bluuebunny/crossref_metadata_2025 huggingface dataset:
Age Effects on the Reactivity of Antistreptococcal Cell Membrane Antisera to Murine Glomerular Basement Membrane
Authors: Lange C.F. , Weber Maria , Nayyar R.P.
Published: November 2008

Antisera to the streptococcal cell membrane (SCM) were evaluated for their reactivity to murine glomerular basement membrane (GBM) in four strains of mice. Animals were studied on a daily basis from birth through 3 months and weekly thereafter through 18 months. Paired animals were compared for in vivo binding of antibody versus an indirect fluorescent antibody technique on fresh kidney sections. The findings demonstrated a granular type GBM staining for all anti-SCM which were positive. Nonspecific background staining accompanied most of the indirect fluorescent antibody sections tested while being totally absent for the direct fluorescent test on tissue from in vivo challenge of the primary antibody. The in vitro testing showed tissue from young mice (0–6 days old) to be most reactive, while the strongest reactivity was seen in the age group of 10–20 days for in vivo testing. These cross-reactive antibodies, i.e., GBM-binding anti-SCM, are best evaluated by in vivo methods where tissue is taken 4 days after antiserum injection. Animals of the age range 6–8 weeks were often negative, indicating that this age range selected for many studies may not be the most favorable one via either in vitro or in vivo studies.
Biphasic Alteration of Renin-Angiotensin-Aldosterone System in Streptozotocin-Diabetic Rats
Authors: Kikkawa Ryuichi , Kitamura Eisaku , Fujiwara Yoshihiko , Haneda Masakazu , Shigeta Yukio
Published: November 2008

The alteration of renin-angiotensin-aldosterone system caused by diabetes mellitus was studied in streptozotocin-diabetic rats. The plasma renin activity (PRA), and plasma levels of angiotensin II (A II) and aldosterone (PAC) were measured in diabetic and age-matched control rats in 1, 2, 4 and 8 weeks after the intravenous injection of streptozotocin (50mg/kg body weight). Diabetic rats showed the marked hyperglycemia persistently throughout the experimental period. On 1 st week PRA, A II and PAC were significantly increased, and A II and PAC were also significantly elevated on 2nd week in diabetic rats compared with control rats. However, on 4th and 8th weeks PRA, A II and PAC in diabetic rats were significantly lower than those of control rats. Hematocrit values in diabetic rats were elevated on 1st week, normalized on 2nd and 4th weeks and then decreased on 8th week. These results may suggest that the hyperglycemia causes a biphasic alteration of renin-angiotensin-aldosterone system, i.e., early stimulated state due to volume depletion and later suppressed state due to volume expansion.
Macula Densa Control of Renin Secretion and Glomerular Vascular Tone: Evidence for Common Cellular Mechanisms
Authors: Briggs Josephine P. , Schnermann Jurgen
Published: November 2008

The macula densa is believed to function as a sensor for control of intrarenal vascular tone and renin secretion. Increases in flow rate through the loop of Henle or increases in distal tubular fluid NaCl concentration result in an increase in local vascular tone and a decrease in glomerular filtration rate, the tubuloglomerular feedback (TGF) mechanism. Increases in distal NaCl concentration are also believed to inhibit renin secretion. Evidence will be reviewed that suggests that these two processes may be activated concurrently and may share common cellular mechanisms. Similarities in the sensor step include a similar pattern of ion specificity, with both responses being relatively anion specific but showing little cation specificity. TGF responses are inhibitable by furosemide, and the renin secretion produced by furosemide seems to be in part macula densa dependent. There appear also to be common features in the effector step of both responses. Increases in intracellular calcium are implicated in both the vasoconstrictive response seen with increased macula densa NaCl concentration and in inhibition of renin secretion. Changes in cyclic AMP may play a role in the converse responses.
Effect of Gentamicin on Urinary Acidification in the Rat
Authors: Silva Costa , Gil Zaladek , Nascimento G. , Cavanal M.F.
Published: November 2008

The effect of gentamicin, an aminoglycoside antibiotic, on renal function and especially on acid excretion was studied in normal and acidotic rats. The doses used were 1 (G4) and 10 (G40) times the suggested human therapeutic dose on a weight basis. After 10 days of each treatment, the glomerular filtration rate (GFR) was unchanged in G4 but fell significantly (p < 0.05) in G40. In the acidotic groups (AG4 and AG40) there was an accentuated reduction in GFR, renal plasma flow and urine/plasma inulin ratio. Normal rats showed a normal acid excretion even with the high-dose treatment but, in the acidotic group, there was a significant decrease in ammonia excretion. The amount of bicarbonate excretion was significantly elevated in those groups, leading to a greater urinary pH. These results indicate that acute metabolic acidosis enhanced the nephrotoxic effects of gentamicin and impaired the excretion of an acid overload.
Immunocytochemical Study of Glutathione Peroxidase in Normal Rat Kidney
Authors: Mizuiri Sonoo , Hirata Kiyofumi , Izumi Shinichi , Komatsu Noriyuki , Yoshimura Shinichi , Watanabe Keiichi
Published: November 2008

In the normal rat kidney, immunohistochemical localization of glutathione peroxidase (GSH-Po) was mainly in the proximal tubules (PTs), where the proximal portions (S1+S2) were more intensely stained than the distal portion (S3). Immunocytochemically, GSH-Po was localized in cytosol including the core of microvilli and lysosomes of the epithelial cells in the PTs. Since albumin and IgG were not found in cytosol, it is suggested that cytosolic GSH-Po may be generated in situ, but is not derived from the serum.
Effective Hydraulic Permeability of the Glomerular Capillary Wall in Rats after Uninephrectomy
Authors: Neumann Klaus H. , Schurek Hans-Joachim , Kellner Christian , Kühn Karlwilhelm , Aeikens Bernhard
Published: November 2008

The effective hydraulic permeability (k) of glomerular capillaries was studied in 2-month-old Wistar rats 4 weeks after uninephrectomy in comparison to age-matched control rats. Isolated kidneys were perfused with a cell-free solution containing 5% albumin. In this preparation the rise of colloid osmotic pressure along the glomerular capillaries can be neglected because the filtration fraction is low (3%) due to high perfusion rates at normal filtration rates. Single nephron filtration rates (SNGFR) and effective filtration pressures were estimated by micropuncture to calculate the ultrafiltration coefficient (Kf). Glomerular capillary surface area was measured morphometrically to obtain k (k = Kf/S). We found that the effective hydraulic permeability in uninephrectomized rats was higher than in rats of comparable age (26.0 vs 18.0 nl/mm Hg · s · cm2). This can contribute to the adaptive rise in SNGFR after uninephrectomy.
Morphological Changes in the Renal Macula densa During Natriuresis and Diuresis
Authors: Alcorn D. , Anderson W.P. , Ryan G.B.
Published: November 2008

Morphological changes in the macula densa have been studied during the infusion of diuretic agents into the renal artery of anesthetized dogs. The kidneys were fixed by rapid high pressure perfusion with glutaraldehyde. Large basolateral intercellular spaces were seen between macula densa cells in control kidneys, but the number and extent of these spaces were strikingly reduced during the natriuresis and diuresis induced by the infusion of frusemide, ethacrynic acid or mannitol. Natriuresis and diuresis produced by the intravenous infusion of large volumes of 0.9% NaCl solution also resulted in closure of these spaces. No simple relationship existed between changes in plasma renin activity and closure of the spaces between macula densa cells during these procedures. A distinctive, membrane-bound, vesicle-containing structure was identified between the basolateral processes of the cells of each macula densa; the function of this structure awaits elucidation. We suggest that changes in the size of the basolateral intercellular spaces of the macula densa reflect changes in fluid flux between the distal tubule and the interstitium of the juxtaglomerular apparatus.
Diabetes insipidus with Renal Resistance to Vasopressin in the Desoxycorticosterone-Treated Dog: A Possible Role for Prostaglandins
Authors: Gullner Hans-Georg , West David , Gill, Jr. John R. , Robertson Gary L.
Published: November 2008

We examined the release of vasopressin and the renal response to exogenous vasopressin before and during desoxycorticosterone acetate (DOCA) administration in the dog. As treatment with DOCA produced potassium loss, urine volume increased, urinary osmolality decreased, and urinary PGE2 tended to increase. The increase in urine volume was accompanied by increases in serum sodium, in plasma osmolality and in plasma arginine vasopressin. The threshold for vasopressin release measured during polyuria was higher than control but the rate of vasopressin release was unchanged. The DOCA-induced polyuria was not affected by treatment with vasopressin which further increased plasma vasopressin. Treatment with indomethacin which corrected the increase in urinary PGE2 excretion but not the hypokalemia, restored the renal responsiveness to vasopressin, decreased the secretion of vasopressin, and corrected the polyuria and the hypernatremia. These findings suggest that DOCA-induced polyuria is attributable to a decrease in renal responsiveness to vasopressin which may be mediated in part by an increase in the renal synthesis of prostaglandins.
Hemodynamics of the Recently Opened Glomeruli
Authors: Heller Jiří , Horáček Vladislav
Published: November 2008

In 22- to 26-day-old beagle puppies, just after superficial nephrons have begun to function, the single nephron glomerular filtration rate is extremely low (6.7nl·min-1) approximating a tenth of the adult value (5 7 nl min-1) even though blood pressure is as high as 90 mm Hg. Glomerular vascular resistance is almost six times the value found in the adult dog (1.8 vs. 0.32 mm Hg· ml-1 min), this increase being mainly due to a rise in afferent (80%) rather than in efferent (20%) resistance. The glomerulus, having only recently started to function, is characterized by filtration pressure equilibrium, a phenomenon atypical of superficial glomeruli in the adult dog. These findings favor the concept that a low glomerular blood flow rate might be the main cause of the very low SNGFR in the new glomeruli, although some contribution of an altered ultrafiltration coefficient cannot be excluded.
Carbonic Anhydrase Inhibitors
Authors: Preisig P.A. , Toto R.D. , Alpern R.J.
Published: November 2008

The purpose of the present review is to describe the use of carbonic anhydrase inhibitors in clinical medicine and renal physiology. We first describe the localization of carbonic anhydrase within the kidney and then discuss evidence for its role in renal acidification and NaCl absorption. This is then followed by a description of clinical uses for carbonic anhydrase inhibitors. Many of the uses and effects of carbonic anhydrase inhibitors can be predicted from an understanding of renal physiology and the role of carbonic anhydrase. The limited potency of carbonic anhydrase inhibitors correlates well with the large magnitude of carbonic anhydrase-independent bicarbonate absorption. While theories for carbonic anhy-drase-independent bicarbonate absorption are presented, the exact mechanisms remain unresolved.
Effect of Acidosis and Alkalosis on Divalent Ion Transport across the Proximal Straight Tubule of the Rabbit
Authors: Wong Norman L.M. , Dirks John H.
Published: November 2008

In vitro microperfusion experiments were performed on the cortical proximal straight tubule of the rabbit to examine the effect of acid base disturbances on calcium and magnesium transport by this segment of the nephron. During acidosis (pH 7.22 ± 0.01) net calcium reabsorption was reduced, whereas during alkalosis (pH 7.82 ± 0.02) net calcium reabsorption was increased. Our flux experiments with 45Ca indicate that the efflux of Ca from the lumen to the bath remained the same during acidosis; however, the back-flux (bath to lumen) of calcium increased. On the other hand, during alkalosis the efflux of calcium rose and the influx of calcium remained unchanged. These changes in fluxes during acid-base disturbances can be accounted for mainly by changes in ionized calcium as a result of pH changes. We failed to observe any effect of acid-base changes on net magnesium transport by the superficial proximal straight tubule.
Renovascular Effects of Adenosine Receptor Agonists
Authors: Holz Frank G , Steinhausen Michael
Published: November 2008

The purpose of the present experiments was to determine the renovascular effects of the adenosine agonists N-ethyl-carboxamide adenosine (NECA), N6-cyclohexyl adenosine (CHA) and 2-chloro adenosine (2-CLA). The diameter of pre- and postglomerular vessels in the split hydronephrotic kidney of Inactin®-anesthetized rats was measured by in vivo television microscopy. All metabolically stable adenosine agonists were topically applied into the renal tissue bath. NECA, a preferential A2 adenosine receptor agonist, induced dose-dependent marked pre- and slight postglomerular vasodilation except for a small constrictory effect on the afferent arteriole near the glomerulus. Application of CHA, a selective A1 adenosine receptor agonist, led to a vasoconstriction of all preglomerular vessels, the extent of which was greatest at the most distal segment of the afferent arteriole. 2-CLA, a nonselective agonist, produced a small decrease in diameter in all preglomerular vessels, a marked constriction of the afferent arteriole at sites near the glomerulus, and a slight dilation of postglomerular vessels. Glomerular blood flow (GBF) was increased by NECA, and decreased by CHA and 2-CLA. The effects of CHA in reducing GBF were greater than those of 2-CLA. From these experiments it is concluded that vascular A1and A2 adenosine receptors are present in the kidney and that activation of A1 receptors is associated with preglomerular vasoconstriction only, whereas activation of A2 receptors mediates pre- and postglomerular vasodilation with a lack of vasodilatory response of the distal afferent arteriole. Furthermore, these data indicate that nonselective occupation of both receptor subclasses is associated with marked vasoconstriction of the afferent arteriole and little vasodilation of the efferent arteriole.
Effect of Maleate on Tubular Protein Reabsorption in Dog Kidneys
Authors: Hysing Jan , Østensen Jonny , Tolleshaug Helge , Kiil Fredrik
Published: November 2008

To examine the effects on protein and electrolyte reabsorption of reducing the energy supply to the proximal tubules, an inhibitor of the citric acid cycle, maleate (600 mg · kg-1), was administered to anesthetized dogs during continuous ethacrynic acid infusion. One hour after infusion, maleate reduced renal oxygen consumption from 128 ± 3 to 48 ± 6 µmol·min-1. Comparisons at similar GFR showed that maleate reduced bicarbonate reabsorption by 65%, chloride reabsorption by 60% and phosphate reabsorption by 90%. Tubular reabsorption of lysozyme, determined by the ‘trapped-label’ method, was reduced by 97%. Total protein excretion in urine increased from 0.12 to 1.0 mg·min-1 and was not associated with a significant increase in brush border and lysosome marker enzymes. However, by superimposing a carbonic anhydrase inhibitor, acetazolamide (100 mg·kg-1), electrolyte reabsorption was slightly further reduced but protein excretion increased to 2.7 mg·min-1, coincidentally with a dramatic increase in enzyme excretion: approximately 20-fold in the brush border enzymes, alanine aminopeptidase and alkaline phosphatase, and 10-fold in the lysosomal enzymes, acid phosphatase and N-acetyl-β-glucosaminidase. Our data indicate that maleate stops protein reabsorption without signs of acute tubular damage, whereas subsequent administration of acetazolamide results in tubular desquamation and albumin leakage.
Transient Increase in Plasma Oxidized LDL During the Progression of Atherosclerosis in Apolipoprotein E Knockout Mice
Authors: Kato Rina , Mori Chihiro , Kitazato Keiko , Arata Satoru , Obama Takashi , Mori Masahiro , Takahashi Katsuhiko , Aiuchi Toshihiro , Takano Tatsuya , Itabe Hiroyuki
Published: November 2008

Background—

Plasma level of oxidized low-density lipoprotein (OxLDL) is a risk marker for cardiovascular diseases. The behavior of plasma OxLDL before disease progression has not been studied previously.

Methods and Results—

In this study, we developed a sensitive ELISA procedure for detecting mouse circulating OxLDL using a monoclonal antibody that recognizes oxidized phosphatidylcholine and a rabbit antimouse apolipoprotein B-48 polyclonal antibody. Apolipoprotein E knockout mice were fed on a chow diet for 40 weeks. Oil red O–positive lesions developed gradually by 20 weeks, and the percentage area covered by the lesions increased dramatically after 28 weeks; it covers 33.4% of the surface area by 40 weeks. The OxLDL level, measured after LDL fraction was isolated from each mouse, at 10 weeks was 0.015 ng/μg LDL. It increased 3-fold at 20 weeks of age and then decreased to the basal level by 40 weeks of age, suggesting that OxLDL appears before the development of atherosclerotic lesions. The occurrence of lipid peroxidation products, acrolein and oxidized phosphatidylcholines, in aortic tissue were revealed by immunohistochemical staining as early as 10 weeks.

Conclusion—

These results suggest that OxLDL might be involved in the early stages of progression of atherosclerotic lesions.
Blockade of Bradykinin Receptor B1 but Not Bradykinin Receptor B2 Provides Protection From Cerebral Infarction and Brain Edema
Authors: Austinat Madeleine , Braeuninger Stefan , Pesquero João B. , Brede Marc , Bader Michael , Stoll Guido , Renné Thomas , Kleinschnitz Christoph
Published: November 2008

Background and Purpose—

Brain edema is detrimental in ischemic stroke and its treatment options are limited. Kinins are proinflammatory peptides that are released during tissue injury. The effects of kinins are mediated by 2 different receptors (B1 and B2 receptor [B1R and B2R]) and comprise induction of edema formation and release of proinflammatory mediators.

Methods—

Focal cerebral ischemia was induced in B1R knockout, B2R knockout, and wild-type mice by transient middle cerebral artery occlusion. Infarct volumes were measured by planimetry. Evan’s blue tracer was applied to determine the extent of brain edema. Postischemic inflammation was assessed by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. To analyze the effect of a pharmacological kinin receptor blockade, B1R and B2R inhibitors were injected.

Results—

B1R knockout mice developed significantly smaller brain infarctions and less neurological deficits compared to wild-type controls (16.8±4.7 mm
3
vs 50.1±9.1 mm
3
, respectively;
P
<0.0001). This was accompanied by a dramatic reduction of brain edema and endothelin-1 expression, as well as less postischemic inflammation. Pharmacological blockade of B1R likewise salvaged ischemic tissue (15.0±9.5 mm
3
vs 50.1±9.1 mm
3
, respectively;
P
<0.01) in a dose-dependent manner, even when B1R inhibitor was applied 1 hour after transient middle cerebral artery occlusion. In contrast, B2R deficiency did not confer neuroprotection and had no effect on the development of tissue edema.

Conclusions—

These data demonstrate that blocking of B1R can diminish brain infarction and edema formation in mice and may open new avenues for acute stroke treatment in humans.
A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicity
Authors: Weldon John E. , Xiang Laiman , Chertov Oleg , Margulies Inger , Kreitman Robert J. , FitzGerald David J. , Pastan Ira
Published: November 2008

Immunotoxins based on Pseudomonas exotoxin A (PE) are promising anticancer agents that combine a variable fragment (Fv) from an antibody to a tumor-associated antigen with a 38-kDa fragment of PE (PE38). The intoxication pathway of PE immunotoxins involves receptor-mediated internalization and trafficking through endosomes/lysosomes, during which the immunotoxin undergoes important proteolytic processing steps but must otherwise remain intact for eventual transport to the cytosol. We have investigated the proteolytic susceptibility of PE38 immunotoxins to lysosomal proteases and found that cleavage clusters within a limited segment of PE38. We subsequently generated mutants containing deletions in this region using HA22, an anti-CD22 Fv-PE38 immunotoxin currently undergoing clinical trials for B-cell malignancies. One mutant, HA22-LR, lacks all identified cleavage sites, is resistant to lysosomal degradation, and retains excellent biologic activity. HA22-LR killed chronic lymphocytic leukemia cells more potently and uniformly than HA22, suggesting that lysosomal protease digestion may limit immunotoxin efficacy unless the susceptible domain is eliminated. Remarkably, mice tolerated doses of HA22-LR at least 10-fold higher than lethal doses of HA22, and these higher doses exhibited markedly enhanced antitumor activity. We conclude that HA22-LR advances the therapeutic efficacy of HA22 by using an approach that may be applicable to other PE-based immunotoxins.
Expression of BLIMP1/PRMT5and concurrent histone H2A/H4 arginine 3 dimethylation in fetal germ cells, CIS/IGCNU and germ cell tumors
Authors: Eckert Dawid , Biermann Katharina , Nettersheim Daniel , Gillis Ad JM , Steger Klaus , Jäck Hans-Martin , Müller Annette M , Looijenga Leendert HJ , Schorle Hubert
Published: November 2008

Background

Most testicular germ cell tumors arise from intratubular germ cell neoplasia unclassified (IGCNU, also referred to as carcinoma in situ), which is thought to originate from a transformed primordial germ cell (PGC)/gonocyte, the fetal germ cell. Analyses of the molecular profile of IGCNU and seminoma show similarities to the expression profile of fetal germ cells/gonocytes. In murine PGCs, expression and interaction of Blimp1 and Prmt5 results in arginine 3 dimethylation of histone H2A and H4. This imposes epigenetic modifications leading to transcriptional repression in mouse PGCs enabling them to escape the somatic differentiation program during migration, while expressing markers of pluripotency.

Results

In the present study, we show that BLIMP1 and PRMT5 were expressed and arginine dimethylation of histones H2A and H4 was detected in human male gonocytes at weeks 12–19 of gestation, indicating a role of this mechanism in human fetal germ cell development as well. Moreover, BLIMP1/PRMT5 and histone H2A and H4 arginine 3 dimethylation was present in IGCNU and most seminomas, while downregulated in embryonal carcinoma (EC) and other nonseminomatous tumors.

Conclusion

These data reveal similarities in marker expression and histone modification between murine and human PGCs. Moreover, we speculate that the histone H2A and H4 arginine 3 dimethylation might be the mechanism by which IGCNU and seminoma maintain the undifferentiated state while loss of these histone modifications leads to somatic differentiation observed in nonseminomatous tumors.
Transmission potential, skin inflammatory response, and parasitism of symptomatic and asymptomatic dogs with visceral leishmaniasis
Authors: Verçosa BLA , Lemos CM , Mendonça IL , Silva SMMS , de Carvalho SM , Goto H , Costa FAL
Published: November 2008

Background

Visceral leishmaniasis in Brazil is caused by the protozoanLeishmania (Leishmania) chagasiand it is transmitted by sandfly of the genusLutzomyia. Dogs are an important domestic reservoir, and control of the transmission of visceral leishmaniasis (VL) to humans includes the elimination of infected dogs. However, though dogs are considered to be an important element in the transmission cycle ofLeishmania, the identification of infected dogs representing an immediate risk for transmission has not been properly evaluated. Since it is not possible to treat infected dogs, they are sacrificed when a diagnosis of VL is established, a measure that is difficult to accomplish in highly endemic areas. In such areas, parameters that allow for easy identification of reservoirs that represents an immediate risk for transmission is of great importance for the control of VL transmission. In this study we aimed to identify clinical parameters, reinforced by pathological parameters that characterize dogs with potential to transmit the parasite to the vector.

Results

The major clinical manifestations of visceral leishmaniasis in dogs from an endemic area were onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. The transmission potential of these dogs was assessed by xenodiagnosis usingLutzomyia longipalpis. Six of nine symptomatic dogs were infective toLutzomyia longipalpiswhile none of the five asymptomatic dogs were infective to the sandfly.Leishmaniaamastigotes were present in the skin of all clinically symptomatic dogs, but absent in asymptomatic dogs. Higher parasite loads were observed in the ear and ungueal region, and lower in abdomen. The inflammatory infiltrate was more intense in the ears and ungueal regions of both symptomatic and asymptomatic dogs. In clinically affected dogs in which few or noneLeishmaniaamastigotes were observed, the inflammatory infiltrate was constituted mainly of lymphocytes and macrophages. When many parasites were present, the infiltrate was also comprised of lymphocytes and macrophages, as well as a larger quantity of polymorphonuclear neutrophils (PMNs).

Conclusion

Dogs that represent an immediate risk for transmission ofLeishmaniain endemic areas present clinical manifestations that include onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. Lymphadenopathy in particular was a positive clinical hallmark since it was closely related to the positive xenodiagnosis.
Béla Bartók’s Arab music research and composition
Authors: Parker Sylvia
Published: November 2008

In 1913 Béla Bartók traveled to Algeria to research Arab folk music. He took with him the most modern technological device then available, the Edison phonograph, and recorded Arab peasants performing their music. Analysis of his ensuing scholarly documentation and free composition reveals the inspiration Bartók drew from Arab folk music, not only in his treatment of traditional musical elements — melody, rhythm, and harmony — but also in novel incorporation of exotic timbre, scales, drum modes, ululation, and exorcism. This paper elucidates diverse musical elements with examples from authentic folk music and Bartók’s compositions. What emerges is a remarkably comprehensive image of Arab music, seen through the lens of Béla Bartók’s unique scholarship and creativity.
Dynamic Cost-Effectiveness: A More Efficient Reimbursement Criterion
Authors: Lundin Douglas , Ramsberg Joakim
Published: November 2008

Basing drug reimbursement on cost-effectiveness provides too little incentives for R&D. The reason for this is that cost-effectiveness is concerned with immediate value for money. But since the price of a drug usually declines over time, the drug might well provide value for money as seen over its entire life cycle, even though its price during patent protection is too high to warrant reimbursement according to the cost-effectiveness decision rule. We show in a theoretical model that welfare could be improved if decision-makers took a longer perspective and initially allowed higher prices than immediate value for money can motivate. We also discuss the real world relevance of applying dynamic cost-effectiveness.
Ependymoblastomatous Exencephaly: A Unique Fetal Malformation
Authors: Mittelbronn Michel , Wolburg Hartwig , Kendziorra Heidemarie , Stopper Ellen , Sousa Patricia , Rorke-Adams Lucy B.
Published: November 2008

Exencephaly/anencephaly is a rare neural tube defect occurring early in embryogenesis. We report a 14-week-old fetus with exencephaly in whom central nervous system tissue was developed and preserved. There were 2 symmetrical structures grossly resembling cerebral hemispheres, which on histologic and ultrastructural study, consisted of a combination of ependymoblastomatous rosettes and canals and primitive neural tissue. The brainstem and spinal cord were partially normally formed, although descending tracts were not apparent. No cerebellar tissue was found. The eyes were formed. This appears to represent a rare example of exencephaly not covered by skin, which did not undergo necrosis and early transformation into a residual area cerebrovasculosa, characteristic of anencephaly. It may be appropriate to regard this as a unique neural tube closure defect that might be termed “ependymoblastomatous exencephaly.”
Gnatho-Thoracopagus Conjoined Twins with near Di-Symmetry: A Case Report of an Unusual form of Conjoined Twinning
Authors: Simon Rchelle A. , Katzman Philip J.
Published: November 2008

The term gnatho-thoracopagus was used previously to describe a remote case of conjoined twins with union involving the mandible. Few reported cases of this type of union exist in the literature. A case of ventrally conjoined twins, with union involving the mandible and near di-symmetry, is presented here and compared with similar previously reported cases. The presented case represents an example of prosopo-thoracopagus, an intermediate between cephalopagus and thoracopagus conjoined twins, although this case does have unique variations.
Umbilical Cord Stricture is Not a Genetic Anomaly: A Study in Twins
Authors: Rodríguez José I. , Mariño-Enríquez Adrián , Suárez-Aguado Judith , Lapunzina Pablo
Published: November 2008

Two recent reports on recurrent cases of umbilical cord stricture (UCS) have opened the debate on the possibility of a genetic basis for this anomaly, traditionally considered to be sporadic. We present a series of 130 cases of UCS located at the fetal insertion, diagnosed among 2067 fetal and infantile autopsies performed during the last 10 years. All cases were macerated stillborn fetuses, and 54.6% were 20 weeks of gestational age. Our study is focused on 2 recurrent episodes and 16 cases occurring in multiple pregnancies. Among twins, males were affected more than females (2.2:1), although no statistical significance was found. Associated umbilical cord anomalies were present in 8 of 16 cases, consisting of hypocoiling (3 cases), hypercoiling (2 cases), excessive length (1 case), vascular tortuosity (1 case), and single umbilical artery (1 case). The most frequent placental finding was obliterative endovasculopathy (6 cases), probably indicating a causal relationship with UCS. Zygosity was analyzed by placental histology and/or a panel of 12 microsatellite markers to classify twins as monozygotic (8 cases) or dizygotic (8 cases). Our data prove that UCS is not a genetic condition because all 8 genetically identical twins were discordant for the anomaly and 2 dizygotic twins with UCS had co-twins also affected. Genetic factors are not implicated in UCS pathophysiology, and parents with a fetal demise due to UCS should be counseled as having a low-recurrence risk for subsequent pregnancies. Because there is not a higher incidence of UCS in multiple gestations, twinning should not be considered a risk factor for UCS.
Androgenetic/Biparental Mosaicism in an Infant with Hepatic Mesenchymal Hamartoma and Placental Mesenchymal Dysplasia
Authors: Reed Robyn C. , Beischel Linda , Schoof Jonathan , Johnson John , Raff Michael L. , Kapur Raj P.
Published: November 2008

Androgenetic/biparental mosaicism, in which a subset of cells has complete paternal uniparental disomy, is associated with placental mesenchymal dysplasia (PMD), which is compatible with fetal development, indicating that fetal organs could also have androgenetic/biparental mosaicism, but few cases of somatic mosaicism have been described. A hepatic mesenchymal hamartoma (HMH) was resected from an otherwise healthy, nondysmorphic, 11-month-old girl, whose prenatal development was complicated by PMD. Placenta, HMH, histologically normal liver, and other tissues were examined for androgenetic/biparental mosaicism by analysis of (1) polymorphic DNA microsatellite markers, (2) the methylation status of an imprinted gene, SNRPN, and (3) immunohistochemically detectable protein products of the imprinted genes p57KIP2 and PHLDA2. The patient's liver, HMH, and 1 placental sample demonstrated an increased ratio of paternal to maternal alleles, indicating androgenetic/biparental mosaicism. The androgenetic component comprised 26% to 60% of the cells. Other tissues, including a 2nd placental sample, white blood cells, umbilical cord, and abdominal fascia, had no detectable androgenetic component. Methylation analysis confirmed a relative excess of the paternally imprinted SNRPN homolog in the normal liver, HMH, and placenta. Placental p57KIP2 immunoreactivity was consistent with androgenetic/biparental mosaicism, but neither p57KIP2 nor PHLDA2 immunohistochemistry were informative for HMH, because neither antigen was detected in control liver samples. We report androgenetic/biparental mosaicism in nonplacental tissues of an infant with PMD and provide the 1st description of genome-wide paternal uniparental disomy in HMH. Androgenetic/biparental mosaicism appears to play a role in the pathogenesis of HMH and other somatic lesions, particularly those associated with PMD.
Comparison of Psychiatric Admissions between City and Country Residents in Western Australia
Authors: Burvill P. W. , Stampfer H. , Reymond J. , Carlson J.
Published: November 2008

Data are presented of all patients with a primary psychiatric diagnosis who were admitted to all psychiatric and non-psychiatric hospitals, in Western Australia during 1976–78. Patients resident in the country were compared with those resident in Perth, the capital city of Western Australia. A high proportion of both Perth and country residents were admitted under non-psychiatrists. Age standardised admission rates were highest for female country residents, the excess rate being mainly due to their very high rates of neurosis/personality disorder. The higher male admission rates for Perth compared with country residents were mainly due to higher Perth rates for alcoholism. The implications of these findings are discussed.
Brief Observations on Research Methods in Clinical Trials
Authors: Lambert Tim
Published: November 2008

This paper will address some of the current issues concerning the conduct of phase III clinical trials. The issues to be discussed fall into two areas – trial design and mensuration of target variable change. The former includes the determination of sample size; selection bias in sample populations due to particular inclusion and exclusion criteria; ensuring trials are randomised, double blind controlled studies; and designing the trial so that the two arms are balanced in every way possible, with especial reference to matching treatment variables. The mensuration of target variable change includes the selection of appropriate rating instruments which are (i) sensitive to target symptoms, (ii) have been adequately profiled psychometrically in a similar population, and (iii) are able to detect change within the time frame of the study. Instruments should be cross-culturally robust if used in multi-country studies and should have validated local versions where possible. Adequate training in the use of the rating instruments should be clearly reported and a clear description of inter-rater reliability assessment and maintenance should be provided. Brief mention will be made of the Cochrane collaboration and the role of evidence-based medicine in clinical trials.
Psychiatric Stigma and the Role of the Psychiatrist
Authors: Walter Garry , Rosen Alan
Published: November 2008

In 1996 the World Psychiatric I-Association (WPA) in conjunction with Lilly Pharmaceuticals announced the launch of a co-ordinated, multidisciplinary approach to counter the stigma of mental illness. In Australia a similar initiative – albeit on a much smaller scale – began six years ago with the establishment of ‘STIGMA’ (‘Stereotypes and Tags Interest Group in the Mental Health Arena’). The STIGMA Group was consulted to determine Australian consumer participation in the WPA initiative. The following paper describes how the STIGMA group emerged out of a preoccupation with public portrayals of psychiatric patients, their families and psychiatric professionals to become a broad group of stakeholders studying psychiatric stigma and possible ways of combating it. To our knowledge, an ongoing group devoted to the study of stigma had no precedent locally or overseas. It is beyond the scope of this paper to describe the origins, phenomenon and painful consequences of stigmatising individuals with mental illness and their families which has been considered in detail elsewhere [1–3].
Network‐based robust fault detection with incomplete measurements
Authors: He Xiao , Wang Zidong , Zhou D. H.
Published: November 2008

In this paper, we deal with the robust fault detection problem for a class of discrete‐time networked systems with unknown inputs. Three types of incomplete measurements frequently occurred in a network environment are simultaneously considered, which include (1) measurements with communication delays, (2) measurements with packet dropouts, and (3) measurements with signal quantization. A unified measurement model utilizing a set of Kronecker delta functions is proposed to describe the delay and missing phenomenon, and the quantization is assumed to be of the logarithmic type. Attention is focused on the analysis and design of a robust full‐order fault detection filter such that, for all admissible unknown inputs and incomplete measurements, the error between residual and fault is kept as small as possible. By augmenting the states of the original system and the fault detection filter, the addressed robust fault detection problem is converted into an auxiliary robustH∞filtering problem. Parameter‐dependent and delay‐probability‐dependent approaches are developed in the design process in order to have a less conservative result. Sufficient conditions for the existence of the desired robust fault detection filters are established in terms of certain linear matrix inequalities (LMIs), and explicit parameters of the desired filter are then characterized if these LMIs are feasible. A numerical example is provided to illustrate the applicability of the proposed technique. Copyright © 2008 John Wiley & Sons, Ltd.
Epidemiology and prognosis of synchronous colorectal cancers
Authors: Latournerie M , Jooste V , Cottet V , Lepage C , Faivre J , Bouvier A-M
Published: November 2008

Background

The aim of this population-based study was to report on the incidence, treatment and prognosis of synchronous colorectal carcinomas.

Methods

Data were obtained from the population-based cancer registry of Burgundy.

Results

Between 1976 and 2004, 15 562 colorectal cancers were diagnosed. Some 3·8 per cent of patients had synchronous colorectal cancers. The risk of having synchronous cancers was higher in men (odds ratio (OR) 1·41 (95 per cent confidence interval (c.i.) 1·19 to 1·68)), when associated adenomas were present (OR 2·02 (95 per cent c.i. 1·69 to 2·41)), when there were adenomatous remnants on pathological examination (OR 2·10 (95 per cent c.i. 1·73 to 2·55)) and in patients aged over 75 years (OR 1·31 (95 per cent c.i. 1·08 to 1·59)). Synchronous tumours were more often located on the same intestinal segment, although the correlation was weak (κ = 0·26). Resection for cure was performed in 74·8 per cent of synchronous cancers and 72·0 per cent of single cancers (P = 0·131). Five-year relative survival for synchronous (48·7 per cent) and single (48·3 per cent) cancers was almost identical. Stage, age, associated adenomas and adenomatous remnants were independent prognostic factors.

Conclusion

Synchronous colorectal cancers convey a similar prognosis to single tumours. Men and patients aged over 65 years with associated adenomas are more prone to multiple colorectal cancers.
Optimal implantation site for pancreatic islet transplantation
Authors: Merani S , Toso C , Emamaullee J , Shapiro A M J
Published: November 2008

Background

Since the first report of successful pancreatic islet transplantation to reverse hyperglycaemia in diabetic rodents, there has been great interest in determining the optimal site for implantation. Although the portal vein remains the most frequently used site clinically, it is not ideal. About half of the islets introduced into the liver die during or shortly after transplantation. Although many patients achieve insulin independence after portal vein infusion of islets, in the long term most resume insulin injections.

Methods

This review considers possible sites and techniques of islet transplantation in small and large animal models, and in humans. Metabolic, immunological and technical aspects are discussed.

Results and conclusion

Many groups have sought an alternative site that might offer improved engraftment and long-term survival, together with reduced procedure-related complications. The spleen, pancreas, kidney capsule, peritoneum and omental pouch have been explored. The advantages and disadvantages of various sites are discussed in order to define the most suitable for clinical use and to direct future research.
Effects of family treatment drug courts on substance abuse and child welfare outcomes
Authors: Worcel Sonia D. , Furrer Carrie J. , Green Beth L. , Burrus Scott W. M. , Finigan Michael W.
Published: November 2008

This paper presents results from the first large‐scale outcome study of American Family Treatment Drug Courts (FTDCs)—specialised courts designed to work with substance‐abusing parents involved with the child welfare system. The paper examines whether court, child welfare and treatment outcomes differed for 301 families served through three FTDCs as compared to a matched sample of 1,220 families with substance abuse issues who received traditional child welfare services. Propensity score weights were used to account for measured differences between the FTDC and comparison groups. Child welfare outcomes were analysed using analytical techniques that controlled for these inherently nested data (i.e. children within a family). Overall, the study found that FTDC mothers had more positive treatment outcomes than similar mothers who were not served by the FTDC. FTDC mothers were more likely to enter substance abuse treatment services than were non‐FTDC mothers, entered treatment more quickly after their initial court petition than did non‐FTDC mothers, spent twice as much time in treatment than did non‐FTDC mothers and were twice as likely to complete at least one treatment episode than non‐FTDC mothers. In addition, data from the study indicate that FTDCs influence a key child welfare variable of interest: FTDC children were significantly more likely to be reunified with their mothers than were unserved children. Copyright © 2008 John Wiley & Sons, Ltd.
Prognostic value of the syntax score in patients undergoing coronary artery bypass grafting for three‐vessel coronary artery disease
Authors: Lemesle Gilles , Bonello Laurent , de Labriolle Axel , Steinberg Daniel H. , Roy Probal , Slottow Tina L. Pinto , Torguson Rebecca , Kaneshige Kimberly , Xue Zhenyi , Suddath William O. , Satler Lowell F. , Kent Kenneth M. , Lindsay Joseph , Pichard Augusto D. , Waksman Ron
Published: November 2008

Background:

The Syntax score prognostic value has recently been highlighted in patients undergoing percutaneous coronary intervention (PCI) for multivessel coronary artery disease (CAD), however its prognostic value in patients undergoing coronary artery bypass grafting (CABG) for multivessel CAD is still unknown. The aim of this study was to evaluate the prognostic value of the Syntax score in patients undergoing CABG for 3‐vessel CAD.

Methods:

A cohort of 320 consecutive patients with multivessel (3‐vessel) CAD who were subjected for CABG were included in this study and divided into tertiles according to the Syntax score (<24.5, 24.5–34, and >34). During the 1‐year follow‐up, cardiovascular events including death, myocardial infarction (MI), and stroke were systematically indexed. The primary end point was the composite criteria death/MI/stroke.

Results:

The Syntax score ranged from 11–74 with a mean of 31.2 ± 12.6 and a median of 28.5 [22–38]. Baseline clinical characteristics were similar among the tertiles. No statistical difference was found for the composite criteria death/MI/stroke: 9.4% versus 7.5% versus 10.4% in the groups with a Syntax score <24.5, 24.5–34, and >34, respectively (P = 0.754).

Conclusion:

Unlike for PCI, the Syntax score has a poor prognostic value for severe cardiovascular events in patients undergoing CABG for 3‐vessel CAD. Other risk scores should be used to predict the outcome of this population. © 2009 Wiley‐Liss, Inc.
ChemInform Abstract: Electronic Structures and Optical Properties of Wurtzite Type LiBSe2 (B: Al, Ga, In): A First‐Principles Study.
Authors: Li Long‐Hua , Li Jun‐Qian , Wu Li‐Ming
Published: November 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Thermal Behavior and Crystal Chemistry of Anhydrous Phosphates. Part 41. Refinement of the Superstructure of FeTi4(PO4)6 — An Example of a Highly Ordered Member of the NASICON Structure Family.
Authors: Schoeneborn M. , Glaum R.
Published: November 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: CaMn1‐xNbxO3 (x ≤ 0.08) Perovskite‐Type Phases as Promising New High‐Temperature n‐Type Thermoelectric Materials.
Authors: Bocher L. , Aguirre M. H. , Logvinovich D. , Shkabko A. , Robert R. , Trottmann M. , Weidenkaff A.
Published: November 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Combined Experimental and Density Functional Theory Studies on the Crystal Structures and Magnetic Properties of Mg(Mg1‐xMnx)2Sb2 (x ≈ 0.25) and BaMn2Sb2.
Authors: Xia Sheng‐Qing , Myers Chad , Bobev Svilen
Published: November 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis and Structure of [C6H14N2] [(UO2)4(HPO4)2 (PO4)2(H2O)]× H2O: An Expanded Open‐Framework Amine‐Bearing Uranyl Phosphate.
Authors: Bray Travis H. , Gorden John D. , Albrecht‐Schmitt Thomas E.
Published: November 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.