Miracle-dz/UniFAR-FTUs huggingface dataset:
Oleic Acid-Induced Pancreatitis Alters Expression of Transforming Growth Factor-&bgr;1 and Extracellular Matrix Components in Rats

Introduction and Aims Extracellular matrix (ECM) components participate in the process of tissue repair and development of fibrosis in the pancreas. We studied the production kinetics of ECM components and transforming growth factor (TGF)–&bgr;1 and identified their production sites in the pancreas following pancreatitis. Methodology Pancreatitis was induced in rats by a single intraductal infusion of oleic acid. Gene expression of TGF-&bgr;s and ECM components was studied by northern blotting. Pancreatic stellate cell activation was assessed by immunostaining for &agr;-smooth muscle actin (&agr;SMA) and desmin. Results Gene expression of TGF-&bgr;s and ECM components was increased in association with pancreatic fibrosis after 1–2 weeks and remained higher than the control levels for the ensuing 12 weeks. Both &agr;SMA and desmin were strongly immunostained around small vessels and faintly stained in mesenchymal cells and tubular complexes at 1 week. The combination of staining for &agr;SMA plus in situ hybridization for procollagen type III mRNA revealed that procollagen type III mRNA was expressed in both &agr;SMA-positive and &agr;SMA-negative cells in the mesenchyma. Conclusions Our findings demonstrate that expression of genes for both TGF-&bgr;s and ECM components was increased and that both &agr;SMA-positive myofibroblasts and mesenchymal cells are the major sources of ECM components after pancreatitis.
A multidimensional meta-analysis of psychotherapy for PTSD.

OBJECTIVE The authors present a multidimensional meta-analysis of studies published between 1980 and 2003 on psychotherapy for PTSD. METHOD Data on variables not previously meta-analyzed such as inclusion and exclusion criteria and rates, recovery and improvement rates, and follow-up data were examined. RESULTS Results suggest that psychotherapy for PTSD leads to a large initial improvement from baseline. More than half of patients who complete treatment with various forms of cognitive behavior therapy or eye movement desensitization and reprocessing improve. Reporting of metrics other than effect size provides a somewhat more nuanced account of outcome and generalizability. CONCLUSIONS The majority of patients treated with psychotherapy for PTSD in randomized trials recover or improve, rendering these approaches some of the most effective psychosocial treatments devised to date. Several caveats, however, are important in applying these findings to patients treated in the community. Exclusion criteria and failure to address polysymptomatic presentations render generalizability to the population of PTSD patients indeterminate. The majority of patients posttreatment continue to have substantial residual symptoms, and follow-up data beyond very brief intervals have been largely absent. Future research intended to generalize to patients in practice should avoid exclusion criteria other than those a sensible clinician would impose in practice (e.g., schizophrenia), should avoid wait-list and other relatively inert control conditions, and should follow patients through at least 2 years.
Psychotherapeutic Benefits of Opioid Agonist Therapy

ABSTRACT Opioids have been used for centuries to treat a variety of psychiatric conditions with much success. The so-called “opium cure” lost popularity in the early 1950s with the development of non-addictive tricyclic antidepressants and monoamine oxidase inhibitors. Nonetheless, recent literature supports the potent role of methadone, buprenorphine, tramadol, morphine, and other opioids as effective, durable, and rapid therapeutic agents for anxiety and depression. This article reviews the medical literature on the treatment of psychiatric disorders with opioids (notably, methadone and buprenorphine) in both the non-opioid-dependent population and in the opioid-dependent methadone maintenance population. The most recent neurotransmitter theories on the origin of depression and anxiety will be reviewed, including current information on the role of serotonin, N-Methyl d-Aspartate, glutamate, cortisol, catecholamine, and dopamine in psychiatric disorders. The observation that methadone maintenance patients with co-existing psychiatric morbidity (so called dual diagnosis patients) require substantially higher methadone dosages by between 20% and 50% will be explored and qualified. The role of methadone and other opioids as beneficial psychiatric medications that are independent of their drug abuse mitigating properties will be discussed. The mechanisms by which methadone and other opioids can favorably modulate the neurotransmitter systems controlling mood will also be discussed.
Attitudes of patients and physicians to insulin therapy in Japan: an analysis of the Global Attitude of Patients and Physicians in Insulin Therapy study

ABSTRACT Background: The barriers to insulin therapy perceived by Japanese patients with diabetes and their physicians are unclear. Research design and methods: We performed sub-analyses of the Global Attitude of Patients and Physicians in Insulin Therapy (GAPP™) study, which included 100 Japanese physicians (of 1250 participating physicians) and 150 Japanese patients (of 1530 patients) who participated in Internet surveys (physicians) or computer-assisted telephone surveys (patients) across eight countries in 2010. We compared the results of Japanese participants with those obtained for the other seven countries. Results: Overall, 44% of the Japanese patients reported omission or non-adherence to insulin, a greater value than that reported in other countries. Japanese physicians reported that non-adherence to insulin was driven by their patients’ lifestyles. A greater proportion of patients had a history of hypoglycemia in Japan than in other countries. Most of the physicians (94%) and patients (84%) in Japan reported that the currently available insulin treatment regimens do not fit the diverse lifestyles of patients. Conclusions: Many Japanese patients receiving insulin therapy omit or do not adhere to insulin, possibly because of fear of hypoglycemia, or for lifestyle reasons. Insulin regimens that reduce the risk of hypoglycemia without interfering with patients’ lifestyles are needed.
Distinct Phenotypes among Plasma Membrane Ca2+‐ATPase Knockout Mice

Abstract: Ca2+ gradients across the plasma membrane, required for Ca2+ homeostasis and signaling, are maintained in part by plasma membrane Ca2+‐ATPase (PMCA) isoforms 1–4. Gene targeting has been used to analyze the functions of PMCA1, PMCA2, and PMCA4 in mice. PMCA1 null mutant embryos die during the preimplantation stage, and loss of a single copy of the PMCA1 gene contributes to apoptosis in vascular smooth muscle. PMCA2 deficiency in sensory hair cells of the inner ear causes deafness and balance defects, most likely by affecting both intracellular Ca2+ and extracellular Ca2+ in the endolymph. PMCA2 is required for viability of certain neurons, consistent with a major role in maintenance of intracellular Ca2+. Surprisingly, loss of PMCA2 in lactating mammary glands causes a sharp reduction in milk Ca2+, consistent with a macrocalcium secretory function. Although PMCA4 is widely expressed and is the most abundant isoform in some tissues, null mutants appear healthy. However, male PMCA4 null mutants are infertile due to a failure of hyperactivated sperm motility resulting from the absence of PMCA4 in the sperm tail, and Ca2+ signaling in B lymphocytes, involving interactions between PMCA4, CD22, and the tyrosine phosphatase SHP‐1, is defective. Studies of bladder smooth muscle from PMCA4 null mutants and PMCA1 heterozygous mice suggest that PMCA1 and PMCA4 play different roles in smooth muscle contractility, with PMCA1 contributing to overall Ca2+ clearance and PMCA4 being required for carbachol‐stimulated contraction. These phenotypes indicate that PMCA1 serves essential housekeeping functions, whereas PMCA4 and particularly PMCA2 serve more specialized physiological functions.
In vivo evidence of an endothelin-induced vasopressor tone after inhibition of nitric oxide synthesis in rats.

BACKGROUND Continuous production of nitric oxide (NO) from endothelial cells permanently inhibits the synthesis and the vasoconstrictor effects of endothelin. Thus, inhibition of NO synthesis might unmask a vasopressor response to endothelin. To assess whether endothelin contributes to the pressor response induced by inhibition of NO synthesis, we tested whether bosentan, a nonpeptide antagonist of ETA and ETB endothelin receptors, affected the hypertensive response induced by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). METHODS AND RESULTS Anesthetized rats received increasing doses of L-NAME (0.1 to 3 mg.kg-1) in the absence or the presence of bosentan (3 mg.kg-1 IV 15 minutes before L-NAME). Bosentan itself did not affect blood pressure. L-NAME induced a dose-dependent increase in mean arterial pressure (percent increase from baseline after 3 mg.kg-1, 25 +/- 5%), and this was reduced by bosentan (13 +/- 3%; P < .05) or by the selective ETA antagonist BQ-123 (3 mg.kg-1: controls, 25 +/- 4%; BQ-123, 14 +/- 5%; P < .01). In contrast, bosentan did not affect the pressor response to phenylephrine (1 to 100 micrograms.kg-1). The response to L-NAME (3 mg.kg-1) was also reduced by bosentan in ganglion-blocked (chlorisondamine 2.5 mg.kg-1: controls, 89 +/- 10%; bosentan, 45 +/- 7%) or pithed rats (controls, 165 +/- 9%; bosentan, 85 +/- 12%; P < .01). Bosentan also inhibited the pressor response to another inhibitor of NO synthesis, NG-nitro L-arginine (3 mg.kg-1) in normal (controls, 24 +/- 5%; bosentan, 10 +/- 3%; P < .01) or ganglion-blocked (controls, 86 +/- 13%; bosentan, 25 +/- 8%; P < .01) rats. Finally, L-NAME induced a modest increase in plasma levels of endothelin-1 (controls, 26.8 +/- 4.1 pg.mL-1; L-NAME, 38.5 +/- 3.3 pg.mL-1; P < .05). CONCLUSIONS These experiments demonstrate that inhibition of NO synthesis unmasks a tonic pressor influence of endothelin, suggesting that this peptide could play a major role in pathophysiological situations associated with an impaired formation of NO.
Dose effect of imatinib (IM) in patients (pts) with metastatic GIST - Phase III Sarcoma Group Study S0033.

9005 Background: Although IM induces high rates of objective responses and durable disease control in patients (pts) with metastatic GIST, the potential impact of dose on clinical outcomes remains uncertain.At ASCO 2003, this trial reported no differences in progression-free or overall survival between two initial dose levels of IM. The outcomes of pts who crossed over to the higher dose arm are now reported. METHODS Phase III trial in pts with metastatic GIST randomized to one of two dose levels (400 mg vs. 800 mg) of IM daily. The primary aim was to assess the impact of Imatinib dose on overall survival. Pts whose disease progressed on the lower dose were considered to cross over to receive the higher dose IM therapy. RESULTS As of December 9, 2003, 320 of the initial 746 pts (43%) remain on study. Median follow-up among the 527 surviving pts is now 768 days (range 70-1029); median overall survival has still not been reached for either arm of the trial. Survival estimates at 2 years are 78% (95% confidence interval 73-82%) for the IM 400 arm vs. 73% (95% CI 68-77%) for the IM 800 arm. Progression-free survival at 2 years is estimated at 50% (95% CI 45-55%) vs. 53% (95% CI 47%-58%) (p>0.05) for the 400 vs. 800 mg arms, respectively. 164 pts with initial dose of 400/d have had progression of disease; 88/164 pts with progression at the lower dose have crossed over to the 800/d IM therapy. Median follow-up on crossover therapy is 307 days (range 1-852 d). Following crossover, 5 of 68 evaluable pts (7%) have demonstrated PR and an additional 20 pts (29%) have achieved stable disease. Median progression-free survival and overall survival following crossover are 4 months and 19 months, respectively. CONCLUSIONS This multicenter study continues to demonstrate no significant differences between these two dose levels of IM while supporting the durable survival benefits of this agent in pts with metastatic GIST. The clinical benefit of dose escalation to 800 mg after progression on 400 is unclear, although a subset of pts have had objective benefit with continued IM dosing. Future studies should define the optimal management of GIST pts following limited progression on IM therapy. [Table: see text].
Effects of FK506 on nerve regeneration and reinnervation after graft or tube repair of long nerve gaps

We compared the effects of FK506 administration on regeneration and reinnervation after sciatic nerve resection and repair with an autologous graft or with a silicone tube leaving a 6‐mm gap in the mouse. Functional reinnervation was assessed by noninvasive methods to determine recovery of motor, sensory, and sweating functions in the hindpaw over 4 months after operation. Morphometric analysis of the regenerated nerves was performed at the end of follow‐up. The nerve graft allowed for faster and higher levels of reinnervation in the four functions tested than silicone tube repair. Treatment with FK506 (for the first 9 weeks only) resulted in a slight, although not significant, improvement of the onset of reinnervation and of the maximal degree of recovery achieved after autografting. The recovery of pain sensibility and of the compound nerve action potentials in the digital nerves, which directly depend on axonal regeneration, showed better progression with FK506 than reinnervation of muscles and sweat glands, which require reestablishment of synaptic contacts with target cells. The myelinated fibers in the regenerated nerve showed a more mature appearance in the FK506‐treated rats. However, FK506 showed a marginal effect in situations in which regeneration was limited, as in a silicone tube bridging a 6‐mm gap in the mouse sciatic nerve. In conclusion, treatment with FK506 improved the rate of functional recovery after nerve resection and autograft repair. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 905–915, 2001
THE ANALYSIS OF REACTION NORMS FOR AGE AND SIZE AT MATURITY USING MATURATION RATE MODELS

Abstract Reaction norms for age and size at maturity are being analyzed to answer important questions about the evolution of life histories. A new statistical method is developed in the framework of time-to-event data analysis, which circumvents shortcomings in currently available approaches. The method emphasizes the estimation of age-and size-dependent maturation rates. Individual probabilities of maturation during any given time interval follow by integrating maturation rate along the growth curve. The integration may be performed in different ways, over ages or sizes or both, corresponding to different assumptions on how individuals store the operational history of the maturation process. Data analysis amounts to fitting generalized nonlinear regression models to a maturation status variable. This technique has three main advantages over existing methods: (1) treating maturation as a stochastic process enables one to specify a rate of maturation; (2) age and size at which maturation occurs do not have to be observed exactly, and bias arising from approximations and interpolations is avoided; (3) ages at which sizes are measured and maturation status are observed can differ between individuals. An application to data on the springtail Folsomia candida is presented. Models with age-dependent integration of maturation rates were preferred. The analysis demonstrates a significant size dependence of the maturation rate but no age dependence.
The Effect of the Z-Track Technique on Pain and Drug Leakage in Intramuscular Injections

Purpose/Aims: The aim of this study was to investigate the effects of the Z-track technique in the administration of intramuscular diclofenac, a nonsteroidal anti-inflammatory drug, on pain and drug leakage. Design: This is a semiexperimental and randomized controlled study. Methods: It was felt necessary to conduct this study to compare the effects on pain and drug leakage of the standard intramuscular injection method and the “Z-track technique,” which is claimed to be helpful in this regard. The study was conducted in a government hospital in the Marmara region of Turkey. The research sample consisted of 60 patients, 26 female and 34 male, whose ages varied from 18 to 65 years. Sixty patients were randomly divided into 2 equal groups—the experimental group and the control group. The Z-track technique was used for intramuscular injection with the experimental group, whereas, with the control group, the standard technique of intramuscular injection was used. The patients of both groups were injected with 3-mL diclofenac sodium as prescribed by their doctor. Immediately after the procedure was finished and the needle was withdrawn, a different researcher used a 7 × 7-cm pre-prepared and sterilized standard drying paper to press on the needle entry point. The diameter of leakage was measured with a millimetric ruler and recorded on a data collection form. During this procedure, another nurse who was blind to the injection technique assessed the pain felt during the injection by means of the Visual Analog Scale. Results: In the experimental group, mean pain severity was found to be 28.30 ± 23.0, and mean drug leakage was 6.93 ± 4.62 mm, whereas, in the control group, these values were 36.40 ± 28.40 and 10.03 ± 3.69 mm, respectively. Conclusions: Drug leakage was reduced when administering intramuscular diclofenac sodium by the Z technique, but pain severity was not significantly reduced.
Unilateral ureteral obstruction in neonatal rats leads to renal insufficiency in adulthood.

BACKGROUND Although unilateral ureteropelvic junction obstruction is the most common cause of congenital obstructive nephropathy in infants and children, management remains controversial, and follow-up after pyeloplasty is generally limited to the pediatric ages. We have developed a model of temporary unilateral ureteral obstruction (UUO) in the neonatal rat: One month following the relief of five-day UUO, the glomerular filtration rate (GFR) of the postobstructed kidney was normal despite a 40% reduction in the number of glomeruli and residual vascular, glomerular, tubular, and interstitial injury. METHODS To determine whether hyperfiltration and residual injury of remaining nephrons leads to progression of renal insufficiency in later life, 31 rats were sham operated or subjected to left UUO at one day of age, with relief of UUO five days later, and were studied at one year of age. GFR was measured by inulin clearance, and the number of glomeruli, tubular atrophy, glomerular sclerosis, and interstitial fibrosis were measured by histomorphometry in sham, obstructed (UUO), and intact opposite kidneys. Intrarenal macrophages and alpha-smooth muscle actin were identified by immunohistochemistry. RESULTS Despite relief of UUO, ultimate growth of the postobstructed kidney was impaired. The number of glomeruli was reduced by 40%, and GFR was decreased by 80%. However, despite significant compensatory growth of the opposite kidney, there was no compensatory increase in GFR, and proteinuria was increased. Moreover, glomerular sclerosis, tubular atrophy, macrophage infiltration, and interstitial fibrosis were significantly increased not only in the postobstructed kidney, but also in the opposite kidney. CONCLUSIONS Although GFR is initially maintained following relief of five-day UUO in the neonatal rat, there is eventual profound loss of function of the postobstructed and opposite kidneys because of progressive tubulointerstitial and glomerular damage. These findings suggest that despite normal postoperative GFR in infancy, children undergoing pyeloplasty for ureteropelvic junction obstruction should be followed into adulthood. Elucidation of the cellular response to temporary UUO may lead to improved methods to assess renal growth, injury, and functional reserve in patients with congenital obstructive nephropathy.
Contrast-enhanced ultrasound Doppler examination of the retrobulbar arteries.

PURPOSE To evaluate the diagnostic usefulness of an ultrasound contrast agent in examination of the retrobulbar arteries. MATERIAL AND METHODS Ten healthy volunteers received a galactose-based echo-contrast medium (Levovist) by i.v. infusion. The ophthalmic, central retinal, the nasal and the temporal posterior ciliary arteries and the short ciliary arteries were studied in 19 eyes by color and spectral Doppler ultrasonography before and after contrast administration. Peak systolic and end diastolic velocities and spectral Doppler indices (pulsatility and resistive) were assessed. The quality of the spectral and color Doppler imaging of the arteries were visually graded on a 5-point scale. RESULTS There were significant differences in pre- and post-contrast peak systolic velocities in the ophthalmic arteries (p<0.05), but not in the other retrobulbar arteries, or in any of the spectral Doppler indices. After contrast administration the mean spectral Doppler score for vessels poorly visualized before contrast increased from 2.2 (+/-0.4) to 3.1 (+/-0.9). The number of short ciliary arteries with sufficient spectral Doppler quality increased from 7 prior to contrast to 14 following contrast. Prior to the infusion of Levovist, 62 (73%) out of 85 retrobulbar arteries could be evaluated with a sufficient spectral Doppler quality. Following the administration of contrast 66 (78%) arteries had sufficient spectral Doppler quality. However, by combining the results of the pre- and post-contrast examinations, sufficient spectral Doppler quality was obtained in 77 (91%) of the 85 retrobulbar arteries. CONCLUSION Contrast enhancement increased the number of detectable retrobulbar vessels. However, in the case of good quality pre-contrast imaging of the retrobulbar vessels, the use of Levovist did not add any substantial diagnostic information. The optimal spectral Doppler results were obtained when both pre- and post-contrast examinations were performed.
Clinical outcomes in breast angiosarcoma patients: A rare tumor with unique challenges

Breast angiosarcoma (AS) accounts for less than 1% of all breast cancers. The goal of this study was to determine patient outcomes in radiation‐associated angiosarcoma of the breast (RAAS) and sporadic AS. We evaluated patterns of recurrence and predictors of breast AS survival.