tbuckley/cabot-search huggingface dataset:
Silent Brain Infarcts and the Risk of Dementia and Cognitive Decline
Authors: Sarah E. Vermeer, Niels D. Prins, Tom den Heijer, Albert Hofman, Peter J. Koudstaal, Monique M.B. Breteler
Journal: New England Journal of Medicine (2003)

Silent brain infarcts are frequently seen on magnetic resonance imaging (MRI) in healthy elderly people and may be associated with dementia and cognitive decline.We studied the association between silent brain infarcts and the risk of dementia and cognitive decline in 1015 participants of the prospective, population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia and stroke at base line. Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period. We performed Cox proportional-hazards and multiple linear-regression analyses, adjusted for age, sex, and level of education and for the presence or absence of subcortical atrophy and white-matter lesions.During 3697 person-years of follow-up (mean per person, 3.6 years), dementia developed in 30 of the 1015 participants. The presence of silent brain infarcts at base line more than doubled the risk of dementia (hazard ratio, 2.26; 95 percent confidence interval, 1.09 to 4.70). The presence of silent brain infarcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function. Silent thalamic infarcts were associated with a decline in memory performance, and nonthalamic infarcts with a decline in psychomotor speed. When participants with silent brain infarcts at base line were subdivided into those with and those without additional infarcts at follow-up, the decline in cognitive function was restricted to those with additional silent infarcts.Elderly people with silent brain infarcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions.
Progesterone, fluid, and electrolytes in premenstrual syndrome.
Authors: P M O'Brien, C Selby, E M Symonds
Journal: BMJ (1980)

Changes in mood, plasma progesterone concentration, urinary volume, sodium excretion, sodium:potassium ratio, and body weight during the menstrual cycle were determined in 18 women with premenstrual syndrome and 10 symptomless (control group) women. Plasma progesterone concentration was higher in the women with symptoms during the postovulatory phase of the cycle, and the peak progesterone concentration appeared earlier. The changes in progesterone concentration were accompanied by a natriuresis and diuresis that fell towards preovulatory values in the premenstrual phase. Sodium retention was not confined to any definite period. Mood symptoms occurred after the changes in progesterone and electrolyte concentrations. Progesterone deficiency is probably not the cause of premenstrual syndrome. Thus treatment with progesterone is probably illogical unless a deficiency is detected. Treatment should be aimed at preventing the natriuretic effect of progesterone in the postovulatory phase and the sodium-retaining and water-retaining effects of aldosterone in the premenstrual phase.
Emergence of tick-borne encephalitis in new endemic areas in Austria: 42 years of surveillance
Authors: F X Heinz, K Stiasny, H Holzmann, M Kundi, W Sixl, M Wenk, W Kainz, A Essl, C Kunz
Journal: Eurosurveillance (2015)

Human infections with tick-borne encephalitis (TBE) virus are a public health concern in certain regions of Europe, central and eastern Asia. Expansions of endemic areas and increased incidences have been associated with different factors including ecological changes supporting tick reproduction, socioeconomic changes increasing human outdoor activities and climatic changes favouring virus circulation in natural foci. Austria is among the most strongly affected countries in Central Europe, but the annual number of cases has strongly declined due to vaccination. Here, we have analysed changes of the incidence of TBE in the unvaccinated population of all federal states of Austria over a period of 42 years. The overall incidence in Austria has remained constant, but new strongly affected endemic regions have emerged in alpine valleys in the west of Austria. In parallel, the incidence in low-land regions in the north-east of the country is decreasing. There is no evidence for a shift to higher altitudes of infection sites in the traditional TBE zones, but the average altitudes of some newly established endemic areas in the west are significantly higher. Our analyses underscore the focal nature of TBE endemic areas and the potential of TBE virus to emerge in previously unaffected regions.
Serologic Association Between Human Papillomavirus Type 16 Infection and Esophageal Cancer in Shaanxi Province, China
Authors: C. Han, G. Qiao, N. L. Hubbert, L. Li, C. Sun, Y. Wang, M. Yan, D. Xu, Y. Li, D. R. Lowy, J. T. Schiller
Journal: JNCI Journal of the National Cancer Institute (1996)

The existence of large geographic variations in the prevalence of esophageal cancer in some countries, such as China, indicates that environmental risk factors may be important in the development of this disease. Some studies have implicated genital-mucosal strains of human papillomaviruses (HPVs) in the etiology of this cancer. We conducted a case-control study in Shaanxi Province, China, an area with a population at high risk for esophageal cancer, to assess the association of this disease with infection by HPV type 16 (HPV16), the most common cancer-associated genital-mucosal HPV type. Ninety individuals with esophageal cancer and 121 cancer-free control subjects were identified among the patients in two hospitals in Xi'an, Shaanxi Province. The control subjects were matched to the case patients on the basis of age and sex. Blood specimens were drawn from all study subjects, and serum was isolated by routine methods. The presence of HPV16 antibodies in serum samples was determined by use of an enzyme-linked immunosorbent assay (ELISA) that used baculovirus-derived HPV16 virus-like particles as the antigen. A similar ELISA that used bovine papillomavirus type 1 (BPV1) virus-like particles as the antigen controlled for the specificity of HPV16 seroreactivity. Data from the HPV16 and the BPV1 assays were normalized with respect to results obtained in each assay with a control serum of known HPV16 seroreactivity. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to examine the association between HPV16 seroreactivity and esophageal cancer. Reported P values are two-sided. The mean seroreactivity to HPV16 virus-like particles was significantly higher for the cancer patients than for the control subjects (mean value±standard deviation = 0.85± 0.22 versus 0.74±0.18; P <.0001). When the cancer patients and control subjects were compared by sex and age groups, the differences in mean seroreactivity remained statistically significant. The difference in mean seroreactivity to BPV1 virus-like particles between cancer patients and control subjects was not statistically significant (0.81± 0.28 versus 0.88 ± 0.32; P = .12); this result was not altered when sex and age groups were compared. By use of a cutoff point for HPV16 seropositivity that was established in studies of cervical neoplasia, 24% of the cancer patients were seropositive compared with 7% of the control subjects, yielding a sexand age-adjusted OR of 4.5 (95% CI = 1.8–11.9). In general, the OR for esophageal cancer increased with increasing HPV16 seroreactivity. HPV16 infection may be a risk factor for esophageal cancer. Further studies of the association between HPV16 infection and the incidence of esophageal cancer are needed.
Recognition of a Purified &lt;italic&gt;M&lt;/italic&gt;&lt;sub&gt;r&lt;/sub&gt;-40,000 Organ-Specific Immunogen of Human Lung Cancer by Class II-Restricted T-Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: D M Thomson, M Sutherland, R Scanzano, G Shenouda
Journal: JNCI Journal of the National Cancer Institute (1987)

An Mr-40,000 polypeptide (p40) was purified from a lung cancer cell line on the basis of its antigenicity with leukocytes from lung cancer patients in an in vitro immunological assay of leukocyte adherence inhibition. Here, the cells and mechanism responsible for recognizing the purified p40 organ-specific cancer neoantigen (OSN) were studied. Buffy coat leukocytes from lung cancer patients showed a bell-shaped dose response with a peak response at 0.75 micrograms/assay. Mononuclear cells showed a similar response pattern, whereas pure T-cells were unreactive. Monoclonal antibodies (MAbs) to T-cell differentiation antigens T3 and T4 inhibited the response in a dose-dependent fashion, whereas anti-T8 had no effect, indicating T helper cells and their T3-antigen receptor complex recognized the antigen. MAbs to class II major histocompatibility complex (MHC) antigens also inhibited the response, whereas MAbs to class I MHC had no effect, indicating an important role for class II MHC antigens of monocytes. None of the MAbs inhibited the response to OSN on membrane fragments, which is mediated by antibody-dependent monocytes. Trypsin- or cyanogen bromide-cleaved p40 OSN triggered a response at the same concentrations as the intact molecule. The p40 OSN incubated with live leukocytes showed less than 30% proteolytic digestion. The results indicate that class II-restricted T-cells recognize, via their antigen-specific cell surface receptors, contiguous sequences within the immunogenic tumor molecule in the context of the molecule or peptides binding to class II transplantation antigens.
Late-breaking abstract: Hypersensitivity pneumonitis in hairdressers
Authors: Øistein Svanes, Jorunn Kirkeleit, Tor B Aasen, Lene Svendsen, Torgeir Storaas, Randi Bertelsen, Cecilie Svanes
Journal: European Respiratory Journal (2014)

Specific inhalation challenge (SIC) is a well-established method for diagnosis of occupational asthma caused by persulphate salts in hairdressers. In 8 of 14 hairdressers investigated with SIC we saw a clinical pattern more consistent with hypersensitivity pneumonitis (HP) than asthma. We describe two hairdressers with SIC-findings consistent with a diagnosis of HP.   Methods:  The patients were challenged on two subsequent days with 10 minutes exposure for 0g (placebo), 5g, 15g and 30g potassium persulphate mixed with 150g lactose.   Results:  Both patients were non-smoking young women with no history of asthma or allergy and negative specific IgEs. They had experienced repeated work-related episodes of flu-like symptoms, cough and dyspnoea, but not wheezing episodes. In response to persulphate challenge,  case 1  got flu-like symptoms, 10% decrease in diffusion capacity for carbon monoxide (DLCO) after 4-5 hours, temperature increase from 36.4 to 37.4 after 12 hours, and 17% decrease in FEV 1  after 23 hours.  Case 2  responded with flu-like symptoms and shoulder joint pains, temperature increase from 36.5 to 37.3 after 8 hours, 18% decrease in FEV 1  after 9 hours, and 35-40% increase in leucocytes. Metacholine challenge test before and after SIC were negative for both cases.   Conclusion:  In two hairdressers suspected of having persulphate-induced asthma, we found little evidence of current asthma, but following SIC they both presented with flu-like symptoms, temperature rise, and leucocytosis or reduced DLCO. This reaction suggests a specific immunologic reaction more peripherally in the lungs, and is compatible with, though not definitively diagnostic of, hypersensitivity pneumonitis (Munoz, X. et al. CurrOpinAllergy ClinImmunol 2013; 13:151-8).
Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 Increases Neovascularization and Blood Flow Recovery After Ischemia
Authors: Sabine M.J. Welten, Antonius J.N.M. Bastiaansen, Rob C.M. de Jong, Margreet R. de Vries, Erna A.B. Peters, Martin C. Boonstra, Søren P. Sheikh, Nicola La Monica, Ekambar R. Kandimalla, Paul H.A. Quax, A. Yaël Nossent
Journal: Circulation Research (2014)

Rationale: Effective neovascularization is crucial for recovery after cardiovascular events. Objective: Because microRNAs regulate expression of up to several hundred target genes, we set out to identify microRNAs that target genes in all pathways of the multifactorial neovascularization process. Using www.targetscan.org , we performed a reverse target prediction analysis on a set of 197 genes involved in neovascularization. We found enrichment of binding sites for 27 microRNAs in a single microRNA gene cluster. Microarray analyses showed upregulation of 14q32 microRNAs during neovascularization in mice after single femoral artery ligation. Methods and Results: Gene silencing oligonucleotides (GSOs) were used to inhibit 4 14q32 microRNAs, miR-329, miR-487b, miR-494, and miR-495, 1 day before double femoral artery ligation. Blood flow recovery was followed by laser Doppler perfusion imaging. All 4 GSOs clearly improved blood flow recovery after ischemia. Mice treated with GSO-495 or GSO-329 showed increased perfusion already after 3 days (30% perfusion versus 15% in control), and those treated with GSO-329 showed a full recovery of perfusion after 7 days (versus 60% in control). Increased collateral artery diameters (arteriogenesis) were observed in adductor muscles of GSO-treated mice, as well as increased capillary densities (angiogenesis) in the ischemic soleus muscle. In vitro, treatment with GSOs led to increased sprout formation and increased arterial endothelial cell proliferation, as well as to increased arterial myofibroblast proliferation. Conclusions: The 14q32 microRNA gene cluster is highly involved in neovascularization. Inhibition of 14q32 microRNAs miR-329, miR-487b, miR-494, and miR-495 provides a promising tool for future therapeutic neovascularization.
Our Invisible Patients
Authors: Sharon Manne
Journal: Journal of Clinical Oncology (2005)

During my fellowship training and early career, I was a pediatric psychologist providing psychiatric liaison to the Pediatric Oncology Unit at the Memorial Sloan-Kettering Cancer Center (New York, NY). The majority of the referrals were for children exhibiting behavioral problems such as severe tantrums, inability to swallow pills or refusal to eat, anxiety during invasive procedures, and other problems with adherence to medical treatment. My work sometimes involved teaching children coping skills or assessing the underlying emotional problem for the behavioral issues. But in the majority of cases, I worked with parents to teach them behavioral methods to handle these problems. As I worked closely with families, I usually followed the patient—and the family—for the entire duration of the child’s treatment, whether it was successful or not.
REVERSAL OF TRANSPLANT REJECTION BY MONOCLONAL ANTIBLAST ANTIBODY
Authors: H. Takahashi, P.I. Terasaki, T. Kinukawa, D. Chia, K. Miura, H. Okazaki, Y. Iwaki, Y. Taguchi, S. Hardiwidjaja, M. Ishizaki, R. Billing
Journal: The Lancet (1983)
Diarrhoea and weight loss in an immunosuppressed patient
Authors: S. Al-shamma, M. Fox, F. Campbell, P. Collins, M. Lombard
Journal: Gut (2010)

A 74-year-old Caucasian female presented with a 12 month history of non-bloody, culture-negative diarrhoea associated with weight loss of 10 kg. She denied any extragastrointestinal manifestations. She had previously undergone orthotopic liver transplantation for primary biliary cirrhosis 12 years ago. Her immunosuppression was mycophenolate mofetil 500 mg twice daily for the past 2 years. She had previously been on ciclosporin but this was discontinued due to renal impairment.

Baseline bloods revealed: haemoglobin 9.6 g/dl (mean corpuscular volume (MCV) 85 fl), C-reactive protein 76 mg/l and normal renal and liver biochemistry. She was euthyroid, and coeliac serology was negative. Colonoscopy demonstrated moderate, patchy mucosal inflammation predominantly affecting the proximal colon (figure 1). Multiple biopsies were obtained.



Figure 1 
Ascending colon.



What is the diagnosis?

What is the best management?

See page 1302 for the answers 

From the questions on page …
IL-6 Trans-Signaling Drives Murine Crescentic GN
Authors: Gerald S. Braun, Yoshikuni Nagayama, Yuichi Maruta, Felix Heymann, Claudia R. van Roeyen, Barbara M. Klinkhammer, Peter Boor, Luigi Villa, David J. Salant, Ute Raffetseder, Stefan Rose-John, Tammo Ostendorf, Jürgen Floege
Journal: Journal of the American Society of Nephrology (2015)

The role of IL-6 signaling in renal diseases remains controversial, with data describing both anti-inflammatory and proinflammatory effects. IL-6 can act via classic signaling, engaging its two membrane receptors gp130 and IL-6 receptor (IL-6R). Alternatively, IL-6 trans-signaling requires soluble IL-6R (sIL-6R) to act on IL-6R-negative cells that express gp130. Here, we characterize the role of both pathways in crescentic nephritis. Patients with crescentic nephritis had significantly elevated levels of IL-6 in both serum and urine. Similarly, nephrotoxic serum-induced nephritis (NTN) in BALB/c mice was associated with elevated serum IL-6 levels. Levels of serum sIL-6R and renal downstream signals of IL-6 (phosphorylated signal transducer and activator of transcription 3, suppressor of cytokine signaling 3) increased over time in this model. Simultaneous inhibition of both IL-6 signaling pathways using anti–IL-6 antibody did not have a significant impact on NTN severity. In contrast, specific inhibition of trans-signaling using recombinant sgp130Fc resulted in milder disease. Vice versa, specific activation of trans-signaling using a recombinant IL-6–sIL-6R fusion molecule (Hyper-IL-6) significantly aggravated NTN and led to increased systolic BP in NTN mice. This correlated with increased renal mRNA synthesis of the Th17 cell cytokine IL-17A and decreased synthesis of resistin-like alpha (RELMalpha)-encoding mRNA, a surrogate marker of lesion-mitigating M2 macrophage subtypes. Collectively, our data suggest a central role for IL-6 trans-signaling in crescentic nephritis and offer options for more effective and specific therapeutic interventions in the IL-6 system.
Effect of oxygen on breathing irregularities during haemodialysis in patients with chronic uraemia
Authors: JC Yap, YT Wang, SC Poh
Journal: European Respiratory Journal (1998)

Hypoxaemia and breathing irregularities have been shown to occur during haemodialysis in patients with chronic renal failure. This study examined the role of hypoxia in the genesis of the irregular breathing during haemodialysis. The ventilatory patterns using respiratory inductance plethysmography and arterial blood gases were studied in seven males with chronic renal failure on long-term haemodialysis. The study was carried out before and during dialysis on one day without (D1) and another day with intranasal oxygen at 4 L x min(-1) (D2). On D1, mean (SD) arterial oxygen tension (Pa,O2) fell 1.9 (0.9) kPa (p<0.001) and mean minute ventilation (V'E) fell 1.9 (1.1) L x min(-1) (p<0.01) during dialysis. The arterial carbon dioxide tension (Pa,CO2) did not show a significant decrease (4.7 (0.2) kPa before and 4.6 (0.2) kPa during dialysis). Cumulative number of apnoeas was 64 and the coefficients of variation (COV) of respiratory frequency (fR) and tidal volume (VT) were 29.6 (11.9) and 38.2 (11.9)%, respectively. On D2, mean Pa,O2 remained stable (20.4 (4.1) kPa before, 21.3 (4.1) kPa during dialysis). There was no significant change in mean V'E (6.4 (0.9) L x min(-1) before, 5.5 (0.5) L x min(-1) during dialysis). Pa,CO2 decrease was not significant but the fall was greater (4.8 (0.1) kPa before, 45 (0.5) kPa during dialysis). Cumulative number of apnoeas was 94 and the COVs offR and VT were 35.8 (5.1) and 40.5 (11.3)%, respectively. Oxygen administration did not significantly affect the haemodialysis-induced changes in ventilation and breathing pattern, despite a significant protective effect from the fall in arterial oxygen tension. It was concluded that the fall in arterial oxygen tension is not the main determinant of breathing irregularities during haemodialysis.
EU report shows massive increase in legal highs
Authors: R. Watson
Journal: BMJ (2015)

New psychoactive substances, dubbed “legal highs,” came on the market across the European Union at the rate of almost two a week last year, says an annual report from the European Monitoring Centre for Drugs and Drug Addiction, based in Portugal.1

In addition to the 101 such substances reported to the EU’s early warning system a further 41 have already been identified this year, bringing to more than 450 the number of substances the centre is monitoring. Some two thirds came from two groups: synthetic cathinones and synthetic cannabinoids, which are sold …
ANTIGENIC RELATIONSHIPS BETWEEN GROUPS B AND G STREPTOCOCCI
Authors: Stephen N. Curtis, Richard M. Krause
Journal: The Journal of Experimental Medicine (1964)

Trypsinized cell walls of Group B hemolytic streptococci are composed of a group-specific carbohydrate and mucopeptide. The carbohydrate extracted with hot formamide is composed of rhamnose, N-acetylglucosamine, and galactose. Quantitative precipitin inhibition studies have shown that L rhamose is the significant component of the antigenic determinant. The cross-reactivity between B and G carbohydrates is dependent upon the fact that Lrhamose is a determinant sugar in both antigens.
Effect of dopamine infusion on gastric and pancreatic secretion and on gastrin release in man.
Authors: R Caldara, C Ferrari, M Romussi, L Bierti, S Gandini, G Curtarelli
Journal: Gut (1978)

The effect of dopamine infusion on basal and pentagastrin-stimulated gastric secretion, on basal and secretin-CCK-PZ-stimulated pancreatic secretion, and on basal and meal-induced gastrin release has been evaluated in healthy volunteers. Both basal and stimulated gastric acid secretion were significantly inhibited during dopamine infusion with a significant rebound to pre-infusion values after discontinuing dopamine. These effects were prevented by pretreatment with the antidopaminergic drug, metoclopramide. A slight but now significant decrease in amylase and bicarbonate outputs was also observed during dopamine infusion, while gastrin release did not change. These data suggest the existence of dopaminergic mechanisms in the regulation of gastric acid secretion in man.