tbuckley/cabot-search huggingface dataset:
Motor neuropathy in porphobilinogen deaminase–deficient mice imitates the peripheral neuropathy of human acute porphyria
Authors: Raija L.P. Lindberg, Rudolf Martini, Matthias Baumgartner, Beat Erne, Jacques Borg, Jürgen Zielasek, Kenneth Ricker, Andreas Steck, Klaus V. Toyka, Urs A. Meyer
Journal: Journal of Clinical Investigation (1999)

Acute porphyrias are inherited disorders caused by partial deficiency of specific heme biosynthesis enzymes. Clinically, porphyrias are manifested by a neuropsychiatric syndrome that includes peripheral neuropathy. Although much is known about the porphyrias’ enzyme defects and their biochemical consequences, the cause of the neurological manifestations remains unresolved. We have studied porphyric neuropathy in mice with a partial deficiency of porphobilinogen deaminase (PBGD). PBGD-deficient mice (PBGD–/–) imitate acute porphyria through massive induction of hepatic δ-aminolevulinic acid synthase by drugs such as phenobarbital. Here we show that PBGD–/– mice develop impairment of motor coordination and muscle weakness. Histologically femoral nerves of PBGD–/– mice exhibit a marked decrease in large-caliber (>8 μm) axons and ultrastructural changes consistent with primary motor axon degeneration, secondary Schwann cell reactions, and axonal regeneration. These findings resemble those found in studies of affected nerves of patients with acute porphyria and thus provide strong evidence that PBGD deficiency causes degeneration of motor axons without signs of primary demyelination, thereby resolving a long-standing controversy. Interestingly, the neuropathy in PBGD–/– mice developed chronically and progressively and in the presence of normal or only slightly (twofold) increased plasma and urinary levels of the putative neurotoxic heme precursor δ-aminolevulinic acid. These data suggest that heme deficiency and consequent dysfunction of hemeproteins can cause porphyric neuropathy.
Oxidative DNA damage triggers ProNGF-Mediated apoptosis in the striatum of 6-OHDA-treated rats
Authors: Tao Wang, Pingping Zuo, Piu Chan
Journal: Molecular Neurodegeneration (2012)

Background Oxidative DNA damage generated by 6-hydroxydopamine (6-OHDA) may initiate a programmed cell death cascade called apoptosis and plays an important role in the pathogenesis of Parkinson’s disease (PD). ProNGF, a precursor of nerve growth factor (NGF), is found to be involved in neuronal apoptosis of neurodegenerative diseases such as PD. Therefore, we have tested the presumption that proNGF-mediated apoptosis might be initiated by oxidative DNA damage in 6-OHDA treated rats.
Cytomegalovirus Retinitis Treatment
Authors: William G. Powderly
Journal: JAMA (1997)

<h3>Background:</h3> Sustained-release, intraocular implants that deliverganciclovir are an alternative method for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency sydrome (AIDS). <h3>Methods:</h3> We conducted a randomized study of 188 patients with AIDS and newly diagnosed cytomegalovirus retinitis. The patients were randomly assigned to treatment with an implant delivering 1μg of ganciclovir per hour, an implant delivering 2μg of ganciclovir per hour, or intravenous ganciclovir. The primary outcome we studied was propression of cytomegalovirus retinitis. <h3>Results:</h3> The median time to propression of retinitis was 221 days with the 1-μg-per-hour implant (75 eyes), 191 days with ganciclovir administered intravenously (76 eyes; P&lt;0.001). The risk of progression of retinitis was almost three times as great among patients treated with intrave-nous ganciclovir as among those treated with a ganciclovir implant (risk ratio, 2.8; P&lt;0.001). However, the risk of disease in the initially uninvolved eye was lower with intravenous ganciclovir than with a ganciclovir implant (risk ratio, 0.5; P=0.19). Patients treated with intravenous ganciclovir were also less likely to the have extraocular cytomegalovirus infection (0, vs. 10.3 percentin the two implant groups; P=0.04). <h3>Conclusions:</h3> For the treatment of cytomegalovirus retinitis, thesustained releasse ganciclovir implant is more effective than intravenous ganciclovir, but patients treated with a ganciclovir implant alone remain at greater risk for the development of cytomegalovirus disease outside of the treated eye.
Flow Volume and Shunt Quantification in Pediatric Congenital Heart Disease by Real-Time Magnetic Resonance Velocity Mapping
Authors: Hermann Körperich, Jürgen Gieseke, Peter Barth, Romhild Hoogeveen, Hermann Esdorn, Andreas Peterschröder, Hans Meyer, Philipp Beerbaum
Journal: Circulation (2004)

Flow quantification in real time by phase-contrast MRI (PC-MRI) may provide unique hemodynamic information in congenital heart disease, but available techniques have important limitations. We sought to validate a novel real-time magnetic resonance flow sequence in children.In 14 pediatric patients (mean age 5.2+/-2.0 years) with cardiac left-to-right shunt, pulmonary (Q(p)) and aortic (Q(s)) flow rates were determined by nontriggered free-breathing real-time PC-MRI with single-shot echo-planar imaging combined with sensitivity encoding, which yielded 25 phase images per second at 2.7x2.7-mm in-plane resolution (field of view 30x34 cm2). Over a 9.5-second period that included 2 to 5 respiratory cycles, 16.6+/-2.6 subsequent stroke volumes (range 13 to 22) were acquired in each vessel. Results were compared with conventional retrospectively ECG-gated PC-MRI. Mean Q(p)/Q(s) by conventional PC-MRI was 1.91+/-0.64, and it was 1.94+/-0.68 (mean+/-SD) by real-time PC-MRI. For blood flow rate through pulmonary artery and aorta, we found differences of 2% to 3% (Bland-Altman analysis), with lower limits of agreement of -11% to -13% (mean-2 SD) and upper limits of 18% to 19% (mean+2 SD), which demonstrated good agreement between both methods. Mean difference for Q(p)/Q(s) was 1%, with limits of agreement ranging between -18% and 22% (mean+/-2 SD). High repeatability but some flow overestimation was observed in vitro (pulsatile flow phantom) with real-time PC-MRI, whereas conventional PC-MRI was accurate. Beat-to-beat stroke-volume variation was 6.1+/-2.3% in vivo and 3.7+/-0.3% in vitro.Beat-to-beat quantification of pulmonary and aortic flows and hence left-to-right shunt within a few seconds is reliable by nontriggered real-time PC-MRI with echo-planar imaging and sensitivity encoding. Good spatial/temporal resolution and a large field of view may render the sequence valuable for multiple applications in congenital heart disease.
Analysis of the effects of food and of digestive secretions on the small intestine of the rat: III. Mucosal mass, activity of brush border enzymes, and in vivo absorption of galactose, sodium, and potassium
Authors: R. Ecknauer, G. Feyerabend, H. Raffler
Journal: Gut (1978)

A modified Roux-en-y repositioning of rat proximal small intestine resulted in a gut segment (A) exposed only to digestive secretions, but not to food and a gut segment (B) exposed to food, stomach juice and by reflux only to digestive secretions, and a third segment (C) exposed to both, food and digestive secretions. The changes in segment A were qualitatively very similar to those occurring after removal of luminal nutrition (intravenous feeding, self-emptying blind loop, and Thiry Vella loop). These findings support the hypothesis that the presence of luminal nutrition is a major factor regulating mucosal mass and enzyme activity in rat proximal small intestine. The changes in the luminal environment in segment B caused an increase in mucosal mass (in the proximal half only), an increase in sucrase activity which paralleled the increase in mucosal mass, and no change in activity of alkaline phosphatase which in fact was a decrease in activity `at the cellular level9. Later on the net absorption of sodium and potassium was improved and the disappearance of galactose was unchanged when referred to unit length of small intestine. In segment C there was a small increase in mucosal mass, an increase in activity only for alkaline phosphatase, and an improvement of the net absorption of sodium without changes in the disappearance of galactose. These changes were compatible with a more proximal promotion of a distal gut segment.
Descent of Testis in Relation to Temperature
Authors: A. W. Badenoch
Journal: BMJ (1945)

Infected cases Healed 6 5 32 ,, 21 Unhealed .. 6 Penicillin Series Control Series All Cases Combined Site of Amputation or No. Average Time No. Average Time No. Average Time Re-amputation of Operation to of Operation to of Operation to Cases Limb-fitting Cases Limb-fitting Cases Limb-fitting Above elbow 2 101 wecks 6 9 weeks 8 91 weeks Belowelbow.. 2 11 ,, 10 51 ,, 12 6, Above knee .. 19 9 ,, 11 71 ,, 30 8 , Below knee .. 11 12 ,, 29 12 ,, 40 12and those not receiving post-operative penicillin.The results are given for the various amputation sites.It should be noted that the most difficult site to obtain a good result is below the knee, all but 2 of the 12 cases of delayed healing being below- knee amputations.Conclusions The best indications of the success of an amputation or re- amputation are: first, the shortness of time between operation and readiness of the stump for limb-fitting; secondly, the sub- sequent behaviour of the stump under the strain of wearing an artificial limb.Time alone can show the latter, but the former can be worked out quite easily and gives a reasonable index of the degree of success.It may be added that a rapidly healing stump is usually sounder than a slowly healing one.Broadly speaking, these series give us the results in 3 types of case.First, potentially or actually infected cases receiving post-operative penicillin ; secondly, uninfected cases not receiving penicillin ; and, thirdly, potentially or actually infected cases not receiving post-operative penicillin.It is evident that in the uninfected cases the results were best, but they were only slightly better than in the infected cases receiving post-operative penicillin ; the relevant average times of healing were 7 and 10 weeks respectively.It should be remembered that many of these infected cases had been grossly infected, and could not have undergone re-amputation for weeks or months later had it not been possible to administer post-operative penicillin ; yet there were no failures in this series and only 3 cases of delayed healing.In the third series, even with 8 failures not included, it is found that the average healing-time was 21 weeks-more than twice the period in similar cases which had received penicillin after operation.From these results it can be claimed that the use of penicillin not only shortens the time between operation and limb-fitting.but makes it poss.bleto operate on doubtful cases considerably earlier than would otherwise be feasible.Convalescence is shortened and a far better prospect of success is assured.Summary A report is given of 102 amputations and re-amputations.Of these 55 were infected or potentially so at the time of operation; 34 of them received post-operative penicillin and 21 did not.The results show that, in selected cases; it is possible to operate on infected cases much earlier with than without penicillin, and with
A skeptical position on “musical emotions” and an alternative proposal
Authors: Vladimir J. Konečni
Journal: Behavioral and Brain Sciences (2008)

Abstract Key premises of the target article by Juslin &amp; Västfjäll (J&amp;V) are challenged. It is also shown that most of the six “psychological mechanisms” proposed by the authors as underlying the induction of emotion by music involve nonmusical proximal causes. As a replacement for “musical emotions,” the state of being-moved – from the recently developed Aesthetic Trinity Theory – is proposed.
The importance of epithelial uptake systems in lung toxicity.
Authors: L L Smith, C P Lewis, I Wyatt, G M Cohen
Journal: Environmental Health Perspectives (1990)

The discovery that the herbicide paraquat was selectively accumulated by the lung, both in vivo and in vitro, in comparison with other tissues, provided an explanation for its selective toxicity to the lung. This uptake process is energy dependent and obeys saturation kinetics. A characterization of the process led to the identification of endogenous chemicals that are the natural substrates for the system. Among these are a series of diamines and polyamines, as well as the diaminodisulfide cystamine. It appears that paraquat, because of specific structural similarities to these endogenous polyamines, is mistakenly accumulated by the lung. This uptake process is specifically located in the alveolar Type II cell, the Clara cell, and probably the alveolar Type I cell. With the development of knowledge of the structural requirements of chemicals to be accumulated by this system, it is possible to predict which chemicals will be accumulated by the lung or design molecules that are targeted to the alveolar epithelial and Clara cells. In the wider perspective, this polyamine uptake system has been found on a number of cancerous cells or tissues. With the knowledge of the uptake system in the lung, it should be possible to design drugs that will be specifically concentrated in cells that possess this system.
Chronic ACE inhibition by quinapril modulates central vasopressinergic system
Authors: Frank Muders, Dietmar Elsner, Karin Jandeleit, Udo Bahner, Eckhard P. Kromer, Ingrid Kirst, Günter A.J. Riegger, Miklos Palkovits
Journal: Cardiovascular Research (1997)

Objective: The role of the brain as a target for angiotensin converting enzyme (ACE) inhibitors in the treatment of heart failure and hypertension is unclear. To test the hypothesis that ACE inhibitors may modulate other central neuropeptide systems such as the central vasopressin system, we studied the effects of chronic treatment with the ACE inhibitor, quinapril, on ACE activity and on central vasopressin content in specific brain areas in rats. Methods: 22 rats were chronically treated with quinapril (6 mg·kg−1 BW per gavage daily for 6 weeks; untreated controls, n=14). ACE density in various brain regions was assessed by in vitro autoradiography using the specific ACE inhibitor, 125I-351A. Vasopressin content was determined in 19 brain areas (micropunch technique) known to be involved in cardiovascular regulation. Results: Following chronic quinapril treatment ACE was significantly decreased in the thalamus (−38%), hypothalamus (−37%), hypophysis (−35%), cerebellum (−36%), choroid plexus (−20%), and locus coeruleus (−35%). Additionally, a marked reduction in serum ACE activity (−97%) was observed. Plasma levels of vasopressin were significantly decreased after quinapril treatment (0.97[s.e.m. 0.11] vs. 1.63[0.24] pg·ml−1 in controls, P<0.05). Vasopressin content was significantly reduced in 9 of 19 specific brain areas. Regarding the hypothalamic vasopressin-producing nuclei, vasopressin was decreased in the paraventricular (292[197] vs. 2379[585] pg·mg−1 crotein in controls; P<0.001) and supraoptic nuclei (13618[1979] vs. 24525[3894] pg·mg−1 protein; P<0.05), but not in the suprachiasmatic nucleus. Vasopressin content was significantly reduced in brain areas connected by vasopressinergic fibres originating in the hypothalamic paraventricular nucleus: namely central gray, subcommissural organ, organum vasculosum laminae terminalis, dorsal raphe nucleus, and locus coeruleus. Vasopressin content was also significantly reduced in the median eminence (5887[1834] vs. 28321[4969] pg·mg−1 protein, P<0.001), where the hormone is mainly concentrated in the hypothalamo-hypophysial tract. Conclusions: Autoradiographic studies in vitro indicate that orally administered quinapril suppresses central ACE activity after chronic treatment. ACE inhibition by quinapril strongly influences vasopressin content in important brain areas which are involved in central cardiovascular regulation. Therefore, central modulatory effects of ACE inhibitors may also contribute to overall therapeutic efficacy.
Colonoscopy, Tumors, and Inflammatory Bowel Disease - New Diagnostic Methods
Authors: R. Kiesslich, A. Hoffman, M. F. Neurath
Journal: Endoscopy (2006)

Accurate detection of premalignant lesions and early cancers in the colon is essential for curative endoscopic or surgical therapy, since the prognosis for the affected patients is closely related to the size and stage of the neoplastic lesion. Total colonoscopy is the accepted gold standard for screening and surveillance of colorectal cancer. This review summarizes recently published diagnostic developments and key findings in the areas of colonoscopy, colonic tumors, and inflammatory bowel diseases.Relevant findings have been reported for chromoendoscopy in the diagnosis of colitis-associated neoplasia, as well as flat and depressed adenomas. Real-time Doppler capabilities have now been added to endoscopic optical coherence tomography; the results of large-scale testing of narrow-band imaging endoscopy in the colon are being awaited; and fluorescence imaging has recently been added to the facilities available in video endoscopy. Most importantly, endomicroscopy now for the first time allows single-cell subsurface imaging during ongoing colonoscopy procedures, opening the way to in-vivo molecular and functional imaging.
Clinical Judgment versus the Laboratory
Authors: John A. Collins
Journal: New England Journal of Medicine (1982)

IT is often difficult to define the relative importance of clinical appraisal and laboratory evaluation of the sick patient. Much of the education of a clinician concerns this need to assign relative weights to evidence and to know when less is sufficient. In this issue of the Journal, Baker et al. attempt to accomplish this task for the nutritional assessment of hospitalized patients.1 Two clinicians seem to have performed as well as an array of laboratory tests, although the comparison, like all such efforts, was not without its problems. On one side were several clinical observers and a subjective . . .
National Study of Internal Medicine Manpower: XV. A Decade of Change in Residency Training in Internal Medicine
Authors: Ronald M. Andersen
Journal: Annals of Internal Medicine (1989)

We report on trends in the characteristics of residency training programs in internal medicine from 1976 to 1988 and make some comparisons with other specialties. Internal medicine is faring less well in the residency match compared with other specialties than it did 10 years ago. It has also increased the number of residency positions offered more than other major specialities. A sizable proportion of first-year residency positions in internal medicine are not filled through the Match. Foreign medical graduates account for almost 50% of the first-year resident (R1) positions filled outside the Match. Programs most dependent on foreign medical graduates are in hospitals with limited medical school affiliation, smaller size, operated by churches or the Veterans Administration, and located in eastern states and large metropolitan areas. Despite concerns about quality and oversupply, almost 50% of the program directors expected to increase the size of their programs in 1988-1990. Residents are not being scheduled for fewer hours per week than they were 12 years ago but they are being scheduled for fewer nights. No trends were noted toward increased ambulatory care training sites away from the hospital campus.
P915 PREDICTION OF RECURRENCE AFTER LIVER TRANSPLANTATION FOR HCC: VALIDATION OF THE AFP MODEL IN AN ITALIAN COHORT
Authors: A. Notarpaolo, G. Bizouard, M. Gambato, R. Montalti, G. Magini, L. Meglioresi, A. Vitale, G. Vennarecci, C. D'Ambrosio, P. Burra, F. Manenti, S. Fagiuoli, G.M. Ettore, A. Andreoli, U. Cillo, S. Katsahian, F. Roudot-Thoraval, C. Duvoux
Journal: Journal of Hepatology (2014)
Pattern of Ascending Aortic Dimensions Predicts the Growth Rate of the Aorta in Patients With Bicuspid Aortic Valve
Authors: Alessandro Della Corte, Ciro Bancone, Marianna Buonocore, Giovanni Dialetto, Franco E. Covino, Sabrina Manduca, Giancarlo Scognamiglio, Veronica D'Oria, Marisa De Feo
Journal: JACC. Cardiovascular imaging (2013)
TUMEFACTIVE LESIONS OF THE SMALL INTESTINE
Authors: C. ALLEN GOOD
Journal: JAMA (1941)

For many years the results of roentgenologic examination of the small intestine were unsatisfactory. Recent experience, however, leads one to believe that the accuracy of this method is nearly comparable to that which obtains in the roentgenologic examination of the stomach and colon. With the aid of proctoscopy and peroral endoscopy, the entire length of the alimentary canal now may be explored with confidence for the presence of disease. Although individual tumefactive lesions occur infrequently in the small intestine, in the aggregate they make up a fair proportion of all the pathologic conditions (excluding duodenal ulcer) encountered by the roentgenologist in this division of the gastrointestinal tract. These lesions include both neoplastic and non-neoplastic varieties. The granulomas or nonneoplastic tumefactions are due in most instances to chronic nonspecific enteritis or to tuberculosis. Granulomas caused by other inflammatory conditions such as actinomycosis, syphilis and lymphogranuloma venereum have been described but they
High-Risk Patients with Ventricular Preexcitation — A Pendulum in Motion
Authors: Bruce B. Lerman, Craig T. Basson
Journal: New England Journal of Medicine (2003)

Since they were first described, preexcitation syndromes have intrigued physicians. The interest derives in part from the myriad bizarre electrocardiographic abnormalities associated with these syndromes and from the variety of complex arrhythmias that may be manifested in affected patients. Symptomatic tachycardias develop in patients with the Wolff–Parkinson–White syndrome because there is conduction over an accessory (extranodal) atrioventricular pathway consisting of working myocardium. Since an impulse arising from the sinus node can activate the atrioventricular node and the more rapidly conducting accessory pathway in parallel, the ventricle ipsilateral to the site where the accessory pathway enters the myocardium is excited prematurely. . . .
Citalopram, Methylphenidate, or Their Combination in Geriatric Depression: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Helen Lavretsky, Michelle Reinlieb, Natalie St. Cyr, Prabha Siddarth, Linda M. Ercoli, Damla Senturk
Journal: American Journal of Psychiatry (2015)

Objective: The authors evaluated the potential of methylphenidate to improve antidepressant response to citalopram, as assessed by clinical and cognitive outcomes, in elderly depressed patients. Method: The authors conducted a 16-week randomized double-blind placebo-controlled trial for geriatric depression in 143 older outpatients diagnosed with major depression comparing treatment response in three treatment groups: methylphenidate plus placebo (N=48), citalopram plus placebo (N=48), and citalopram plus methylphenidate (N=47). The primary outcome measure was change in depression severity. Remission was defined as a score of 6 or less on the Hamilton Depression Rating Scale. Secondary outcomes included measures of anxiety, apathy, quality of life, and cognition. Results: Daily doses ranged from 20 mg to 60 mg for citalopram (mean=32 mg) and from 5 mg to 40 mg for methylphenidate (mean=16 mg). All groups showed significant improvement in depression severity and in cognitive performance. However, the improvement in depression severity and the Clinical Global Impressions improvement score was more prominent in the citalopram plus methylphenidate group compared with the other two groups. Additionally, the rate of improvement in the citalopram plus methylphenidate group was significantly higher than that in the citalopram plus placebo group in the first 4 weeks of the trial. The groups did not differ in cognitive improvement or number of side effects. Conclusions: Combined treatment with citalopram and methylphenidate demonstrated an enhanced clinical response profile in mood and well-being, as well as a higher rate of remission, compared with either drug alone. All treatments led to an improvement in cognitive functioning, although augmentation with methylphenidate did not offer additional benefits.