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Retinal angiomatous proliferation treated with a combination of intravitreal triamcinolone acetonide and photodynamic therapy with verteporfin.

PURPOSE: Retinal angiomatous proliferation (RAP) is a particularly aggressive form of exudative age-related macular degeneration. Response to laser photocoagulation or to photodynamic therapy (PDT) alone is often disappointing. The purpose of this study was to determine whether intravitreal triamcinolone acetate (TA) injections followed by PDT in eyes with early stage RAP may be effective. METHODS: Prospective uncontrolled study, enrolling 11 patients (11 eyes) with stage 2 RAP, treated with intravitreal TA injection followed by PDT. Patients with large pigment epithelium detachment, RAP stage 3, or pre-existing glaucoma and known steroid responders were excluded. All patients underwent a complete ophthalmic examination including fluorescein and indocyanine green (ICG) angiography and optical coherence tomography (OCT-3) at baseline and at 1, 3, 6, and 12 months. Informed consent was obtained from all patients. RESULTS: Mean follow-up was 14.9 months (range 6 C21 months). Mean age was 82 years. In four patients a small pigment epithelium detachment was found on tomography. Initial visual acuity (VA) ranged from 0.1 to 0.6 on the Snellen scale. After calculating the logarithmic values the authors found an initial mean VA of logMAR 0.61, which improved by 1.5, 0.9, and 0.9 log lines after 3, 6, and 12 months, respectively. Although the VA gain from baseline tended to decrease with time, only 2 patients (18%) had an actual loss of acuity>or=3 lines). Retreatment was required in 5 eyes. CONCLUSIONS: In this prospective pilot study examining the use of intravitreal TA followed by PDT with verteporfin in eyes with stage 2 RAP, without a large pigment epithelium detachment, the authors found a potential benefit in terms of stabilization or even improvement of vision.

Aged↗

Needs survey of Canadian rosacea patients.

BACKGROUND: In 1995, a Rosacea Awareness Program (RAP) was initiated in Canada to make available educational resources for physicians and rosacea patients. Material is in French or English, and is accessible though physician offices and by toll-free telephone. Information was communicated to the public via noncommercial, editorial media. The RAP created a database of rosacea patients in Canada. OBJECTIVE: We investigated if individuals in the database had a confirmed diagnosis of rosacea, how they perceived their treatment by the medical system, and identified their needs. METHODS: A two-page questionnaire was mailed to 7874 individuals registered with the RAP. Thirty percent of these individuals responded. Where comparisons were made a chi-squared statistic was used. RESULTS: Over 70% learned of the RAP via public media. It took patients an average of 5 years to have a diagnosis made after the first symptoms appeared. In the majority of patients (53%) the diagnosis was ultimately made by a specialist. Fifty-eight individuals said they had not discussed their condition with their doctor. Patients were likely to continue on medication that was prescribed (60%) and topical metronidazole was the most common medication used, mostly the gel formulation. Most patients used these twice daily. Patients were very satisfied with treatments and almost 90% had reduced symptoms. Despite receiving explanations and written material, patients expressed a strong interest in more information being available on skin care, make-up, and psychological aspects of rosacea. CONCLUSIONS: The RAP provides a needed educational service and is a useful database. Patients are very knowledgeable about their disease, but despite this and excellent therapeutic responses, the patients demand more information.

Administration, Cutaneous↗

Kinesin-like protein CENP-E is upregulated in rheumatoid synovial fibroblasts.

UNLABELLED: Articular destruction by invading synovial fibroblasts is a typical feature in rheumatoid arthritis (RA),. Recent data support the hypothesis that key players in this scenario are transformed-appearing synovial fibroblasts at the site of invasion into articular cartilage and bone. They maintain their aggressive phenotype toward cartilage, even when first cultured and thereafter coimplanted together with normal human cartilage into severe combined immunodeficient mice for and extended period of time. However, little is known about the upregulation of genes that leads to this aggressive fibroblast phenotype. To inhibit this progressive growth without interfering with pathways of physiological matrix remodelling, identification of pathways that operate specifically in RA synovial fibroblasts is required. In order to achieve this goal, identification of genes showing upregulation restricted to RA synovial fibroblasts is essential. AIMS: To identify specifically expressed genes using RNA arbitrarily primed (RAP)-polymerase chain reaction (PCR) for differential display in patients with RA. METHODS: RNA was extracted from cultured synovial fibroblasts from 10 patients with RA, four patients with osteoarthritis (OA), and one patient with psoriatic arthritis. RAP-PCR was performed using different arbitrary primers for first-strand and second-strand synthesis. First-strand and second-strand synthesis were performed using arbitrary primers: US6 (5'-GTGGTGACAG-3') for first strand, and Nuclear 1+ (5'ACGAAGAAGAG-3'), OPN28 (5'GCACCAGGGGG-3'), Kinase A2+(5'-GGTGCCTTTGG-3') and OPN24 (5'AGGGGCACCA-3') for second strand synthesis. PCR reactions were loaded onto 8 mol/l urea/6% polyacrylamide-sequencing gels and electrophoressed. Gel slices carrying the target fragment were then excised with a razor blade, eluated and reamplified. After verifying their correct size and purity on 4% agarose gels, the reamplified products derived from the single-strand confirmation polymorphism gel were cloned, and five clones per transcript were sequenced. Thereafter, a genbank analysis was performed. Quantitative reverse transcription PCRj of the segments was performed using the PCR MIMIC technique. In-situ expression of centromere kinesin-like protein-E (CENP-E) messenger (m)RNA in RA synovium was assessed using digoxigenin-labelled riboprobes, and CENP-E protein expression in fibroblasts and synovium was performed by immunogold-silver immunohistochemistry and cytochemistry. Functional analysis of CENP-E was done using different approaches (eg glucocorticoid stimulation, serum starvation and growth rate analysis of synovial fibroblasts that expressed CENP-E). RESULTS: In RA, amplification of a distinct PCR product suitable for sequencing could be observed. The indicated complementary DNA fragment of 434 base pairs from RA mRNA corresponded to nucleotides 6615-7048 in the human centromere kinesin-like protein CENP-E mRNA (GenBank accession No. emb/Z15005). The isolated sequence shared greater than 99% nucleic acid (P=2.9e(-169)) identify with the human centromere kinesin-like protein CENP-E. Two base changes at positions 6624 (A to C) and 6739 (A to G) did not result in alteration in the amino acid sequence, and therefore 100% amino acid identity could be confirmed. The amplification of 10 clones of the cloned RAP product revealed the presence of CENP-E mRNA in every fibroblast culture examined, showing from 50% (271.000 +/- 54.000 phosphor imager arbitrary units) up to fivefold (961.000 +/- 145.000 phosphor image arbitrary units) upregulation when compared with OA fibroblasts. Neither therapy with disease-modifying antirheumatic drugs such as methotrexate, gold, resochine or cyclosporine A, nor therapy with oral steroids influenced CENP-E expression in the RA fibroblasts. Of the eight RA fibroblast populations from RA patients who were receiving disease-modifying antirheumatic drugs, five showed CENP-E upregulation; and of the eight fibroblast populations from RA patients receiving steroids, four showed CENP-E upregulation. Numerous synovial cells of the patients with RA showed a positive in situ signal for the isolated CENP-E gene segment confirming CENP-E mRNA production in rheumatoid synovium, whereas in OA synovial tissue CENP-E mRNA could not be detected. In addition, CENP-E expression was independent from medication. This was further confirmed by analysis of the effect of prednisolone on CENP-E expression, which revealed no alteration in CENP-E mRNA after exposure to different (physiological) concentrations of prednisolone. Serum starvation also could not suppress CENP-E mRNA completely. DISCUSSION: Since its introduction in 1992, numerous variants of the differential display method and continuous improvements including RAP-PCR have proved to have both efficiency and reliability in examination of differentially regulated genes. The results of the present study reveal that RAP-PCR is a suitable method to identify differentially expressed genes in rheumatoid synovial fibroblasts. The mRNA, which has been found to be upregulated in rheumatoid synovial fibroblasts, codes for a kinesin-like motor protein named CENP-E, which was first characterized in 1991. It is a member of a family of centromere-associated proteins, of which six (CENP-A to CENP-F) are currently known. CENP-E itself is a kinetochore motor, which accumulates transiently at kinetochores in the G2 phase of the cell cycle before mitosis takes place, appears to modulate chromosome movement and spindle elongation,and is degraded at the end of mitosis. The presence or upregulation of CENP-E has never been associated with RA.The three-dimensional structure of CENP-E includes a coiled-coil domain. This has important functions and shows links to known pathways in RA pathophysiology. Coiled-coil domains can also be found in jun and fos oncogene products, which are frequently upregulated in RA synovial fibroblasts. They are also involved in DNA binding and transactivation processes resembling the situation in AP-1 (Jun/Fos)-dependent DNA-binding in rheumatoid synovium. Most interestingly, these coiled-coil motifs are crucial for the assembly of viral proteins, and the upregulation of CENP-E might reflect the influence of infectious agents in RA synovium. We also performed experiments showing that serum starvation decreased, but did not completely inhibit CENP-E mRNA expression. This shows that CENP-E is related to, but does not completely depend on proliferation of these cells. In addition, we determined the growth rate of CENP-E high and low expressors, showing that it was independent from the amount of CENP-E expression. supporting the statement that upregulation of CENP-E reflects an activated RA fibroblast phenotype. In summary, the results of the present study support the hypothesis that CENP-E, presumably independently from medication, may not only be upregulated, but may also be involved in RA pathophysiology.

Adult↗

Impaired processing of brief, rapidly presented auditory cues in infants with a family history of autoimmune disorder.

Studies have shown that individuals with language disorders, such as developmental dyslexia and specific language impairment, exhibit impairments in the processing of brief, successive, or rapidly changing auditory information. It is also the case that a higher rate of autoimmune disorders have been identified in those with language-based learning disorders and, conversely, that individuals with autoimmune disorders show a higher incidence of language-related disorders. The rapid auditory processing (RAP) deficits described for older individuals with language impairments may also be used as a behavioral marker to identify infants at higher risk for language delays. Thus, we were interested in examining RAP abilities in a subset of infants with a positive family history of autoimmune disorders. Eleven infants from our ongoing prospective longitudinal studies were identified based on parental response to a question about the presence of a family history of autoimmune disease and compared to 11 matched controls. The RAP threshold of each infant was assessed at 6 and 9 months of age using a conditioned head-turn procedure (using tone pairs with brief interstimulus intervals) and an auditory-visual habituation-recognition memory task using computer-generated consonant-vowel syllables (/ba/ vs. /da/). A visual habituation-recognition memory task that did not require processing of brief temporal cues was also administered. Group differences emerged on the infant RAP tasks, and on language outcome measures at 12 and 16 months of age. Infants from families with a history of autoimmune disorder had significantly higher (i.e., poorer) RAP thresholds and lower language scores than did control infants, whereas visual discrimination scores did not differ between family history infants and controls. Moreover, when brief auditory cues were necessary for the discrimination of /ba/ vs. /da/, infants with a family history of autoimmune disorder performed significantly more poorly than did controls. These findings lend support to the hypothesis that a similar mechanism, perhaps a neural-immune interaction, may underlie the observed co-occurrence of autoimmune disorders and learning impairments.

Acoustic Stimulation↗

Increased right or left atrial pressure stimulates release of atrial natriuretic peptides in conscious dogs.

To compare release of immunoreactive atrial natriuretic peptides (iANP) caused by distention of the right and left atria, dogs were prepared with occluding cuffs around either the ascending aorta (n = 5) or the pulmonary artery (n = 4). Graded inflation of the ascending aortic cuff for 60 min caused increments in left atrial pressure (LAP) but no change or a decrease in right atrial pressure (RAP). Plasma iANP increased significantly (P less than 0.01) in response to increases in LAP as small as 2.9 +/- 0.4 mmHg. There was a significant correlation between the increment in LAP and the rise in plasma iANP (r = 0.64, n = 25, P less than 0.01). Graded inflation of the pulmonary artery cuff caused increments in RAP and a fall in LAP. Plasma iANP increased significantly (P less than 0.01) in response to increases in RAP as small as 2.8 +/- 1.1 mmHg. Also, there was a significant correlation between the increments in RAP and the rise in plasma iANP (r = 0.69, n = 20, P less than 0.01). These results indicate that physiologic increases in either RAP or LAP is sufficient to cause increased plasma levels of iANP in conscious dogs.

Animals↗

The molecular response of bone to growth hormone during skeletal unloading: regional differences.

Hind limb elevation of the growing rat provides a good model for the skeletal changes that occur during space flight. In this model the bones of the forelimbs (normally loaded) are used as an internal control for the changes that occur in the unloaded bones of the hind limbs. Previous studies have shown that skeletal unloading of the hind limbs results in a transient reduction of bone formation in the tibia and femur, with no change in the humerus. This fall in bone formation is accompanied by a fall in serum osteocalcin (bone Gla protein, BGP) and bone BGP messenger RNA (mRNA) levels, but a rise in bone insulin-like growth factor-I (IGF-I) protein and mRNA levels and resistance to the skeletal growth-promoting actions of IGF-I. To determine whether skeletal unloading also induced resistance to GH, we evaluated the response of the femur and humerus of sham and hypophysectomized rats, control and hind limb elevated, to GH (two doses), measuring mRNA levels of IGF-I, BGP, rat bone alkaline phosphatase (RAP), and alpha 1(1)-procollagen (coll). Hypophysectomy (HPX) decreased the mRNA levels of IGF-I, BGP, and coll in the femur, but was either less effective or had the opposite effect in the humerus. GH at the higher dose (500 micrograms/day) restored these mRNA levels to or above the sham control values in the femur, but generally had little or no effect on the humerus. RAP mRNA levels were increased by HPX, especially in the femur. The lower dose of GH (50 micrograms/day) inhibited this rise in RAP, whereas the higher dose raised the mRNA levels and resulted in the appearance of additional transcripts not seen in controls. As for the other mRNAs, RAP mRNA in the humerus was less affected by HPX or GH than that in the femur. Hind limb elevation led to an increase in IGF-I, coll, and RAP mRNAs and a reduction in BGP mRNA in the femur and either had no effect or potentiated the response of these mRNAs to GH. We conclude that GH stimulates a number of markers of bone formation by raising their mRNA levels, and that skeletal unloading does not block this response, but the response varies substantially from bone to bone.

Analysis of Variance↗

Cardiohemodynamic effects of nipradilol (K-351) in the dog: comparison with propranolol, nadolol and prazosin.

The cardiohemodynamic effects of nipradilol (K-351) were studied in comparison with those of propranolol, nadolol and prazosin in anesthetized, open-chest dogs. All drugs were administered intravenously. Nipradilol produced dose-dependent decreases in systemic blood pressure (BP), heart rate (HR), venous return (VR) and cardiac output (COP), but virtually no change in right atrial pressure (RAP). Propranolol decreased HR, tended to decrease VR and COP and increased RAP, but produced no change in systemic BP. Nadolol also decreased HR, VR and COP and increased RAP, but did not change systemic BP. Prazosin decreased systemic BP, VR and COP and tended to decrease RAP, but scarcely affected HR. After propranolol or nadolol, nipradilol failed to reduce HR, but still produced definite decreases in systemic BP, VR and COP and a slight decrease in RAP. After prazosin, nipradilol still produced decreases in systemic BP, HR, VR and COP. These results suggest that nipradilol decreases VR and COP mainly by increasing venous capacitance through direct venodilator action and in part by increasing resistance to VR through beta-adrenoceptor blockade. This effect also appears to be responsible for its hypotensive effect.

Adrenergic beta-Antagonists↗

Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence.

STUDY OBJECTIVE: To identify and critically review the published peer-reviewed, English-language studies investigating predictive factors of fluid responsiveness in ICU patients. DESIGN: Studies were collected by doing a search in MEDLINE (from 1966) and scanning the reference lists of the articles. Studies were selected according to the following criteria: volume expansion performed in critically ill patients, patients classified in two groups (responders and nonresponders) according to the effects of volume expansion on stroke volume or on cardiac output, and comparison of responder and nonresponder patients' characteristics before volume expansion. RESULTS: Twelve studies were analyzed in which the parameters tested were as follows: (1) static indicators of cardiac preload (right atrial pressure [RAP], pulmonary artery occlusion pressure [PAOP], right ventricular end-diastolic volume [RVEDV], and left ventricular end-diastolic area [LVEDA]); and (2) dynamic parameters (inspiratory decrease in RAP [Delta RAP], expiratory decrease in arterial systolic pressure [Delta down], respiratory changes in pulse pressure [Delta PP], and respiratory changes in aortic blood velocity [Delta Vpeak]). Before fluid infusion, RAP, PAOP, RVEDV, and LVEDA were not significantly lower in responders than in nonresponders in three of five studies, in seven of nine studies, in four of six studies, and in one of three studies, respectively. When a significant difference was found, no threshold value could discriminate responders and nonresponders. Before fluid infusion, Delta RAP, Delta down, Delta PP, and Delta Vpeak were significantly higher in responders, and a threshold value predicted fluid responsiveness with high positive (77 to 95%) and negative (81 to 100%) predictive values. CONCLUSION: Dynamic parameters should be used preferentially to static parameters to predict fluid responsiveness in ICU patients.

Blood Pressure↗

Echo/Doppler and hemodynamic correlates of vasodilator responsiveness in primary pulmonary hypertension.

To determine correlates of acute vasodilator responsiveness in primary pulmonary hypertension, we retrospectively studied 25 patients, comparing 41 resting echo/Doppler and nine resting catheterization variables with the maximal reduction in pulmonary vascular resistance achieved during vasodilator trials. Twelve vasodilators were tested (mean, 5.6 drugs per patient; range, three to eight). Eight patients were vasodilator responsive, as defined by a reduction in pulmonary vascular resistance greater than or equal to 30 percent in response to at least one agent. Univariate and multivariate analyses revealed only Doppler pulmonic peak flow velocity to be an independent correlate of responsiveness (p less than 0.05). Responders differed from nonresponders in having a higher Doppler pulmonic peak flow velocity (PV) (SD 81 +/- 24 vs 64 +/- 15 cm/s; p = 0.05), lower mean right atrial pressure (RAP) (6 +/- 4 vs 13 +/- 7 mm Hg; p = 0.04), and longer median survival (37 vs 5 months; p = 0.03). Seven of eight responders had RAP less than or equal to 10 mm Hg, and all responders had PV greater than 60 cm/s. Seven of ten patients with both RAP less than or equal to 10 and PV greater than 60 and one of the 15 remaining patients were vasodilator responsive (p less than 0.001). Thus, echo/Doppler and invasive hemodynamic parameters correlate with acute vasodilator responsiveness in primary pulmonary hypertension. Patients with low PV and high RAP values were almost never vasodilator responsive. Doppler pulmonic peak velocity and mean RAP may be useful in identifying patients most likely to respond to acute vasodilator trials and those in whom testing is unlikely to yield positive results.

Adult↗

Selection of screening items for alcohol abuse and alcohol dependence among Mexicans and Mexican Americans in the emergency department.

OBJECTIVE: This article reports on the selection of screening items to detect Mexican or Mexican-American patients in the emergency department (ED) who have alcohol problems and could benefit from an intervention or a referral for treatment. Items are tested against the Rapid Alcohol Problems Screen (RAPS), which has been optimized from standard screening instruments and has outperformed these instruments. METHOD: The performance of individual items from standard screening instruments (CAGE, TWEAK, AUDIT, TRAUMA and BMAST) against International Classification of Diseases, Tenth Revision and Diagnostic and Statistical Manual, Fourth Revision criteria for alcohol abuse and dependence was evaluated in a merged probability sample (N = 869; 72% men) of 537 ED patients from three hospitals in Pachuca, Mexico, and 332 Mexican-American ED patients in Santa Clara County, CA. Logistic regression and tree-classification models were used for item selection. RESULTS: We found a prevalence of 15% for alcohol dependence and a prevalence of 28% for alcohol abuse or dependence in the merged sample. The RAPS items did not perform as well in terms of sensitivity (93%) as the optimal five items identified in these analyses (sensitivity = 98%) for alcohol dependence, but did demonstrate better specificity (79%) than the optimal five items (65%), which is an important consideration in a time of cost containment. Both sets of items showed better sensitivity and positive predictive value but similar Receiver Operating Characteristic values for respondents in the high acculturation group compared to those at other levels of acculturation. Differences in positive predictive value across all subgroups tended to increase at increased cutpoints, especially for the RAPS. CONCLUSIONS: These analyses suggest that the RAPS performs favorably compared to those items optimized, in this sample of Hispanic ED patients. Based on comparative item performance in these analyses, the RAPS may hold promise as a useful tool for screening for alcohol dependence, but requires further evaluation as a stand-alone instrument in comparison with other standard screening instruments.

Adolescent↗

The effects of secretagogues of isolated human gastric glands.

The function of isolated human gastric glands has been studied in vitro by measuring the 14C-aminopyrine accumulation (RAP) in basal, unstimulated, conditions and after stimulation with different secretagogues. A microscale technique was used which enabled determinations of RAP in tissue obtained as gastroscopic biopsies. In addition, oxyntic-gland-containing mucosa was obtained at gastric resections for gastric or prepyloric ulcer disease. Histamine and cAMP derivative both induced maximal stimulation; RAP was approximately three times larger than in basal states. Carbachol induced a smaller but still significant stimulation. Pentagastrin did not increase RAP above the unstimulated level. Combinations of histamine and carbachol or pentagastrin did not induce a larger response than carbachol alone. The peak acid response to pentagastrin or betazole in vivo did not correlate with the maximum RAP in vitro.

1-Methyl-3-isobutylxanthine↗

Specific binding and steroidogenetic effects of atrial natriuretic factor (ANF) in Leydig cells of rats.

Atrial natriuretic factors (ANF) may influence testicular steroidogenesis. This study was conducted to evaluate the presence of specific ANF-binding on isolated adult rat Leydig cells and the effects of ANF on testosterone production. Indirect immunofluorescence technique demonstrates that adult rat Leydig cells possess specific ANF-binding and that rAP-II strongly stimulates the testosterone production. rAP-II exerts its maximal stimulatory effect on the testosterone secretion at low doses (10(-11) M), corresponding at the physiological plasmatic concentration in the adult normal rat. High doses (10(-9)-10(-7) M) of rAP-II show a decline in the stimulatory effect on testosterone secretion. Our data suggest that rAP-II influences the testicular steroidogenesis by a receptorial mechanism; the biphasic effect of rAP-II on the testosterone production may be related to an acute receptorial desensitization phenomena.

Animals↗

Effects of atrial natriuretic factor (ANF) on rat testicular steroidogenesis in vitro.

The aim of this study was to evaluate the effects of rat atrial-peptide type II (rAP-II) on testicular steroidogenesis by isolated adult rat Leydig cells. rAP-II stimulates testosterone secretion. The maximal stimulatory effects of rAP-II on testosterone production occurred at the dose of 10(-11) M. At the same dose this peptide stimulates androstenedione and dehydroepiandrosterone-sulphate production, two important testosterone precursors of delta-4 and delta-5 steroidogenetic pathways, respectively. At higher doses, 10(-9) and 10(-7) M, the stimulatory effect of rAP-II on testosterone secretion is strongly declined, on androstenedione secretion is abolished, whereas on dehydroepiandrosterone-sulphate secretion remains unaffected. These data suggest that rAP-II at low doses exerts a stimulatory effect on the early steroidogenetic step by isolated adult rat Leydig cells. At higher doses this peptide seems to influence the testicular steroidogenesis, probably exerting a limiting reaction step involving the 3-beta-OH-steroid-dehydrogenase activity.

Androstenedione↗

Introducing an innovative method in team conferences.

An innovative method to structure multidisciplinary team conferences in rehabilitation medicine was developed: Rehabilitation Activities Profile report system (RAP-TEAM). Experiences with introduction of RAP-TEAM and the study of its effects on the satisfaction of professionals are described. RAP-TEAM was introduced in three teams. RAP-TEAM did not influence the satisfaction of professionals in two teams; satisfaction in the third team even decreased. Nevertheless, professionals report more benefits than disadvantages of RAP-TEAM. Several possible explanations for these results and the methodological problems with this kind of evaluation study are discussed. The most important explanation is that introduction of an innovative method should be allowed sufficient time before it could become effective. Recommendations for a successful introduction of innovative changes are made. All people concerned must be aware that a process of change is not simple, and needs the full attention of all.

Congresses as Topic↗

Measurement of renal artery pressure in the rat.

The objective of this study was to develop and document a simple technique for the direct measurement of renal artery pressure (RAP) in the rat. RAP was recorded in 13 Sprague-Dawley rats using a glass micropipette fitted to a low displacement pressure transducer. Average mean arterial pressure recorded from a femoral artery catheter was 107.2 +/- 3.2 mmHg compared with a RAP of 103.8 +/- 3.7 mmHg (P less than 0.05). To determine whether the measurement affected renal blood flow (RBF), RBF was determined using radiolabeled microspheres, both before and while recording left RAP. No differences existed between the initial left and right RBFs [7.3 +/- 0.4 %CO/gm (percent cardiac output per gram tissue) vs. 7.3 +/- 0.4 %CO/gm, P greater than 0.9]. The micropipette in the left renal artery did not alter left RBF (control, 7.3 +/- 0.4 %CO/gm vs. experimental, 7.6 +/- 0.4 %CO/gm; P greater than 0.2). Right RBF did not change between successive flow determinations (P greater than 0.5) indicating that a change in renal hemodynamics unrelated to the protocol did not occur. The techniques presented provide an accurate, simple method for the direct measurement of RAP in the rat.

Animals↗

Analysis of bronchovascular downstream blood pressure changes in exercising sheep.

The relative roles of neural and pressure gradient factors, causing a fall or maintenance of bronchial blood flow in exercising sheep, are unknown. These were examined in sheep prepared under thiopentone/isoflurane general anaesthesia with a pulsed Doppler probe mounted on the bronchial artery, and aortic pressure (Pa) catheter in superficial cervical artery. After recovery, Swan-Ganz catheters were inserted under local anaesthesia into the pulmonary artery. Bronchial flow and conductance (Qbr, Cbr), and pressure gradients (Pg; i.e. aortic minus right atrial, Pg_RAP; pulmonary artery, Pg_Ppa; and, left atrial (wedge) Pg_LAP) were derived from continuous records, after switching between downstream sites during and after moderately severe treadmill exercise (3.8 km.h(-1), for 1.7 min, 6 min recovery). The protocol was repeated after combined alpha1,alpha2-adrenoceptor/cholinoceptor blockade using phentolamine methanesulfonate and methscopolamine bromide. Bronchial flow fell in both receptor intact (INT) and (BL) blocked state. Pa rose in INT, but downstream pressures rose only 3.7 (RAP), 2.8 (Ppa) and 2.0 (LAP) mmHg (P for each < 0.05) in both INT and BL. Pg_RAP and Pg_Ppa did not rise, but Pg_LAP rose 4.0 mmHg (P < 0.05). In BL, Pa fell, as did Pg_RAP (7.0 mmHg, P < 0.05), Pg_Ppa (8.9 mmHg, P < 0.001), but Pg_LAP did not change. Thus, downstream pressures change by small amounts, and pressure gradients to RAP and Ppa sites do not change during moderately severe exercise in normal sheep. The fall in Qbr in INT is due to neural factors, but in BL is due to a fall in Pg. The relative rise in Pg_LAP in both INT and BL favours redistribution within total Qbr to the pulmonary capillary/vein/left atrium site.

Animals↗

Rapsynoid/partner of inscuteable controls asymmetric division of larval neuroblasts in Drosophila.

Asymmetric cell division generates daughter cells with different developmental fates. In Drosophila neuroblasts, asymmetric divisions are characterized by (1) a difference in size between the two daughter cells and (2) an asymmetric distribution of cell fate determinants, including Prospero and Numb, between the two daughter cells. In embryonic neuroblasts, the asymmetric localization of cell fate determinants is under the control of the protein Inscuteable (Insc), which is itself localized asymmetrically as an apical crescent. Here, we describe a new Drosophila protein, Rapsynoid (Raps), which interacts in a two-hybrid assay with the signal transduction protein Galpha(i). We show that Raps is localized asymmetrically in dividing larval neuroblasts and colocalizes with Insc. Moreover, in raps mutants, the asymmetric divisions of neuroblasts are altered: (1) Insc is no longer asymmetrically localized in the dividing neuroblast; and (2) the neuroblast division produces two daughter cells of similar sizes. However, the morphologically symmetrical divisions of raps neuroblasts still lead to daughter cells with different fates, as shown by differences in gene expression. Our data show that Raps is a novel protein involved in the control of asymmetric divisions of neuroblasts.

Amino Acid Motifs↗

The relation of daily stressors to somatic and emotional symptoms in children with and without recurrent abdominal pain.

Prior investigations of the relation between stressors and symptoms in children with recurrent abdominal pain (RAP) have focused on major negative life events. This study used consecutive daily telephone interviews to assess daily stressors and symptoms in 154 pediatric patients with RAP and 109 well children. Results showed that patients with RAP reported more frequent daily stressors than well children reported both at home and at school. Idiographic (within-subject) analyses indicated that the association between daily stressors and somatic symptoms was significantly stronger for patients with RAP than for well children. In contrast, the relation between daily stressors and negative affect did not differ between the groups. The relation between daily stressors and somatic symptoms was stronger for patients with RAP who had higher levels of trait negative affectivity.

Abdominal Pain↗