tbuckley/cabot-search huggingface dataset:
Significance of Endothelial Progenitor Cells in Subjects With Diabetes
Authors: Gian Paolo Fadini, Saverio Sartore, Carlo Agostini, Angelo Avogaro
Journal: Diabetes Care (2007)

Diabetes complications represent a huge burden for patients and health services. The fight against each single complication has led to significant improvements in diabetes care, especially for microvascular complications, yet macroangiopathy remains a major source of morbidity and mortality. A common approach for the prevention and treatment of diabetes complications relies on the understanding of their complex pathophysiology. A unifying biochemical theory suggests that oxidative stress underlies subsequent cellular damage pathways, which leads to diabetes complications, but common supracellular mechanisms are still unclear. Endothelial progenitor cells (EPCs) are circulating immature cells that contribute to vascular homeostasis and compensatory angiogenesis. During the last decade, data have become available indicating that alterations in EPCs may have an important causative role in the development and progression of virtually all diabetes complications. In this review, we will focus on the mechanisms of EPC reduction and dysfunction associated with diabetes by discussing their role in each single complication and possible therapeutic interventions.

Diabetes is associated with a unique constellation of disabling complications. While it was originally thought that a single patient tends to develop the cluster of micro- or macrovascular complications, recent prospective studies show that typical markers of microvascular dysfunction, such as microalbuminuria or retinal vascular abnormalities, are associated with an increased risk of macrovascular events (1,2). These and other data suggest that there must be a unifying pathogenetic model underlying diabetes complications. To date, the most credited and supported model proposes that oxidative stress originating from mitochondria activates all subcellular damage pathways (3). However, subsequent events diverge for each complication, and there is not a supracellular unifying hypothesis.

The discovery that a subset of circulating immature cells contributes to vascular homeostasis has been a major achievement in many fields of basic science. In this review, we will focus the attention on …
Renoprotection
Authors: Liffert Vogt, Gerjan Navis, Dick de Zeeuw
Journal: Journal of the American Society of Nephrology (2002)

Data from recent clinical trials show that lowering of BP reduces the rate of renal function loss in chronic renal disease. There is evidence supporting the assertion that BP lowering obtained by intervention in the renin-angiotensin-aldosterone system (RAAS) has an additive renoprotective effect in both diabetic and nondiabetic renal diseases. However, to dissociate BP-dependent and non-BP-dependent action of RAAS blockade, the relevant trials are in many cases flawed by design, resulting in BP differences between the comparative antihypertensive strategies. This review discusses whether the relevant literature allows for the conclusion that RAAS intervention has renoprotective effects in addition to its effects on BP. In particular, the main evidence for a specific renoprotective action of RAAS blockade is provided by its consistent antiproteinuric action, which cannot completely be attributed to the reduction in BP. Indeed, other strategies that lower proteinuria without having an antihypertensive effect, such as lowering dietary protein intake or the use of non-steroidal antiinflammatory drugs, appear to have a renoprotective effect as well. Interestingly, a consistent finding across different intervention studies is that the more proteinuria is reduced the better the kidney appears to be protected. Therefore, it is concluded that agent-characteristics of RAAS intervention (i.e., antiproteinuric properties) independently influence renal function loss in addition to its BP-lowering effect. Future studies should further explore the renoprotective benefit of non-antihypertensive intervention measures, alone and in combination with antihypertensive strategies.
The Use of Psychoactive Drugs in the Outpatient Treatment of Psychiatric Disorders of Children
Authors: IRVIN A. KRAFT
Journal: American Journal of Psychiatry (1968)

Three outpatient treatment patterns involving the use of psychoactive drugs for children are described. In discussing each treatment mode, the author stresses the setting, in which at least three persons interact—the child, a parent, and the physician. He suggests that in this human context of psychopharmacotherapy the essential pharmacological actions of the drug may be either enhanced or diminished.
Nailfold capillary microscopy in healthy children and in childhood rheumatic diseases: a prospective single blind observational study
Authors: P Dolezalova
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objectives:</b> To develop an objective method of nailfold capillaroscopy (NFC), applicable to a wide age range of paediatric patients. To compare the morphological characteristics of the nailfold capillaries in different rheumatology patient groups and controls. <b>Methods:</b> A colour digital video camera attached to a stereomicroscope was used to capture nailfold capillary images. Computerised image processing was used to analyse and store data. Subsequent quantitative and qualitative morphological analysis was performed in the following paediatric patient and control groups: 18 children with connective tissue diseases (CTD: juvenile dermatomyositis, systemic sclerosis, and undifferentiated connective tissue disease), eight with systemic lupus erythematosus, nine with primary Raynaud's disease, three with primary vasculitis, 15 with juvenile idiopathic arthritis, 17 healthy children and 20 healthy adults. Images were analysed by a single assessor who was unaware of the patient details. <b>Results:</b> The NFC technique was simple to perform and gave reproducible results, although some intra- and intersubject variation was noted. Capillary density and width was age related, with younger children having fewer and wider capillaries than older children and adults. Linear capillary density was significantly higher in healthy adults (mean (SD) 8.6 (1.6) capillaries/mm) compared with healthy children (HC 6.9 (0.9) capillaries/mm). The group with CTD had the most abnormal findings, with lower linear density (4.9 (1.7) capillaries/mm) and increased capillary loop width (10.7 (7.3) mm) compared with HC (3.5 (1.7) mm). In addition, 11/18 (61%) patients in the CTD group had more than two definitely abnormal capillaries in at least two nailfolds, an abnormality not seen in other subjects. Two qualitative measures, the degree of avascularity and general disarrangement of capillary pattern, were more commonly observed in the CTD group than in HC. The proportion of tortuous capillaries did not differ significantly between study groups. <b>Conclusions:</b> This study is unique in measuring objective quantitative and qualitative parameters of the nailfold vasculature across a wide spectrum of age and disease. Differences in capillary morphology and frequency in children with CTD compared with other paediatric diseases and healthy controls were demonstrated. In the clinical situation, an assessment of the general degree of disarrangement may offer a fast tool for assessment of the nailfold vasculature which correlates well with NFC data.
Extensive genomic diversity and selective conservation of virulence-determinants in enterohemorrhagic Escherichia coli strains of O157 and non-O157 serotypes
Authors: Yoshitoshi Ogura, Tadasuke Ooka, None Asadulghani, Jun Terajima, Jean-Philippe Nougayrède, Ken Kurokawa, Kousuke Tashiro, Toru Tobe, Keisuke Nakayama, Satoru Kuhara, Eric Oswald, Haruo Watanabe, Tetsuya Hayashi
Journal: Genome biology (2007)

Abstract Background Enterohemorrhagic Escherichia coli (EHEC) O157 causes severe food-borne illness in humans. The chromosome of O157 consists of 4.1 Mb backbone sequences shared by benign E. coli K-12, and 1.4 Mb O157-specific sequences encoding many virulence determinants, such as Shiga toxin genes ( stx genes) and the locus of enterocyte effacement (LEE). Non-O157 EHECs belonging to distinct clonal lineages from O157 also cause similar illness in humans. According to the 'parallel' evolution model, they have independently acquired the major virulence determinants, the stx genes and LEE. However, the genomic differences between O157 and non-O157 EHECs have not yet been systematically analyzed. Results Using microarray and whole genome PCR scanning analyses, we performed a whole genome comparison of 20 EHEC strains of O26, O111, and O103 serotypes with O157. In non-O157 EHEC strains, although genome sizes were similar with or rather larger than O157 and the backbone regions were well conserved, O157-specific regions were very poorly conserved. Around only 20% of the O157-specific genes were fully conserved in each non-O157 serotype. However, the non-O157 EHECs contained a significant number of virulence genes that are found on prophages and plasmids in O157, and also multiple prophages similar to, but significantly divergent from, those in O157. Conclusion Although O157 and non-O157 EHECs have independently acquired a huge amount of serotype- or strain-specific genes by lateral gene transfer, they share an unexpectedly large number of virulence genes. Independent infections of similar but distinct bacteriophages carrying these virulence determinants are deeply involved in the evolution of O157 and non-O157 EHECs.
A community survey of respiratory disease among East Indian and African adults in Guyana
Authors: G. J. Miller, M. T. Ashcroft
Journal: Thorax (1971)

The belief that chronic bronchitis is more prevalent among Indians than Africans in the Caribbean area was investigated by a community survey in Guyana. Respiratory symptoms were assessed by a standard questionnaire, ventilatory capacities were measured, and chest radiographs were taken of some 800 African and Indian men and women aged 35 to 54 years living in adjacent and similar communities. Histories of morning cough, chronic cough, morning phlegm, and chronic phlegm (chronic bronchitis) were more common in Indians than Africans. Although these respiratory symptoms were much more common in smokers than non-smokers, the higher prevalence rates in Indians could not be explained by smoking habits which were similar in the two races. Chronic bronchitis occurred in 17·3% of Indian and 2·4% of African male smokers and in 16·1% and 2·2% of Indian and African female non-smokers respectively. Judging by the history, lung function, and clinical signs, chronic bronchitis was more severe in Indians than Africans. The condition was more common among field labourers on sugar estates but, although the majority of field labourers were Indian, this occupational difference only partially explained the difference in prevalence between Indians and Africans. Indians, for reasons unknown, appear to have a greater susceptibility than Africans to chronic bronchitis.
Increased risk of inflammatory bowel disease in women with endometriosis: a nationwide Danish cohort study
Authors: Tine Jess, Morten Frisch, Kristian Tore Jørgensen, Bo Vestergaard Pedersen, Nete Munk Nielsen
Journal: Gut (2011)

<h3>Background</h3> An association between endometriosis and certain autoimmune diseases has been suggested. However, the impact of endometriosis on risk of inflammatory bowel disease (IBD) remains unknown. <h3>Objective</h3> To assess the risk of Crohn9s disease (CD) and ulcerative colitis (UC) in an unselected nationwide Danish cohort of women with endometriosis. <h3>Design</h3> By use of national registers, 37 661 women hospitalised with endometriosis during 1977–2007 were identified. The relative risk of developing IBD after an endometriosis diagnosis was calculated as observed versus expected numbers and presented as standardised incidence ratios (SIRs) with 95% CIs. <h3>Results</h3> Women with endometriosis had a increased risk of IBD overall (SIR=1.5; 95% CI 1.4 to 1.7) and of UC (SIR=1.5; 95% CI 1.3 to 1.7) and CD (SIR=1.6; 95% CI 1.3 to 2.0) separately, even 20 years after a diagnosis of endometriosis (UC: SIR=1.5; 95% CI 1.1 to 2.1; CD: SIR=1.8; 95% CI 1.1 to 3.2). Restricting analyses to women with surgically verified endometriosis suggested even stronger associations (UC: SIR=1.8; 95% CI 1.4 to 2.3; CD: SIR=1.7; 95% CI 1.2 to 2.5). <h3>Conclusion</h3> The risk of IBD in women with endometriosis was increased even in the long term, hence suggesting a genuine association between the diseases, which may either reflect common immunological features or an impact of endometriosis treatment with oral contraceptives on risk of IBD.
Premature ovarian failure: a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy
Authors: Y. van Kasteren
Journal: Human Reproduction Update (1999)

Infertility is an important issue for patients with premature ovarian failure (POF). Although oocyte donation offers an alternative method to achieve a pregnancy, many patients seek to reproduce with their own gametes. We performed a literature search to evaluate the possibility of pregnancy following diagnosis, and the additional value of treatment strategies. We found 52 case reports, eight observational studies, nine uncontrolled studies and seven controlled trials. Due to a strong variability in study design, patient selection and mode of intervention, it was not possible to combine the data of the seven studies to perform a meta-analysis. None of the studies showed a statistically significant difference between both (or more) study groups. Due to a lack of incorporation of a placebo group, preference of any treatment over no treatment could not be established. Importantly, the collected data of observational, uncontrolled and controlled studies indicate that POF patients still have a 5-10% chance to conceive following diagnosis. Approximately 80% of the reported pregnancies resulted in the birth of a healthy child. There is no evidence that any treatment can enhance this pregnancy rate.
Vaccine could give protection against cervical cancer
Authors: S. Gottlieb
Journal: BMJ (2002)

Researchers have developed an experimental vaccine that seems to give women complete protection against a virus that causes most cases of cervical cancer.

The vaccine will not be available to women for several years, as researchers continue work to ensure that the vaccine can deliver long term blanket protection against the sexually transmitted human papillomavirus (HPV), believed to be responsible for most cases of cervical cancer. But the new study proves a long debated point: viruses that cause cancer can …
Sunitinib Reverses Type-1 Immune Suppression and Decreases T-Regulatory Cells in Renal Cell Carcinoma Patients
Authors: James H. Finke, Brian Rini, Joanna Ireland, Patricia Rayman, Amy Richmond, Ali Golshayan, Laura Wood, Paul Elson, Jorge Garcia, Robert Dreicer, Ronald Bukowski
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Immune dysfunction is well documented in renal cell carcinoma (RCC) patients and likely contributes to tumor evasion. This dysfunction includes a shift from a type-1 to a type-2 T-cell cytokine response and enhanced T-regulatory (Treg) cell expression. Given the antitumor activity of select tyrosine kinase inhibitors such as sunitinib in metastatic RCC (mRCC) patients, it is relevant to assess their effect on the immune system. Experimental Design: Type-1 (IFNγ) and type-2 (interleukin-4) responses were assessed in T cells at baseline and day 28 of treatment with sunitinib (50 mg/d) by measuring intracellular cytokines after in vitro stimulation with anti-CD3/anti-CD28 antibodies. Results: After one cycle of treatment, there was a significant increase in the percentage of IFNγ-producing T cells (CD3+, P &amp;lt; 0.001; CD3+CD4+, P = 0.001), a reduction in interleukin-4 production (CD3+ cells, P = 0.05), and a diminished type-2 bias (P = 0.005). The increase in type-1 response may be partly related to modulation of Treg cells. The increased percentage of Treg cells noted in mRCC patients over healthy donors (P = 0.001) was reduced after treatment, although not reaching statistical significance. There was, however, an inverse correlation between the increase in type-1 response after two cycles of treatment and a decrease in the percentage of Treg cells (r = −0.64, P = 0.01). In vitro studies suggest that the effects of sunitinib on Treg cells are indirect. Conclusions: The demonstration that sunitinib improved type-1 T-cell cytokine response in mRCC patients while reducing Treg function provides a basis for the rational combination of sunitinib and immunotherapy in mRCC.
Treatment-Resistant Depression and Mortality After Acute Coronary Syndrome
Authors: Robert M. Carney, Kenneth E. Freedland
Journal: American Journal of Psychiatry (2009)

Depression is a risk factor for morbidity and mortality in patients with coronary heart disease, especially following acute coronary syndrome. Evidence from recent clinical trials suggests that treatment-resistant depression may be associated with a particularly high risk of mortality or cardiac morbidity in patients following acute coronary syndrome. This article reviews this evidence and considers possible explanations for this relationship. Directions for future research are also considered, with particular emphasis on efforts to elucidate the underlying mechanisms and to develop more efficacious treatments for depression in patients with coronary heart disease.
British Association of Dermatologists guidelines for use of biological interventions in psoriasis 2005
Authors: C.H. Smith, A.V. Anstey, J.N.W.N. Barker, A.D. Burden, R.J.G. Chalmers, D. Chandler, A.Y. Finlay, C.E.M. Grifitths, K. Jackson, N.J. McHugh, K.E. McKenna, N.J. Reynolds, A.D. Ormerod
Journal: British Journal of Dermatology (2005)
Psoriatic arthritis therapy: NSAIDs and traditional DMARDs
Authors: P Nash, D O Clegg
Journal: Annals of the Rheumatic Diseases (2005)

Non-steroidal anti-inflammatory drugs (NSAIDs) and traditional disease modifying antirheumatic drugs (DMARDs) are widely used in the treatment of psoriatic arthritis (PsA), but this is based more upon clinical experience than adequate evidence from clinical trials. This report summarises the results from available trials highlighting evidence of efficacy and deficiencies with respect to effect on joints and to a lesser degree cutaneous disease. The available published data on efficacy of NSAIDs, glucocorticoids, antimalarials, sulfasalazine, gold, methotrexate, azathioprine, and ciclosporin are detailed, as well as new data on leflunomide and other novel agents. The conclusions of this review are that evidence supports marginal efficacy of sulfasalazine and perhaps gold in the treatment of peripheral psoriatic arthropathy, and methotrexate and ciclosporin are effective for treating the skin disease although evidence for improvement of the arthropathy is empirical at best. New trials with standardised and validated outcome measures are required to better assess efficacy. Evaluating newer agents, against and in combination with traditional DMARDS, may further clarify the latter's role in the future management of this condition.
Pathology Review of Thin Melanoma and Melanoma in Situ in a Multidisciplinary Melanoma Clinic: Impact on Treatment Decisions
Authors: Alfredo A. Santillan, Jane L. Messina, Suroosh S. Marzban, Gema Crespo, Vernon K. Sondak, Jonathan S. Zager
Journal: Journal of Clinical Oncology (2009)

Patients with thin melanoma (<or= 1.0 mm) and melanoma in situ (MIS) represent the majority of newly diagnosed melanoma. We estimated the impact of expert review of outside pathology material on the staging and thus treatment decisions affecting patients referred to a multidisciplinary clinic with early-stage melanoma.We studied patients with a diagnosis of thin melanoma or MIS referred to H. Lee Moffitt Cancer Center from 2006 to 2009. After comparing the referring laboratory and in-house dermatopathologic interpretations, we calculated any differences in diagnosis and tumor staging and the potential impact of differences in diagnosis and staging on prognosis and surgical treatment using the National Comprehensive Cancer Network clinical guidelines.The overall pathologic discordance rate in diagnosis was 4% (15 of 420 patients; 95% CI, 2% to 6%). The overall change in tumor staging rate was 24% (97 of 405 patients; 95% CI, 20% to 28%). Pathology review led to changes in surgical excision margins in 12% of patients (52 of 420 patients; 95% CI, 9% to 16%) and in the decision about whether to perform a sentinel lymph node biopsy in 16% of patients (67 of 420 patients; 95% CI, 13% to 20%). Key pathologic factors, particularly mitotic rate, were frequently missing from outside pathology reports.Our data suggest that review of thin melanoma or MIS by an expert dermatopathologist results in frequent, clinically meaningful alterations in diagnosis, staging, prognosis, and surgical treatment. Referral of these patients to a multidisciplinary melanoma clinic is appropriate, and management of such patients should include review of the biopsy whenever feasible.
Estimation of Total Glomerular Number in Stable Renal Transplants
Authors: Xavier Fulladosa, Francesc Moreso, Jose A Narváez, Josep M Grinyó, Daniel Serón
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Glomerular number (Ng) is considered a major determinant of renal function and outcome. In the dog, it has been shown that Ng can be estimated with reasonable precision in vivo by means of a renal biopsy and magnetic resonance imaging (MRI). Thus, this method was applied to study anatomoclinical correlations in stable human renal transplants. Thirty-nine stable renal transplants were included. A protocol renal allograft biopsy was done at 4 mo. Biopsies were evaluated according to Banff criteria. Glomerular volume fraction (Vvglom/cortex) was measured by means of a point-counting method, and mean glomerular volume (Vg) was estimated by means of Weibel and Gomez (Vg-W&G) and maximal profile area (Vg-MPA) methods. MRI was used to estimate renal cortical volume (Vcortex). Ng was calculated as (Vvglom/cortex × Vcortex)/Vg. GFR was estimated by the inulin clearance. Ten age-matched donor biopsies served as controls for Vg. Histologic diagnosis was as follows: normal (n = 20), borderline (n = 7), acute rejection (n = 1), and chronic allograft nephropathy (n = 11). Vvglom/cortex was 3.4 ± 1.1%, Vcortex was 167 ± 46 cm3, Vg-W&G was 3.2 ± 1.2 × 106 μm3, and Vg-MPA was 3.3 ± 1.0 × 106 μm3. Vg-W&G in donor and recipient biopsies was not different (3.6 ± 1.1 versus 3.2 ± 1.2 × 106 μm3). Total glomerular number estimated by means of Vg-W&G (Ng-W&G) was 0.73 ± 0.33 × 106 and by Vg-MPA (Ng-MPA) was 0.74 ± 0.31 × 106. A positive correlation between GFR and Ng-W&G (r = 0.47, P = 0.002) was observed. Furthermore, the older the donor, the higher Vg-W&G (r = 0.37, P = 0.01) and the lower Ng-W&G (r = −0.40, P = 0.01). Total glomerular number can be estimated in stable renal allografts by means of a renal biopsy and MRI. Our data show that Ng depends on donor age and positively correlates with GFR. E-mail: [email protected]