tbuckley/cabot-search huggingface dataset:
Topical phenylephrine increases anal canal resting pressure in patients with faecal incontinence
Authors: M J Cheetham
Journal: Gut (2001)

<h3>INTRODUCTION</h3> The internal anal sphincter receives a stimulatory alpha<sub>1</sub>adrenergic innervation. Use of an adrenergic agonist may therefore have a role in treating patients with faecal incontinence. <h3>METHODS</h3> Ten patients (seven females, median age 66 years) with passive faecal incontinence related to weak internal anal sphincter were studied. All patients had intact anal sphincters as assessed by endoanal ultrasound. Phenylephrine gel was applied in a double blind manner in concentrations of 0%, 10%, 20%, 30%, and 40% (Slaco Pharma (UK) Ltd, Watford, UK) on separate days. Maximum resting anal pressure (MRP), anodermal blood flow, blood pressure, and pulse rate were measured before, and one and two hours after application. <h3>RESULTS</h3> All concentrations of phenylephrine gel increased median MRP (43, 48, 54, 65, and 70 cm H<sub>2</sub>O, for placebo, 10% (p=0.122), 20% (p=0.170), 30% (p=0.002), and 40% (p=0.004), respectively at one hour; comparisons with placebo). This was sustained at two hours. There was a clear dose-response relationship at one hour. Higher concentrations raised median MRP to within the normal range (&gt; 60 cm H<sub>2</sub>O). At two hours, all concentrations greater than 20% increased the pressure to a similar degree, suggesting that the exact concentration may be important for the initial effect but given a certain threshold is less important after a period of time. Toxicity was rare. Two patients experienced transient perianal burning which settled within a few minutes. There was no significant effect on anodermal blood flow, blood pressure, or pulse rate. <h3>CONCLUSION</h3> This study has demonstrated the feasibility of using topical phenylephrine to raise resting anal tone in patients with faecal incontinence. Randomised controlled trials are required to assess the efficacy of this agent.
RECIPROCAL TRANSMISSION TESTS WITH INFECTIOUS CATARRH OF CHICKENS, MICE, AND RATS
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1942)

Infectious catarrh of chickens (fowl coryza of slow onset) was not transmissible to mice or rats by nasal instillation of the specific coccobacilliform bodies. Exudates were also inactive in both rodents on foot pad injection. The infectious catarrhs of the mouse and the rat were reciprocally transmissible by the nasal injection of exudates or tissue cultures of the respective coccobacilliform bodies and by direct contact. Exudates and cultures also produced an arthritic reaction in both hosts on foot pad injection. The coccobacilliform bodies of mouse catarrh were innocuous in chickens on nasal instillation, whereas those of rat catarrh were established locally but were maintained for only two passages. In the opposite host each of the two rodent forms of infectious catarrh reproduced the typical features of the naturally acquired disease, a highly fatal pneumonia being characteristic of the mouse but not of the rat.
The downside to lymphocytes
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

Lymphocytes are required to fight off invading microbes—T cells to seek out and kill infected cells, and B cells to produce pathogen-specific antibodies. But a study by Carrero and colleagues (page 933) suggests that, in some situations, having lymphocytes is not such a good thing.






Figure 1

Dying lymphocytes (red) inhibit the early clearance of L. monocytogenes (green) from the spleen.




Two decades ago, this group showed that lymphocyte-deficient mice are up to 1,000 times better than normal mice at controlling bacterial growth during the first few days of infection with Listeria monocytogenes. They speculated that mice born without lymphocytes might have developed a more efficient innate immune response—much like people who are born blind develop a heightened sense of smell and more acute hearing. This idea made sense because innate immune cells—such as macrophages and neutrophils—are responsible for killing the bacteria during the initial phase of infection.

But the speculation was incorrect. Macrophages from lymphocyte-deficient mice, they now show, are no more adept at killing the bug than those from normal mice. Nor do the deficient mice produce more inflammatory cytokines in response to infection. Instead, the explanation lay in another past observation: that infection with L. monocytogenes causes a massive death of lymphocytes.

This bug-induced cell death—which may allow the bacteria to establish an initial foothold in the host—was indeed to blame for the decreased clearance of the bug. When bone marrow-derived lymphocytes were transferred into deficient mice before infection, the transferred cells died and the mice were robbed of their heightened bug-killing ability.

The link between cell death and impaired bacterial control was traced to the antiinflammatory cytokine interleukin (IL)-10, which was produced in response to lymphocyte death. In mice lacking IL-10, infection still triggered lymphocyte death but early control of the bug was no longer inhibited. The IL-10 link is not surprising, as macrophage ingestion of apoptotic cells—which accumulate during all immune responses—is known to trigger the production of antiinflammatory cytokines, helping to resolve ongoing immune responses.

Although this study shows a downside to lymphocytes, it does not suggest that we would be better off without them. Indeed, although lymphocyte-deficient mice fare better in the short-term, without adaptive immunity the mice fail to clear the infection and the bacteria persist for life.
Impact of Achilles Tendon Lengthening on Functional Limitations and Perceived Disability in People With a Neuropathic Plantar Ulcer
Authors: Michael J. Mueller, David R. Sinacore, Mary Kent Hastings, Donovan J. Lott, Michael J Strube, Jeffrey E. Johnson
Journal: Diabetes Care (2004)

OBJECTIVE—An Achilles tendon-lengthening (ATL) procedure is effective at reducing ulcer recurrence in patients with diabetes, peripheral neuropathy, and a plantar ulcer, but its effects on functional limitations and perceived disability are unknown. The purpose of this study is to report the effects of an ATL and total contact casting (TCC) on the functional limitations and perceived disability of patients with neuropathic plantar ulcers. RESEARCH DESIGN AND METHODS—Twenty-eight subjects with a mean age of 55 ± 10 years and a BMI of 33 ± 6 kg/m2 participated. All subjects had a history of diabetes, loss of protective sensation, limited ankle motion, and a recurrent forefoot ulcer. Subjects were randomized into two groups: an ATL group (n = 14), who received treatment of ATL, and TCC and a TCC group (n = 14), who received TCC only. Subjects completed a modified physical performance test (PPT) and the SF-36 Health Survey before treatment, after primary treatment and healing of the plantar forefoot ulcer, and 8 months after initial ulcer healing. RESULTS—There were no significant changes in functional limitations as measured by the PPT between groups or over time. The physical summary score of the SF-36 decreased slightly from before treatment to 8 months after initial ulcer healing in the ATL group (35 ± 7 to 31 ± 6), whereas the TCC group score increased during this time (34 ± 8 to 39 ± 11; P &amp;lt; 0.05). CONCLUSIONS—The ATL resulted in no measurable change in functional limitations, but patients receiving an ATL and TCC reported lower physical functioning at 8 months after initial ulcer healing than subjects receiving TCC alone and may require additional physical therapy to address this perceived disability.
Insurance against injury in clinical trials
Authors: P I Reed
Journal: BMJ (1994)

Editor,--I support the views expressed by Anne Ferguson1 and wish to enlarge on them. The East Berkshire Research Ethics Committee sought legal advice on the question of seeking indemnity, not only for the health authority which appoints us but also for the trust, when a locally generated study is to take place. This advice concurred with our view that an indemnity in the format …
Epimorphin expression in intestinal myofibroblasts induces epithelial morphogenesis
Authors: Christine Fritsch, Elzbieta A. Swietlicki, Olivier Lefebvre, Michele Kedinger, Hristo Iordanov, Marc S. Levin, Deborah C. Rubin
Journal: Journal of Clinical Investigation (2002)

The formation of the crypt-villus axis during gut ontogeny requires continued reciprocal interactions between the endoderm and mesenchyme. Epimorphin/syntaxin 2 (epimorphin) is a mesenchymal protein expressed in the fetal gastrointestinal tract during villus morphogenesis. To elucidate its role in gut ontogeny, the epimorphin cDNA was transfected, in sense and antisense orientations, into a rat intestinal myofibroblast cell line, MIC 216. To determine the effects of epimorphin on the epithelium, myofibroblasts were cocultured with the Caco2 cell line. Caco2 cells spread in a simple monolayer over antisense-transfected cells lacking epimorphin. In contrast, sense-transfected myofibroblasts induced Caco2 cells to form compact, round clusters with small lumens. These morphologic differences were preserved in Transwell cocultures in which cell-cell contact was prevented, suggesting that epimorphin's effects were mediated by secreted factor(s). To determine the effects of epimorphin on crypt-villus axis formation in an in vivo model, rat gut endoderm was combined with epimorphin-transfected myofibroblasts and implanted into the chick intracoelomic cavity. The grafts in which epimorphin was overexpressed revealed multiple well-formed villi with crypt-like units, whereas those in which epimorphin expression was inhibited developed into round cystic structures without crypts or villi. Of several potential secreted morphogens, only the expression of bone morphogenetic protein 4 (Bmp4) was increased in the epimorphin-transfected cells. Incubation with noggin partially blocked the transfected myofibroblasts' effects on Caco2 colony morphology. These results indicate that mesenchymal epimorphin has profound effects on crypt-villus morphogenesis, mediated in part by secreted factor(s) including the Bmp's.
Development of Hepatitis B Vaccine
Authors: R. Palmer Beasley
Journal: JAMA (2009)

A highly purified and inactivated vaccine was made of hepatitis B virus surface antigen. The vaccine was tested exhaustively for safety by ordinary procedures and additionally in chimpanzees and marmosets. It was highly potent and induced antibody in guinea pigs, grivet monkeys, and chimpanzees after three doses of vaccine were given subcutaneously. Chimpanzees given three doses of vaccine were protected against challenge with 1000 chimpanzee-infectious doses of live human hepatitis B virus given intravenously in controlled studies. Tests of the vaccine for control of hepatitis B in man are to be carried out.See PDF for full text of the original JAMA article.
Epidemiologic Aspects of Gallbladder Cancer: A Case-Control Study of the SEARCH Program of the International Agency for Research on Cancer
Authors: W. A. Zatonski, K. Przewozniak, A. B. Lowenfels, P. Boyle, P. Maisonneuve, H. B. Bueno de Mesquita, C. J. Moerman, P. Ghadirian, A. Simard, M. Jain, G. R. Howe, P. Baghurst, A. J. McMichael, C. C. Hsieh, A. M. Walker
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: There are few previous epidemiologic studies of gallbladder cancer, a rare but nearly always lethal gastrointestinal cancer with a demonstrated greater frequency in adult women and older subjects of both sexes, and also in the members of populations throughout central and eastern Europe and certain racial groups such as native American Indians. Unfortunately, the prospects for the prevention of this form of cancer are poor. Purpose: Our purpose in conducting this study was to investigate possible new risk factors for gallbladder cancer and to strengthen our understanding of established causal agents that may be involved in this disease. Methods: A large, collaborative, multicenter, case-control study of cancer of the gallbladder was conducted in five centers located in Australia (Adelaide), Canada (Montreal and Toronto), The Netherlands (Utrecht), and Poland (Opole) from January 1983 through July 1988. Case subjects with gallbladder cancer were accrued by the centers from hospital pathology records and from reports to regional cancer registries. Cancer diagnosis was confirmed by either biopsy, cholecystectomy, or at the time of autopsy. Control subjects were randomly assigned at each center from the population. The pooled analysis included 196 case subjects and 1515 control subjects (who did not report previous cholecystectomy). Ninety-eight percent of the subjects were white. Personal interviews of case subjects, control subjects, and surrogates (spouse or next of kin) were conducted by trained personnel. Results: After adjusting for potential confounding factors (age, sex, center, type of interview, years of schooling, alcohol intake, and lifetime cigarette smoking), a history of gallbladder symptoms requiring medical attention (e.g., reduced bile secretion from the gallbladder into the small intestine due to obstructions of the common bile or cystic ducts) was the major risk factor associated with this form of cancer (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 2.6–7.5). This association was present even in subjects who had their first gallbladder examination because of symptoms present more than 20 years earlier (OR = 6.2; 95% CI = 2.8–13.4). Other variables associated with gallbladder cancer risk included an elevated body mass index, high total energy intake, high carbohydrate intake (after adjustment for total energy intake), and chronic diarrhea. All of these risk factors have been previously associated with gallstone disease. Conclusions: These findings are consistent with a major role of gallstones, or risk factors for gallstones, in the cause of gallbladder cancer. Additional information on whether or not screening high-risk subjects for gallstones or gallbladder cancer is needed.
Integrating cues in speech perception
Authors: Dominic W. Massaro
Journal: Behavioral and Brain Sciences (1998)

Sussman et al. describe an ecological property of the speech signal that is putatively functional in perception. An important issue, however, is whether their putative cue is an emerging feature or whether the second formant (F2) onset and the F2 vowel actually provide independent cues to perceptual categorization. Regardless of the outcome of this issue, an important goal of speech research is to understand how multiple cues are evaluated and integrated to achieve categorization.
Aerosol Pentamidine for Secondary Prophylaxis of AIDS-related <i>Pneumocystis carinii</i> Pneumonia
Authors: Julio S. G. Montaner, Lindsay M. Lawson, André Gervais, Robert H. Hyland, Charles K. Chan, Julian M. Falutz, Paolo M. Renzi, Douglas MacFadden, Anita R. Rachlis, I. W. Fong, Gary E. Garber, Andrew Simor, Norbert Gilmore, Mary Fanning, Geoffrey D. Taylor, Alain Y. Martel, Walter F. Schlech, Martin T. Schechter
Journal: Annals of Internal Medicine (1991)

Objective: To assess the safety and efficacy of aerosol pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Participants: Patients recovering from a first confirmed episode of AIDS-related P. carinii pneumonia who had no evidence of either another active AIDS-defining opportunistic infection or another pulmonary abnormality were considered eligible for the study but were included only if they had received no immunomodulators or antiretroviral agents other than zidovudine within 30 days of entry. One hundred sixty-two patients were randomized and started on the study drug. Intervention: Patients were randomly assigned to receive aerosol pentamidine, 60 mg per dose, or placebo, delivered using a hand-held, patient-triggered, ultrasonic nebulizer. The induction phase of treatment consisted of S doses over 14 days, followed by a maintenance phase beginning on day 21 and consisting of one dose every 2 weeks. Results: Thirty-two cases of P. carinii pneumonia were diagnosed before the termination of the trial; 27 cases occurred among 78 patients receiving placebo and S occurred among 84 patients receiving aerosol pentamidine. Estimates of the cumulative relapse rate of P. carinii pneumonia by 24 weeks were 50% and 9% for the placebo and pentamidine groups, respectively (P < 0.001). Adverse reactions attributed to the study drug occurred in 15 of 78 patients receiving placebo and in 28 of 84 patients receiving pentamidine (P = 0.04). These were all mild or moderate in severity and did not preclude continued administration of the study drug. Conclusion: Intermittent therapy with aerosol pentamidine is highly effective and well tolerated as secondary prophylaxis for AIDS-related P. carinii pneumonia.
P17.85 * LOW LEVELS OF HUMAN CYTOMEGALOVIRUS INFECTION IN GLIOBLASTOMA MULTIFORME ASSOCIATES WITH PATIENT SURVIVAL; A PROSPECTIVE STUDY
Authors: G. Stragliotto, A. Rahbar, J. Bartek, C. Soderberg-Naucler
Journal: Neuro-Oncology (2014)

BACKGROUND: Over 90% of GBM tumors have been shown to be infected with human cytomegalovirus (HCMV). In this study, we evaluated whether there was an association between the grade of HCMV infection and long-term survival in GBM patients. MATERIAL AND METHODS: Brain tumor tissue sections from consecutive GBMs patients operated at the Karolinska University Hospital from 2003 were analysed (n= 250). HCMV infection grade was determined by the number of HCMV positive cells negative (or grade 1-4) by immunohistochemistry. Chi-Square test and logistic regression analysis were used to assess an association between long-term survival and HCMV low-grade infection or other clinical prognostic parameters; age under 50 years, radical surgery or low recursive partition analysis (RPA) and MGMT status. RESULTS: HCMV infection was detected in tumor samples from 249 of 250 patients (99%). Forty percent of GBM patients who lived > 18 months had low-grade HCMV infection while only 8% GBM patients who lived < 18 months did. In the first 75 cases, multiple logistic regression analyses yielded an odds ratio estimate of 6.61 with 95% confidence interval (1.36-32.1) (p .019) for low grade HCMV after adjustment for RPA class, radical surgery, and age. CONCLUSION: We previously reported that low-grade HCMV infection was strongly associated with long-term survival in GBM patients in a case-control study of 75 patients. This larger prospective study of patients treated at a single institution confirms the previous data. As a consequence, CMV analysis by immunohistochemistry could be use as a prognostic marker in glioblastoma.
THE COURSE OF EXPERIMENTAL INFECTION OF THE CHICK EMBRYO WITH THE VIRUS OF EQUINE ENCEPHALOMYELITIS
Authors: Frederik B. Bang
Journal: The Journal of Experimental Medicine (1943)

The titration curve for the virus of Eastern equine encephalomyelitis inoculated into the 10 day old chick embryo shows that the maximum increase in virus content continues until shortly before the generalized destruction of the embryo is apparent. This is followed by a stationary phase. Histological studies of infected embryos fail to demonstrate selective tissue destruction, and titrations show the virus to be distributed throughout the egg, although concentrated in the embryo. The chorioallantoic membrane gradually becomes increasingly resistant with age to both the Eastern and Western viruses. Increased resistance with age is also apparent in the hatched chick. These findings are based on the use of the chick embryo itself as the test animal to determine the 50 per cent mortality end-point. The limits of accuracy of this method are defined.
(23) Von Recklinghausen's disease with involvement of the orbit and clavicle
Authors: G. Leigh, R.A. Marsden, G.M. Thompson
Journal: British Journal of Dermatology (1985)

Journal Article (23) Von Recklinghausen's disease with involvement of the orbit and clavicle Get access G. Leigh, G. Leigh ST George's Hospital, London SW17 Search for other works by this author on: Oxford Academic Google Scholar R.A. Marsden, R.A. Marsden ST George's Hospital, London SW17 Search for other works by this author on: Oxford Academic Google Scholar G.M. Thompson G.M. Thompson ST George's Hospital, London SW17 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Pages 66–67, https://doi.org/10.1111/j.1365-2133.1985.tb13038.x Published: 01 July 1985
Selective Constraints, Amino Acid Composition, and the Rate of Protein Evolution
Authors: Nicolas J. Tourasse, Wen-Hsiung Li
Journal: Molecular Biology and Evolution (2000)

What are the major forces governing protein evolution? A common view is that proteins with strong structural and functional requirements evolve more slowly than proteins with weak constraints, because a stringent negative selection pressure limits the number of substitutions. In contrast, Graur claimed that the substitution rate of a protein is mainly determined by its amino acid composition and the changeabilities of amino acids. In this paper, however, we found that the relative changeabilities of amino acids in mammalian proteins are different for transmembranal and nontransmembranal segments, which have very distinct structural requirements. This indicates that the changeability of a given residue is influenced by the structural and functional context. We also reexamined the relationship between substitution rate and amino acid composition. Indeed, the two kinds of segments exhibit contrasting amino acid compositions: transmembranal regions are made up mainly of hydrophobic residues (a total frequency of ∼60%) and are very poor in polar amino acids (<5%), whereas nontransmembranal segments have frequencies of 30% and 22%, respectively. Interestingly, we found that within a given integral membrane protein, nontransmembranal segments accumulate, on average, twice as many substitutions as transmembranal regions. However, regression analyses showed that the variability in amino acid frequencies among proteins cannot explain more than 30% of the variability in substitution rate for the transmembranal and nontransmembranal data sets. Furthermore, transmembranal and nontransmembranal segments evolving at the same rate in different proteins have different compositions, and the compositions of slowly evolving and rapidly evolving segments of the same type are similar. From these observations, we conclude that the rate of protein evolution is only weakly affected by amino acid composition but is mostly determined by the strength of functional requirements or selective constraints.
Appendicular Bone Density and Age Predict Hip Fracture in Women
Authors: Steven R. Cummings
Journal: JAMA (1990)

To determine whether measurement of bone density predicts hip fracture in women, we prospectively studied 9703 nonblack women aged 65 years and older who had measurements of bone mineral density using single-photon absorptiometry in the calcaneus, distal radius, and proximal radius. During an average of 1.6 years of follow-up, 53 hip fractures occurred. The risk of hip fracture was inversely related to bone density at all three measurement sites. After adjusting for age, the relative risk of hip fracture was 1.66 for a decrease of 1 SD in the bone density at the calcaneus (95% confidence interval, 1.22 to 2.26), 1.55 (95% confidence interval, 1.13 to 2.11) at the distal radius, and 1.41 (95% confidence interval, 1.06 to 1.88) at the proximal radius. None of the three measurements was a significantly better predictor of hip fracture than the others. After adjusting for bone mineral density, the risk of hip fracture doubled for each 10-year increase in age (relative risk, 2.09; 95% confidence interval, 1.31 to 3.33). We conclude that decreased bone density in the appendicular skeleton is associated with an increased risk of hip fracture, but this accounts for only part of the age-related increase in risk of hip fracture among older women. (<i>JAMA</i>. 1990;263:665-668)