tbuckley/cabot-search huggingface dataset:
A longitudinal study of Alzheimer's disease: measurement, rate, and predictors of cognitive deterioration
Authors: R G Stern, R C Mohs, M Davidson, J Schmeidler, J Silverman, E Kramer-Ginsberg, T Searcey, L Bierer, K L Davis
Journal: American Journal of Psychiatry (1994)

This study measured the annual rate of cognitive change in patients with Alzheimer's disease and determined the effects of clinical variables on that rate. It also compared the ability of two cognitive scales to measure change over the entire range of dementia severity.The cognitive subscale of the Alzheimer's Disease Assessment Scale and the Blessed test for information memory and concentration were given to 111 patients with Alzheimer's disease and 72 nondemented elderly comparison subjects at 6-month intervals for up to 90 months. Longitudinal changes in scores on the cognitive subscale were measured with several different methods of data analysis.For the patients with Alzheimer's disease, the annual rate of change in cognitive subscale scores showed a quadratic relationship with dementia severity in which deterioration was slower for mildly and severely demented patients than for patients with moderate dementia. Gender, age at onset, and family history of dementia had no effect on the rate of cognitive deterioration. The comparison group showed a slight improvement in cognitive performance over time. All data analytic methods gave similar results. The cognitive subscale of the Alzheimer's Disease Assessment Scale was more sensitive to change in both mild and severe dementia than was the Blessed test.These results suggest that cognitive deterioration is slow during the early and very late stages of Alzheimer's disease and more rapid during the middle stages. No clinical variables other than degree of cognitive impairment and previous rate of cognitive decline predicted rate of deterioration. These results have implications for treatment trials and attempts to identify subgroups.
P-Wave Morphology in Focal Atrial Tachycardia
Authors: Peter M. Kistler, Kurt C. Roberts-Thomson, Haris M. Haqqani, Simon P. Fynn, Suresh Singarayar, Jitendra K. Vohra, Joseph B. Morton, Paul B. Sparks, Jonathan M. Kalman
Journal: Journal of the American College of Cardiology (2006)
Abstract 5940: Central Sympatholysis With Dexmedetomidine is an Effective Countermeasure for Cocaine-Induced Sympathetic Activation and Peripheral Vasoconstriction in Chronic Cocaine Abusers
Authors: Andrew C Kontak, Zhongyun Wang, Debbie Arbique, Ronald G Victor
Journal: Circulation (2009)

Cocaine has been shown to stimulate the human cardiovascular system by acting primarily in the brain to increase sympathetic nerve activity to the peripheral circulation. In healthy cocaine naive ...
Genetic polymorphisms in early and late-onset bronchial asthma
Authors: Mayra Parra Pérez, Marta Ferrer Galván, Verónica Sánchez López, Auxiliadora Romero Falcón, Juan Francisco Medina Gallardo, Pilar Pérez Morilla, Pablo Pérez Navarro, Francisco Javier Álvarez Gutiérrez
Journal: European Respiratory Journal (2014)

Introduction: Polymorphism ofglutathione s-transferase (GST) seem to play a role as genetical causes in the development of asthma, though earlier studies failed to demonstrate a relation between GST subclasses: GSTM1 (Glutathione S-transferase Mu 1), GSTT1 (Glutathione S-transferase theta-1) y GSTP1.5 (Glutathione S-transferase P) and asthma.

Aims: We compared polymorphisms of GST in patients with early-onset asthma in infants, as well as in adults with late-onset asthma.

Methods: We analyzed two cohorts of patients with asthma. One cohort included patients who developed asthma before the age of 12 years. The second cohort patients presented symptoms of asthma after the age of 20 years. We extracted DNA from blood samples. GST subtypes GSTT1, GSTM1 y GSTP1.5 were detected using Polymerase Chain Reaction (PCR). For GSTP1.5 we later realized restriction

Results: Total of 83 patients, mean age 36 (±13) years. 43 female, 39 male. 84% of patients were atopics. 72% presented rhinitis, 17% atopic dermatitis.

In 40 patients onset of asthma was described before the age of 12 (mean age during survey 30(±12) years). 43 patients diagnosed with asthma after the age of 20 (mean age of onset 32(±10) years, mean current age 43(±12) years). We found significant correlation (p<0,011) between GSTM1 and early-onset asthma in 65% (26) of patients versus 37, 1% (16) in patients with late-onset asthma. There was no difference in the frequencies of GSTT1 and GSTP1.5.

Conclusions: We found significant correlation between GSTM1 (null genotype) and early-onset asthma, suggesting an important genetical component in the development of asthma during infancy.
Seasonality of birth in children with diabetes
Authors: H. Zhao
Journal: BMJ (2000)

Editor—Rothwell et al have found evidence for seasonality of birth in children with diabetes from Great Britain but not elsewhere.1 They do not, however, give ascertainment estimates for the centres participating in the study. Consequently, selection bias may play a part in their results, particularly in those centres with low case ascertainments.

Although this is a large multicentre study, the authors have not analysed the pooled data. They point out that sample sizes from many centres were too small to provide enough power for the seasonality of birth in these children to be assessed. It would be interesting to know if the analysis of the pooled data still showed a significant pattern.

The authors have previously shown evidence of seasonality of birth in children with diabetes in Scotland, Yorkshire, and England and Wales.2 In contrast, the current report shows no evidence for this effect in children born in England and Wales, although the χ2 value is greater than the one quoted in their previous paper. It is difficult to reconcile these two sets of data.

Rothwell et al also state that a similar pattern has been found in the Netherlands.3 The authors who reported the study there found that more boys with diabetes were born in April, May, and November but did not find an effect either for girls or for boys and girls combined.3 In contrast, Rothwell et al report a significant seasonal pattern of birth, with a peak in early summer and a trough in winter.1,2 The pattern in Britain is clearly different from that in the Netherlands.

We have examined this phenomenon by the same methodology in our local register, the Cornwall and Plymouth children's diabetes register.4 Children diagnosed with type 1 diabetes under the age of 16 were enrolled in our register, with 94.4% ascertainment. The analysis was of 417 children with diabetes born between 1970 and 1995. Our results showed that no significant seasonality of birth exists in the south west of England (χ2=4.05, df=2, P=0.13). This result is in line with results from Sardinia5 and some other European countries1 but is contrary to the results presented by Rothwell et al. In our opinion, the evidence derived from such registers and its support for the environmental cause of childhood diabetes need to be assessed further.
Enhanced radiosensitization by cepharanthin through the inhibition of NF-κB in human oral squamous carcinoma cells
Authors: Tetsuya Tamatani, Masayuki Azuma, Katsumi Motegi, Natsumi Takamaru, Mitsunobu Sato
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4422 

[Background] We have already demonstrated that human head and neck cancer cells have a significantly enhanced activity of the transcription factor NF-κB as compared to their normal counterparts, suggesting that NF-κB plays an important role in the development of head and neck cancer. However, it has been reported that chemotherapeutic agents and radiotherapy activate NF-κB activity in carcinoma cells, leading to the acquisition of an anti-apoptosis, angiogenesis, and cell growth. In addition, we have shown that the suppression of NF-κB activity enhanced the apoptosis in oral squamous carcinoma cells. [Purpose] In this study, we examined whether inhibition of NF-κB activity by cepharanthin would enhance the radiosensitization in human oral carcinoma cells (B88, BHY, and HNt cells) [Method and Results] Cepharanthin (donated by Kaken Pharmaceutical Inc., Osaka, Japan) is a biscoclaurine alkaloid extracted from the roots of Stephania cepharantha hayata, and is widely used in Japan for the treatment of patients with leucopenia, nasal allergy, and venomous snake bites. γ-irradiation(IR) induced the NF-κB activity in oral carcinoma cells through the activation of the up-streams molecules, including Akt, IKK, and IκBα. However, luciferase assay revealed that cepharanthin suppressed the IR-induced NF-κB activity in oral squamous carcinoma cells, which resulted in the enhanced radiosensitization. Western blot analysis showed an enhanced cleavage of PARP protein in carcinoma cells by both treatment with cepharanthin and exposure to IR compared to IR or cepharanthin alone. In vivo study, B88 cells were s.c. inoculated into the backs of nude mice. Tumor-bearing nude mice received either cepharanthin (i.p., three times/week) or IR alone (1.5 Gy /day, five times/week) or combination of cepharanthin and IR. The tumor growth was significantly suppressed by treatment with combination of cepharanthin and IR compared with cepharanthin or IR alone. Cepharanthin inhibited the production of IR (7.5 and 15 Gy)-induced IL-6 and IL-8, which are down-stream targets of NF-κB. Quantitative real-time RT-PCR indicated that IR also induced the expression of the anti-apototic proteins (cIAP-1, and -2) in carcinoma cells. Treatment with cepharanthin and exposure to IR of cancer cells caused the decrease in the expression of cIAP-1, and -2 mRNAs. [Conclusions] These findings suggested that combination of radiotherapy with cepharanthin could lead to the enhancement of radiosensitization in the treatment of human oral cancer.
Service can't cope with troughs in demand, let alone peaks
Authors: R. Kishen
Journal: BMJ (1996)

7.6 cases in the month after immunisation in the United Kingdom, based on the typical reported annual incidence of 1/100 000 ).1We questioned 103 patients with Guillain- Barre or Miller Fisher syndrome, 98 household controls, and 93 hospital controls in south east England in 1992-4 (before the measles/rubella immunisation programme).2Thirteen patients, and nine household and five hospital controls reported being immunised within 12 weeks before onset of neuropathy in the index case.The immunisations were for influenza in 10 patients and eight household and three hospital controls, typhoid/cholera in one patient and one household control, typhoid alone in one patient, tetanus toxoid booster in one patient, diphtheria/ tetanus/pertussis in one hospital control, and
Abstract 246: Phase 1 study: Ipilimumab (anti CTLA-4) in combination with Lenalidomide in patients with advanced cancers
Authors: Divya Sakamuri, Sonia L. Betancourt Cuellar, Isabella C. Glitza, Siqing Fu, Jennifer J. Wheler, Gerald S. Falchook, Apostolia M. Tsimberidou, David S. Hong, Vivek Subbiah, Michelle A. Fanale, Maria E. Cabanillas, Funda Meric-Bernstam, Filip Janku
Journal: Cancer Research (2015)

Abstract Background: Ipilimumab, a cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibody potentiates an antitumor T-cell response. Lenalidomide, a derivative of thalidomide possesses immunomodulatory, antiangiogenic, and antineoplastic properties and thereby inhibits the growth of blood vessels and exhibits an anti-inflammatory effect. The potential synergistic effect of stimulating one's own immune system to attack cancer in combination with depriving further tumor growth provides rationale for combining Ipilimumab and Lenalidomide. Methods: We designed a phase I study (3+3 design) to determine the safety of Ipilimumab (1.5-3mg/kg IV q 28 days x 4) and Lenalidomide (10-25mg PO daily x 21 q 28 days) until disease progression or unacceptable toxicity in advanced cancers. Endpoints included maximum tolerated (MTD), dose limiting toxicities (DLT), safety, and response per immune response criteria (iRC). Results: To date, 21 patients (men, n = 8; women, n = 13), median age 56 (19-75) years, median of 3 (0-6) prior therapies (including 3 patients with prior ipilimumab) were enrolled in 3 of 5 dose levels ranging from 1.5-3mg of Ipilimumab and Lenalidomide 10-15 mg. The MTD has not been reached yet. DLT included grade (G) 3 macular rash in 2 patients (dose levels 2 and 3) and G3 pancreatitis (dose level 2). Other G3/4 drug related toxicities included G4 hypopituitarism (n = 1) and G3 pulmonary embolism (n = 1). Of 21 treated patients, 11 (52%) patients had stable disease. The median change in size of target lesions per iRC was 13% (-44% to +86%) with 5 (24%) of patients with at least -10% shrinkage (Hodgkin lymphoma, n = 2; melanoma, n = 1; follicular thyroid carcinoma, n = 1; teratoma, n = 1) lasting for 0.9 to 12.3+ months. The median time-to-treatment failure was 2.1 months (95% CI 1.4-2.8). Conclusion: Ipilimumab and Lenalidomide have manageable side effect profile and demonstrate possible activity in patients with refractory Hodgkin lymphoma, melanoma, follicular thyroid cancer and teratoma. Citation Format: Divya Sakamuri, Sonia L. Betancourt Cuellar, Isabella C. Glitza, Siqing Fu, Jennifer J. Wheler, Gerald S. Falchook, Apostolia M. Tsimberidou, David S. Hong, Vivek Subbiah, Michelle A. Fanale, Maria E. Cabanillas, Funda Meric-Bernstam, Filip Janku. Phase 1 study: Ipilimumab (anti CTLA-4) in combination with Lenalidomide in patients with advanced cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 246. doi:10.1158/1538-7445.AM2015-246
Abstract 15682: Does Gender Still Influence Mortality Post Percutaneous Coronary Intervention (PCI)? A Meta-Analysis of the Impact of Gender on PCI Outcomes
Authors: Ameera Ahmed, Don Pham, Salim Virani, Ihab R Hamzeh, Hani Jneid, Nasser Lakkis, Mahboob Alam
Journal: Circulation (2014)

Objectives:  We examined the effect of gender on mortality and morbidity post PCI.   Background:  Female gender traditionally has been associated with worse overall outcomes post PCI. It is hypothesized that women with CAD tend to be older and have more co-morbid conditions. It is thought that those factors may increase the risk of complications and cardiovascular mortality. However, there is no conclusive evidence whether women have higher mortality and rate of complications in recent times.   Methods:  An extensive literature search using PubMed (MeSH keywords: ‘PCI’ & ‘gender’) identified 31 studies reporting PCI outcomes with gender stratification. We limited our search from 01/01/2000 - 01/31/2014. Thirty one studies were chosen and a total of 707,448 patients (463,053 men, 244,395 women) were included in this analysis. Data on baseline and clinical outcomes were extracted. Clinical outcomes of interest included all-cause mortality, non-fatal MI, stroke and repeat revascularization. Effect size was estimated using Odds Ratio with 95% confidence intervals. Given inherent heterogeneity in reported data, random effects model was used.   Results:  Women tended to have higher mortality than men post PCI:in-hospital mortality 2.7% vs 1.4%, OR 1.69(1.46-1.96), 30-day mortality 18.7% vs 12.2%, OR 1.78(1.46-2.16) and 1 year mortality 13% vs 8.36%, OR 1.49(1.31-1.69). There was no difference in rates of non-fatal MI between men and women [in-hospital MI 1.6% vs 1.4%, OR 1.1(0.92-1.32); 30-day MI 1.94% vs 1.91%, OR 1.02(0.87-1.21) and 1-year MI 10.8% vs 9.64% OR 1.11(0.99-1.25)]. Women also had higher rates of stroke while in-hospital, 0.28% vs. 0.15% OR 1.82(1.22-2.70). The two groups had comparable rates of PCI and CABG at follow-up.   Conclusions:  Women tend to have higher mortality post-PCI at both short and intermediate term follow-up. There is comparable rate of non-fatal MI and repeat revascularization post PCI.
OXI 4503-second generation vascular targeting agent: Histopathologic changes and preclinical efficacy
Authors: Amyn M. Rojiani, Mumtaz V. Rojiani, Dietmar W. Siemann
Journal: Cancer Research (2004)

4103   Vascular targeting agents (VTAs), particularly tubulin-binding agents such as combretastatin A4 disodium phosphate (CA4DP) are currently being examined in various clinical trials. One of the limitations of these agents has been the survival of a rim of neoplastic tissue at the periphery of the tumor. Preclinical investigations in animals have convincingly demonstrated that simply increasing the dose of the VTA does not overcome this problem. More recently, an analog of combretastatin, the lead compound of the A series -OXI 4503 has been evaluated in various animal studies. This compound has been significantly more effective in eliminating or substantially reducing the viable rim of tissue (Hill  et al , 2002). In the present series of experiments we have examined the preclinical efficacy and histopathologic effects of this compound in the rodent KHT and human KSY sarcoma models and Caki-1 human renal cell carcinoma models. Consistent with previous results of Hill  et al  2002, we observed that OXI 4503 was both more potent than combretastatin A4 disodium phosphate (CA4DP) on a per dose basis. For example, compared to CA4DP, 4-fold lower doses of OXI 4503 resulted in equivalent reductions in KHT sarcoma clonogenic cell survival. Perhaps most interestingly, histologic and morphometric assessments carried out using image analysis system on tumor sections showed the viable tissue remaining in these tumors 24 hr after treatment with a 25 mg/kg dose of OXI 4503 to be less than 6%. There was extensive necrosis induced within the tumor. This pattern extended to the very edge of the tumor, stopping at the surrounding soft tissue at many locations; while at other sites there remained a rim that was few cells thick. The induction of necrosis was evident in areas of skeletal muscle infiltrated by tumor, however adjacent uninvolved muscle and soft tissue remained viable. Additionally, treatment with OXI4503 resulted in significant tumor growth delays, a parameter that has shown limited success in CA4DP treated animals. The present findings suggest that OXI4503 bears certain similarities to the parent compound CA4DP. However its increased efficacy both in terms of eliminating/ reducing the peripheral rim of tumor and inducing significant tumor growth delays as well as its increased potency suggest that it may be of greater therapeutic significance. These studies also raise the possibility that in addition to conventional VTA properties, OXI 4503 may exert cytotoxic effects. Additional investigations are currently in progress to further evaluate the  in vitro  and  in vivo  activities of OXI 4503. These experiments should provide further evidence of the potency of the second generation VTA OXI 4503 and its potential for use in single agent therapy.
Primary Prevention of Type 2 Diabetes Mellitus by Lifestyle Intervention: Implications for Health Policy
Authors: David F Williamson, Frank Vinicor, Barbara A Bowman
Journal: Annals of Internal Medicine (2004)

More than 18 million Americans currently have diabetes mellitus. The economic and human cost of the disease is devastating. In the United States, diabetes is the most common cause of blindness among working-age adults, the most common cause of nontraumatic amputations and end-stage renal disease, and the sixth most common cause of death. For the cohort of Americans born in 2000, the estimated lifetime risk for diabetes is more than 1 in 3. In the next 50 years, the number of diagnosed cases of diabetes is predicted to increase by 165% in the United States, with the largest relative increases seen among African Americans, American Indians, Alaska Natives, Asian and Pacific Islanders, and Hispanic/Latino persons. Compelling scientific evidence indicates that lifestyle change prevents or delays the occurrence of type 2 diabetes in high-risk groups. This body of evidence from randomized, controlled trials conducted in 3 countries has definitively established that maintenance of modest weight loss through diet and physical activity reduces the incidence of type 2 diabetes in high-risk persons by about 40% to 60% over 3 to 4 years. The number of persons at high risk for type 2 diabetes is similar to the number of persons who have diabetes. This paper summarizes scientific evidence supporting lifestyle intervention to prevent type 2 diabetes and discusses major policy challenges to broad implementation of lifestyle intervention in the health system. *For a list of the members of the Centers for Disease Control and Prevention Primary Prevention Working Group, see the Appendix.
Abstract 16094: Association of Diurnal Blood Pressure Variation and Nocturnal Hypoxia in Patients With Cardiovascular Risk Factors: Japan Morning Surge-Home Blood Pressure (J-HOP) SAS Study
Authors: Masahisa Shimpo, Satoshi Hoshide, Michiaki Nagai, Kazuo Eguchi, Kazuomi Kario
Journal: Circulation (2014)

Introduction: Abnormal diurnal blood pressure (BP) variation, such as riser or extreme-dipper, is known as risk factors of target organ damage and subsequent cardiovascular events. Nocturnal hypoxia due to sleep apnea syndrome (SAS) is likely to influence diurnal BP variation and risk increase; however, little has been evaluated in large scale cohort in Asian population. Hypothesis: We assessed the hypothesis that diurnal BP variation is associated with nocturnal hypoxia in high risk Japanese patients. Methods: The study subjects were 1087 participants of the J-HOP Study with one or more cardiovascular risk factors (n=4019). Pulse oximetry oxygen saturation (SpO2) was measured with a validated device (PULSOX Me-300; Teijin Pharma, Tokyo, Japan) simultaneously with ambulatory BP monitoring (ABPM). Results: The frequency of each diurnal BP variation are as follows; dipper (normal circadian rhythm) 42.8%, non-dippers 34.6%, extreme-dipper 13.2%, riser 9.4%. When assessed by 3% oxygen desaturation index (ODI; times/h), 14.2% of patients showed 3%ODI≥15 (suspected moderate sleep apnea), and 2.8% of patients showed 3%ODI≥30 (suspected severe sleep apnea). The likelihood of coexisting severe sleep apnea (3%ODI≥30) was significantly higher (5.9%) in patients with riser pattern compared with that in dipper pattern (1.9%) (odd ratio 3.17; 95%CI 1.10-9.11, p&lt;0.03). Three percent ODI was significantly higher in patients with riser pattern than that in dipper pattern (6.6 vs 5.1 times/h; p=0.01). Furthermore, the patients in the longest time spent with SpO2 &lt;90% category in quintiles had an increased likelihood of extreme-dipper pattern compared with those in the shorter categories (odds ratio 1.71; 95%CI 1.10-2.65; p&lt;0.03). Conclusion: Abnormal diurnal BP variation was associated with nocturnal hypoxia in patients with cardiovascular risk factors. For the patients with riser or extreme-dipper pattern, further evaluations are recommended to detect higher risk patients with nocturnal hypoxia, such as SAS, heart failure or chronic pulmonary diseases.