the success ofin vitromaturation (IVM). Further, oocytes were labelled for connexin-43 or injected with Lucifer yellow dye to determine whether the integrity of the gap junctions between an oocyte and its cumulus was compromised by vitrification. Finally, the effect of denuding immature and mature oocytes on their ability to withstand vitrification was examined. Cryopreserving immature COCs increased the number of dead cumulus cells (13 vs 2.6% for controls;P<0.05). However, an increased proportion of dead cumulus cells did not affect post-warming maturation rates (∼30% MII) presumably because dead cells were located at the periphery of the cumulus mass and cumulus-oocyte gap junction communication was not disrupted. Moreover, cumulus removal prior to IVM or vitrification indicated that while the cumulus does protect immature oocytes during vitrification it does so by mechanisms other than support during maturation. Cumulus presence was also found to protect mature equine oocytes against vitrification-induced damage since cumulus-enclosed MII oocytes preserved their meiotic spindle quality better during vitrification than denuded oocytes (38.1 vs 3.1% normal spindles;P<0.05).
Silymarin in the treatment of chronic liver diseases: past and future
Authors: Fehér János , Lengyel Gabriella
Published: December 2008

Az idült májbetegségek kezelésére csak a kóroki folyamatok ismeretében tudunk célzott terápiát választani. Az oxidatív stressz okozta májkárosodásban (alkoholos és nem alkoholos májbetegség, gyógyszer és vegyszer okozta megbetegedések) az antioxidáns tulajdonságú szerek, mint például a silymarin, a vírusos eredetű krónikus hepatitisekben (hepatitis B- és hepatitis C-vírus-fertőzés) pedig a kombinált peginterferon + nukleozidanalóg kezelés az elsődlegesen választandó szer. A silymarin fő tulajdonságai: membránstabilizáló és antioxidáns hatás, elősegíti a májsejt-regenerációt, csökkenti a gyulladásos aktivitást és gátolja a fibrogenezist. Mindezt kísérletes és klinikai vizsgálatok is igazolták. Nyílt vizsgálatok szerint a silymarin tartós alkalmazása az alkoholos eredetű májcirrhosisban szenvedő betegek túlélési idejét jelentős mértékben növelte. Legújabban kimutatták, hogy nagy dózisú silibinininfúzió hepatitis C-vírus okozta krónikus hepatitisben négyhetes kezelés során jelentős mértékben csökkentette a hepatitis C-vírus-számot. A legújabb molekuláris biológiai vizsgálatok igazolták, hogy a silymarin, a fenti korábban bizonyított hatása mellett, jelentős mértékben képes csökkenteni a daganatossejt-proliferációt, az angiogenezist, valamint az inzulinrezisztenciát. Mindezen tulajdonságok alapján a mai korszerű betegellátásban a silymarinkészítmények alkalmazása a krónikus májbetegségek kezelésében, elsősorban az alkoholos és nem alkoholos steatohepatitisben, helyénvaló és várhatóan a jövőben is az lesz. Bizonyos tumoros betegségekben pedig adjuváns kezelésként kerülhetnek alkalmazásra.
O ensino-aprendizagem da relação médico-paciente: estudo de caso com esudantes do último semestre do curso de medicina
Authors: Grosseman Suely , Stoll Carolina
Published: December 2008

Tendo em vista a importância da relação médico-paciente nas dimensões técnica, humanística, ética e estética da prática médica, este estudo teve por objetivo conhecer como estudantes do último semestre do curso de Medicina de uma universidade federal do Sul do Brasil aprenderam a relação médico-paciente. Foi realizado estudo de caso de abordagem mista, por meio de entrevista semi-estruturada com 25 acadêmicos do universo de 47, selecionados aleatoriamente, por sorteio. Os aspectos percebidos como mais influentes no processo de ensino-aprendizagem da relação médico-paciente foram os bons e maus modelos, atendimentos realizados no dia-a-dia e relacionamentos interpessoais. As aulas sobre o tema foram consideradas escassas. Quinze estudantes (60%) referiram querer aprender mais sobre a relação médico-paciente durante o curso, em aulas com abordagem de situações específicas, tendo sido sugerida uma disciplina sobre o tema. Concluiu-se que o ensino-aprendizagem da relação médico-paciente poderia ser promovido pelo treinamento em habilidades de comunicação e pela criação de espaços para reflexão mediados por professores ou médicos ao longo do curso.
Material and human resources for neonatal resuscitation in public maternity hospitals in Brazilian state capitals
Authors: Almeida Maria Fernanda Branco de , Guinsburg Ruth , Costa José Orleans da , Anchieta Lêni Márcia , Freire Lincoln Marcelo Silveira
Published: December 2008

CONTEXT AND OBJECTIVE: In 2002, the early neonatal mortality rate in Brazil was 12.42 per thousand live births. Perinatal asphyxia was the greatest cause of neonatal death (about 23%). This study aimed to evaluate the availability of the resources required for neonatal resuscitation in delivery rooms of public hospitals in Brazilian state capitals. DESIGN AND SETTING: Multicenter cross-sectional study involving 36 hospitals in 20 Brazilian state capitals in June 2003. METHODS: Each Brazilian region was represented by 1-4% of its live births. A local coordinator collected data regarding physical infrastructure, supplies and professionals available for neonatal resuscitation in the delivery room. The information was analyzed using the Statistical Package for the Social Sciences, version 10. RESULTS: Among the 36 hospitals, 89% were referral centers for high-risk pregnancies. Each institution had a monthly mean of 365 live births (3% < 1,500 g and 15% < 2,500 g). The 36 hospitals had 125 resuscitation tables (3-4 per hospital), all with overhead radiant heat, oxygen and vacuum sources. Appropriate equipment for pulmonary ventilation was available for more than 90% of the 125 resuscitation tables. On average, one pediatrician, three nurses and five nursing assistants per shift worked in the delivery rooms of each institution. Out of the 874 pediatricians and 1,037 nursing personnel that worked in the delivery rooms of the 36 hospitals, 94% and 22%, respectively, were trained in neonatal resuscitation. CONCLUSIONS: The main public maternity hospitals in Brazilian state capitals have the resources to resuscitate neonates at birth.
Marginal grafts increase early mortality in liver transplantation
Authors: Bacchella Telesforo , Galvão Flávio Henrique Ferreira , Almeida José Luiz Jesus de , Figueira Estela Regina , Moraes Andreza de , Machado Marcel Cerqueira César
Published: December 2008

CONTEXT AND OBJECTIVE: Expanded donor criteria (marginal) grafts are an important solution for organ shortage. Nevertheless, they raise an ethical dilemma because they may increase the risk of transplant failure. This study compares the outcomes from marginal and non-marginal graft transplantation in 103 cases of liver transplantation due to chronic hepatic failure. DESIGN AND SETTING: One hundred and three consecutive liver transplantations to treat chronic liver disease performed in the Liver Transplantation Service of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo between January 2001 and March 2006 were retrospectively analyzed. METHODS: We estimated graft quality according to a validated scoring system. We assessed the pre-transplantation liver disease category using the Model for End-Stage Liver Disease (MELD), as low MELD (< 20) or high MELD (> 20). The parameters for marginal and non-marginal graft comparison were the one-week, one-month and one-year recipient survival rates, serum liver enzyme peak, post-transplantation hospital stay and incidence of surgical complications and retransplantation. The significance level was 0.05. RESULTS: There were no differences between the groups regarding post-transplantation hospital stay, serum liver enzyme levels and surgical complications. In contrast, marginal grafts decreased overall recipient survival one month after transplantation. Furthermore, low-MELD recipients of non-marginal grafts showed better one-week and one-month survival than did high-MELD recipients of marginal livers. After the first month, patient survival was comparable in all groups up to one year. CONCLUSION: The use of marginal graft increases early mortality in liver transplantation, particularly among high-MELD recipients.
THE GALACTOPOIETIC EFFECT OF IODINATED CASEIN: DOSE RESPONSE RELATIONSHIPS DURING PROLONGED TREATMENT
Authors: LEECH F. B.
Published: December 2008

1. In an experiment involving fifty-nine cows, the relative values were assessed of daily dosages of 15, 20 and 25 g. of iodinated casein incorporated in cattle cubes. Treatment was continued from 3 months after calving for 28 weeks, except on cows which went dry before this time.

2. The expected increase in milk yield lasted for 8 weeks, after which the response to the two lower doses quickly disappeared. The response to 25 g. of iodinated casein was maintained at a reduced level throughout the period of treatment.

3. The yield of butter fat reacted very similarly to milk yield.

4. There was no effect on the proportions of butter fat or of non-fatty solids in the milk.

5. Body weight was reduced by amounts proportional to the doses; this loss in weight gradually disappeared. After 12 weeks of treatment there were no significant differences between the groups.

6. There was no significant effect on the health of the cows or on their reproductive activity.
BLOOD CHANGES DURING THE ADAPTATION SYNDROME IN SHEEP
Authors: WHITE I. G.
Published: December 2008

1. The effect of twice-daily injections of formalin, as an agent eliciting the adaptation syndrome, has been studied on the blood constituents of sheep.

2. Within 4 days of the start of injections of 5 ml. of 4 % formalin there was a significant hypochloraemia, hypoglycaemia and leucocytosis with a return to normal levels after 10 days. There was also an intermediate compensatory hyperglycaemia. The leucocytosis was due primarily to a neutrophilia, although there was a slight transient increase in both absolute lymphocyte and eosinophil counts.

3. When the dose rate was increased to 10–20 ml. of 10% formalin, the plasma chloride and leucocyte patterns were repeated and there was also an increase in erythrocytes and haemoglobin values. In the later stages of the experiment the absolute lymphocyte and eosinophil counts were depressed, whilst the absolute monocyte count had risen.

4. There were no significant changes in blood acetone or in the basophil count throughout the experiment.

5. It is concluded that, in general, the blood changes elicited by an alarming stimulus in sheep are similar to those described in small laboratory animals. The renewed response to an increased intensity of stimulus observed in this experiment indicates that resistance is quantitatively as well as qualitatively specific.
EFFECTS OF ANDROSTENEDIONE AND PROGESTERONE ON OESTROUS SWELLING OF THE FERRET VULVA
Authors: HAMMOND J.
Published: December 2008

Quantitative data are given of the anti-oestrogenic action of progesterone on the vulva of the normal oestrous ferret, and the oöphorectomized animal treated with oestrogen implants. Initial experiments that suggested a similar action of androstenedione, such as has been reported on the mouse vagina, were not confirmed.

Amounts of androstenedione at least 80 times as great as those of progesterone that were effective in collapsing the normal oestrous vulva, and at least 10 times as great as those that antagonized the effect of oestrogen on the vulva and vaginal smear of the castrate, produced no effect.

In view of the different method of administration, among other factors, exact equality of relative anti-oestrogenic potency in mouse and ferret was not to be expected; but the observed difference suggests that androstenedione may be metabolized differently in the two species, the metabolites varying in anti-oestrogenic action.
ANTAGONISM OF VAGINAL ACTIONS OF OESTROGEN BY PROGESTERONE AND OTHER STEROIDS
Authors: ROBSON J. M. , SHARAF A. A.
Published: December 2008

The inhibition of the vaginal action of oestradiol and several synthetic oestrogens by progesterone, methyl testosterone and testosterone propionate have been studied quantitatively.

The action of the natural oestrogen is more easily inhibited than that of the synthetic oestrogens.
SERUM 'HORMONAL' IODINE IN RELATION TO THYROID FUNCTION AND TREATMENT WITH ADRENOCORTICOTROPHIC HORMONE (ACTH)
Authors: SALTER W. T. , ROSENBLUM I.
Published: December 2008

The calibration and application of a catalytic method for serum and tissue iodine is described. The apparatus is simple, multiple determinations can be performed simultaneously, and the answer read directly from a spectrophotometer scale. For routine work with human serum in the clinic, 0·5 ml. samples are used. The values so obtained conform closely to those obtained by distillation procedures employing larger samples. Large pools of human serum yield a value of 5·3 μg. iodine/100 ml. (protein-bound). The arbitrary 'normal' range of values is the same as for other methods, i.e. approximately 4–8 μg./100 ml. The method is also applicable to decigram samples of fresh tissue.

The effect of treatment with adrenocorticotrophic hormone (ACTH) upon circulating thyroid hormone is illustrated in several clinical cases, i.e. acromegaly, the nephrotic syndrome, scleroderma and Cushing's syndrome.
THE ASSAY OF EXTRACTS OF SUPRARENAL GLAND PRIOR TO THEIR USE IN THE TREATMENT OF ADRENAL INSUFFICIENCY
Authors: LOCKETT MARY F.
Published: December 2008

Details are given of a technique by which the mineralocorticoid content of extracts of suprarenal cortex may be assayed in adrenalectomized dogs, with an accuracy of ±5%. The power of these extracts to maintain life in adrenalectomized animals is simultaneously tested. The results of the assay become available in 12–14 days.
THE URINARY EXCRETION OF PREGNANE-3α:20α-DIOL IN THE FEMALE RABBIT IMMEDIATELY AFTER MATING
Authors: VERLY W. G.
Published: December 2008

The transient excretion of pregnane-3α:20α-diol in the urine of female rabbits after mating is derived from progesterone liberated from the ovary.
SEBACEOUS GLANDS
Authors: EBLING F. J.
Published: December 2008

As studied in samples of dorsal skin taken at biopsy and measured by sebaceous cell counts, the sebaceous alveoli of immature female rats increased in size for 2 days after the implantation of 1 mg. of oestradiol benzoate, and decreased progressively on days 3, 5 and 9 to a level much below normal on day 20. This was accompanied by an increase in size of the sebaceous cells which was evident by the first day after implantation. There was no subsequent decrease in size below normal. Changes in alveolar number may also have taken place.

Wounding appeared to increase the size of the sebaceous glands for a distance of at least 2–8 mm. from the edge of the wound, and this effect was apparent even 1 day after wounding.
THE ACTION OF GLYCINE ON THE LIVER GLYCOGEN OF FASTING MICE, NORMAL AND ADRENALECTOMIZED
Authors: LOCKETT MARY F. , EVANS MARY M.
Published: December 2008

The effects of injected glycine on the liver glycogen of fasting normal and adrenalectomized mice have been compared with those of injected glucose.

In both normal mice and cortisone-treated adrenalectomized mice glycine caused significant reduction in hepatic glycogen (Table 1).

In salt-maintained and in DOCA-treated adrenalectomized mice,glycine hada glycogen-sparing action, equivalent, carbon for carbon, to that of glucose.

These observations are related to the influence of C 11 oxygenated adrenal steroids on protein metabolism.
SOME EFFECTS OF ADMINISTERING 'ANTI-THYROXINE' COMPOUNDS TO RATS
Authors: LAWSON A. , SEARLE C. E.
Published: December 2008

A number of thyroxine analogues have been administered to rats, and their effect on the uptake of radioactive iodine has been investigated. The marked depressions nearly always obtained can in many cases be attributed to iodide liberated by decomposition of the drugs. A marked sex difference was observed with certain compounds.

In long-term experiments in which the drugs were incorporated in the diet alone or together with thiouracil, the growth rate, thyroid weight and thyroid total iodine were determined.
STUDIES ON THE HORMONAL INDUCTION OF MAMMARY GROWTH AND LACTATION IN THE GOAT
Authors: COWIE A. T. , FOLLEY S. J. , MALPRESS F. H. , RICHARDSON K. C.
Published: December 2008

Extensive morphological and functional investigations have been carried out on the artificial induction of mammary development and lactation in the goat using hexoestrol alone and in combination with progesterone, at several dose levels and proportions. Administration of the oestrogen and progesterone was either by tablet implantation or by subcutaneous injection in oily solution. Forty animals were used, of which twenty-three were ovariectomized during infancy. Special histological techniques were devised for studying and estimating quantitatively the degree of mammary development. In the later experiments this was achieved by surgically removing one half of the udder, i.e. one gland, when the lactation curve had reached a maximum. In three normally lactating goats the operation had no influence on the milk yield of the remaining gland.

For the dose levels used, the milk yields of the animals receiving oestrogen and those receiving oestrogen and progesterone did not differ significantly. In general, the artificially induced milk yields were below the expected yields had the animals come into lactation after kidding.

It appeared highly probable that the total area of secretory epithelium in the artificially developed gland was less than in the normally developed udder. A high correlation was observed between the surface area of the secretory epithelium in the entire half udder and the milk yield.

Several marked abnormalities were observed in the microscopic structure of the udders. These were less evident in the glands of the goats receiving progesterone provided the oestrogen dose was not excessive.
THE MILK-EJECTING ACTIVITY OF EXTRACTS OF THE POSTERIOR PITUITARY GLAND
Authors: WHITTLESTONE W. G.
Published: December 2008

The lactating sow milked mechanically has been used for the study of the hormones of the posterior pituitary gland. The van Dyke protein and du Vigneaud's high potency posterior lobe oxytocic polypeptide have been shown to possess milk-ejecting activity equivalent to their oxytocic activity. Commercial pressor preparations and du Vigneaud's highly purified vasopressin have milk-ejecting activity corresponding to a given pressor activity which is equivalent to one-fifth of the same number of oxytocic units.
THE EFFECTS OF THYROXINE AND THIOURACIL ON THE TUBERCULIN REACTIONS OF GUINEA-PIGS
Authors: LEECH F. B. , PATERSON A. B.
Published: December 2008

Three groups of twelve guinea-pigs were selected from a batch inoculated with a live culture of BCG. Two of these groups were selected for treatment with thyroxine and thiouracil. The third served as untreated controls. The experiment was divided into three periods; in the first, groups I and III received thyroxine and thiouracil respectively; in the second, all drug treatment was discontinued; in the third, the treatments were reversed, thiouracil being given to group I and thyroxine to group III. All guinea-pigs were injected intradermally with OT and PPD tuberculins at the end of the first and third periods; the diameters of the 24 hr. lesions were analysed by the appropriate statistical methods.

Thyroxine and thiouracil had opposite effects on the reactions to PPD tuberculin, the former depressing the average response. Effects on the reactions to OT were irregular. There were no significant effects on the fresh weights of the adrenal glands.
EFFECTS OF SOME WATER SOLUBLE STEROIDS ON THE UTERUS
Authors: ROBSON J. M. , SHARAF A. A.
Published: December 2008

The effects of disodium oestradiol disulphate, sodium oestrone sulphate, testosterone sulphate and strophanthin on the mouse, rabbit, rat and human uterus in vitro have been investigated. All the sex hormone derivatives produced qualitatively similar effects which appear to depend on the hormonal environment of the uterus. Strophanthin consistently produced a motor effect.
THE ACTION AND FATE OF VASOPRESSIN IN NEWBORN AND INFANT RATS
Authors: HELLER H.
Published: December 2008

Estimations of urine volumes and inulin U/P ratios in newborn rats after the administration of 4·5 ml. water and 10 mU. vasopressin/100 g. body weight failed to show an antidiuretic response comparable to that produced in adult controls. When body surface was chosen as the basis of dosage, relatively larger amounts of water were given to newborn rats. These produced an increase in the rate of urine flow (which, however, still remained well below the adult level), but an inhibitory effect of vasopressin again could not be demonstrated.

Experiments on older rats (up to 4 weeks of age) showed that an antidiuretic effect of vasopressin comparable to that of adults develops only after several weeks of postnatal life, approximately at the same time as a full diuretic response to water could be obtained.

When 10 mU. vasopressin/100 g. body weight was injected both adult and newborn rats excreted about 10% of this dose.

It is suggested that vasopressin acts less effectively in newborn rats because for some time after birth the kidney is less responsive to the posterior pituitary antidiuretic hormone than in adults.
MECHANISM OF THE CHROMATOPHOROTROPHIC EFFECT OF ACTH
Authors: SULMAN F. G.
Published: December 2008

The chromatophorotrophic effect of ACTH which, in the Addisonian patient does not require the presence of the adrenal glands, has been studied in the tree frog (Hyla arborea).

Frog skin in vitro gave the chromatophorotrophic effect with solutions of ACTH. Slight reactions were produced by intermedin, pitressin and pitocin, while fifteen other hormones and thirty-eight amines gave negative reactions. There was a conspicuous difference between the effective concentration of ACTH in vivo and in vitro, the doses required for the in vitro effect being about a thousand times higher.

Adrenalectomized, hypophysectomized, as well as intact frogs showed the full chromatophorotrophic effect.
THE EFFECT OF COMPLETE ADRENALECTOMY ON THE WALLABY (SETONYX BRACHYURUS)
Authors: BUTTLE JENNIFER M. , KIRK R. L. , WARING H.
Published: December 2008

1. Data are presented on the survival time of the wallaby, Setonyx brachyurus (Quoy & Gaimard), subjected to double adrenalectomy in a two-stage operation. Animals maintained on a normal diet after the second operation had a mean survival time of 36 hr. Treatment with 1% saline, injections of whole cortical extract, and of deoxycorticosterone acetate increased the mean survival time to 91, 83 and 108 hr. respectively, but did not maintain life indefinitely.

2. The typical symptoms following the removal of the second adrenal were increasing anorexia, muscular weakness and eventual collapse, with convulsive seizures during the collapsed state in some cases.

3. Determinations of plasma sodium and potassium values showed a marked decline in plasma sodium, and a rapid rise in plasma potassium during the terminal stages. Blood glucose generally fell to low levels, while chloride fell sharply in some cases and tended to rise and then fall again in others.

4. These results are compared with the findings reported on the American opossum, Didelphis virginiana.
THE COMPARATIVE POTENCY OF NATURAL AND SYNTHETIC OESTROGENS IN THE RHESUS MONKEY
Authors: ECKSTEIN P. , KROHN P. L. , ZUCKERMAN S. , HEALY M. J. R.
Published: December 2008

1. The minimum amount of oestrogen, given as a single intramuscular injection, that is required to induce oestrogen withdrawal uterine bleeding ('threshold dose') has been estimated for eleven oestrogens in twenty-five spayed adolescent or mature rhesus monkeys (Macaca mulatta).

2. The threshold dose was always smaller when it was approached from supra-threshold dosage levels (falling series) than from sub-threshold levels (rising series).

3. The oestrogens tested can be arranged in the following decreasing order of potency: oestradiol dipropionate, stilboestrol dipropionate, oestradiol caprylate, oestradiol benzoate, oestradiol benz-butyrate, oestrone benzoate, stilboestrol, hexoestrol, oestradiol, oestrone, dienoestrol.

4. Esterification of the oestrogens increased the potency and duration of bleeding, but diminished the latent interval between the injection and the onset of bleeding.

5. Latency before bleeding was shorter, and duration of bleeding was longer the more potent the oestrogen.

6. The latent interval before bleeding was shorter for falling series of injections than for rising series of injections.

7. At doses above the threshold, latency before bleeding and duration of bleeding tended to become shorter.