Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of tacrine on regional cerebral blood flow in Alzheimer's disease

Regional cerebral blood flow (rCBF) was studied in nine patients with Alzheimer's disease before and after treatment with tacrine. A small but significant improvement in cognitive functioning on the drug was not accompanied by significant changes in rCBF for the group as a whole. However, when the analysis was repeated excluding the only patient who showed no clinical response to the drug a significant increase in rCBF was seen to the right posterior temporal area. This preliminary study shows that some caution is necessary when interpreting studies of rCBF as changes in cognitive functioning may not always be accompanied by parallel changes in rCBF. Separate analysis of drug responders and non‐responders may be a fruitful area for further research.
Lymphocyte populations and apoptosis of peripheral blood B and T lymphocytes in children with end stage renal disease

Abstract Background: End stage renal disease (ESRD) is a worldwide devastating health problem due to its increased prevalence in the population and high association with several pathologic conditions including immunodeficiency, which makes a significant contribution to morbidity and mortality. Aim: The present study aimed at analysis of T and B lymphocyte subpopulation and the detection of flowcytometric apoptosis markers on peripheral B and T lymphocytes in a cohort of children with ESRD. Subjects and methods: A case–control study was conducted on 28 children with ESRD. In addition, 30 age and sex matched healthy children were included as a control group. We used Annexin V-FITC binding assay as a sensitive probe for identifying cells undergoing apoptosis. Results: Circulating neutrophils, T and B lymphocytes were lower in patient group. In addition, apoptotic B and T lymphocytes occurred more frequently in children with ESRD than in the control group. Conclusion: Our finding of low numbers of circulating neutrophils, T and B lymphocytes, and increased portion of apoptotic B and T lymphocytes in children with ESRD, may emphasize the fact that these derangements are the main mechanisms responsible for the impairment of the immune system in ESRD children, also it adds to the fact that both cellular and humoral immunity affected in ESRD children. Finally, uremia and increased peripheral lymphocyte apoptosis were the major causes of lymphocyte populations' depletion in our ESRD patients.
SIDS, illness, and acute medical care

One component of the Back to Sleep campaign to reduce the risk of sudden infant death syndrome (SIDS) is the recommendation that parents seek medical attention if their infant is unwell. The aim of this study was to investigate if SIDS could in part be explained by sick infants not getting appropriate medical care. Data on symptoms of illness and on acute medical contacts made for infants dying from SIDS (n = 390) within two weeks of their death were compared with those from a randomly selected group of control infants (n = 1592). SIDS cases had more severe illness than controls (odds ratio (OR) = 3.43; 95% confidence interval (CI)= 1.69 to 5.38), and were more likely to have seen a general practitioner (OR = 1.37; 95% CI = 1.09 to 1.73) or attended hospital (OR = 3.43, 95% CI = 1.09 to 1.73). Only 1.3% of all SIDS cases had symptoms suggesting severe illness and had not seen a general practitioner. A lack of medical contacts in the two weeks before death does not contribute to the risk of SIDS.
Fractures of the occipital condyle clinical spectrum and course in eight patients

Introduction: Occipital condyle fractures (OCFs) are considered to be rare injuries. OCFs are now diagnosed more often because of the widespread use of computed tomography. Our aim is to report the incidence, treatment and long term outcome of 8 patients with OCFs. Materials and Methods: All patients presenting with multiple trauma from 1993 to 2006 were analyzed retrospectively. Characteristics and course of the treatment were evaluated. Follow-up was performed after 11,7 years (range 5,9 to 19,3 years). Results: Nine cases of OCF in 8 patients were identified. All injuries resulted from high velocity trauma. The average scores on the ISS Scale were 39,6 (24-75) and 7,3 (3-15) on the GCS. According to Anderson's classification, 5 cases of Type III and 4 cases of Type I fractures were identified. According to Tuli's classification, 5 cases of Type IIA and 4 cases of Type I were found. Indications for immobilization with the halo-vest were type III injuries according to Anderson's classification or Tuli's type IIA injuries, respectively. Patients with Tuli's type I injuries were treated with a Philadelphia collar for 6 weeks. In one patient with initial complete tetraplegia and one with incomplete neurological deficits the final follow-up neurologic examination showed no neurological impairment at all (Frankel-grade A to E, respectively B to E). At follow-up, 3 patients were asymptomatic. Four patients suffered from mild pain when turning their head, pain medication was necessary in one case only. Discussion: OCF's are virtually undetectable using conventional radiography. In cases of high velocity, cranio-cervical trauma or impaired consciousness, high resolution CT-scans of the craniocervical junction must be performed. We suggest immobilization using a halo device for type III injuries according to Anderson's classification or Tuli's type IIa injuries, respectively. Patients with Tuli's type I injuries should be treated with a Philadelphia collar.
Assessment of dentition status and treatment needs of police personnel in Bhopal city, Central India -

Background: Oral health is an integral part of general health. Police personnel form the backbone for safety and security of a community hence their health is of utmost importance. Objectives: To assess the dentition status of police personnel in Bhopal city. Materials and Methods: A cross-sectional study was conducted on 781 subjects (mean aged 40.5 years) who were selected by a simple random sampling method. Type III examination of the subjects was conducted, and along with a questionnaire, decayed, missing, and filled teeth data were recorded on modified WHO format 1997. p-Value ≤0.05 was considered statistically significant. Results: The number of decayed, missing, and filled teeth was significantly lower among this group. Conclusion: The overall caries experience was low in this group. Most of the police personnel lack oral health awareness. Awareness should be created to maintain good oral hygiene.
Update on role of direct renin inhibitor in diabetic kidney disease

Abstract Background: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renin–angiotensin–aldosterone system (RAAS) plays a critical role in the development of DKD with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) being the mainstay of treatment. Systemic RAAS activity has been implicated in the pathogenesis of DKD, but lately interest has shifted to intrarenal RAAS effect. With the discovery of the (pro)renin receptor and ACE independent pathways of angiotensin II production, our understanding of role of renin in end organ damage has improved significantly. Summary: We summarize our current understanding of ACE dependent and independent pathways in the development of DKD and the preclinical models demonstrating renal effects of direct renin inhibitors (DRIs). We then review clinical studies and trials performed so far evaluating the efficacy of aliskiren on renal outcomes and safety in DKD. Key message: At present, there is little evidence for renal benefit of aliskiren in DKD beyond that offered by ACEIs or ARBs. Combining aliskiren with ACEI or ARB in DKD did not significantly improve renal outcomes in comparison with ACEI or ARB monotherapy in clinical trials. Slightly more adverse events including hyperkalemia, acute kidney injury and hypotension were observed in the combination therapy as compared to the monotherapy. Thus, current evidence suggests that aliskiren, because of its antihypertensive and antiproteinuric effects, maybe used as monotherapy in DKD and considered an equivalent alternative to ACEIs or ARBs. Careful monitoring for renal adverse effects would allow safe clinical use of DRI.
More on the “Triple Whammy”: antihypertensive drugs, non-steroidal anti-inflammatory agents and acute kidney injury – a case/non-case study in the French pharmacovigilance database

Abstract It has been suggested that the risk of acute kidney injury (AKI) increases with the number of drugs associated between non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme inhibitors (ACEis) [or angiotensin receptor blockers (ARBs)] and diuretics. We aimed to investigate whether the number of drugs associated between NSAIDs, ACEis, ARBs and diuretics was associated to disproportionate reporting of AKI in the French Pharmacovigilance Database. In reports of Adverse Drug Reactions (ADRs) recorded between 01 January 2008 and 31 December 2010, we selected patients whose medications included at least one oral antihypertensive drug. We used a case/non-case methodology. Cases were AKI and non-cases were all the remaining reports. Among the 11,442 ADR reports in patients under antihypertensive drug recorded in the French Pharmacovigilance Database, 837 ADRs were AKI (7.3%, 95% CI 6.8–7.8). AKI and the number of drugs associated were disproportionately reported (one drug alone: adjusted ROR 2.19, 95% CI: 1.65–2.89, two drugs: adjusted ROR 5.27, 95% CI: 4.00–6.94, three and more: adjusted ROR 16.46, 95% CI: 11.38–23.80). There was no significant association between NSAIDs’ half-lives and reporting of AKI (adjusted ROR = 0.54, 95% CI: 0.25–1.15). Given the widespread use of these hazardous drugs in general population, caution is needed when they are associated.
New information about the polymyxin/colistin class of antibiotics

Infections by multidrug resistant Gram-negative bacilli (MDR-GNB) have become a major threat for patients hospitalized in intensive care units, representing a prevalent cause of morbimortality in the critically ill, since these microorganisms have developed resistance to most available antimicrobial agents. In this respect, very few therapeutic innovations have been developed in recent years, and it is not foreseen that any new drugs will be commercialized in the near future. Tigecycline represents an effective alternative in this setting, but lacks activity against Pseudomonas aeruginosa, and its use has not been validated for all organ-specific infections. Frequently, only old antibiotics like colistin remain a valid option. New pharmaceutical formulations and dosage regimens of polymyxins have considerably reduced the toxicity previously attributed to these antimicrobials, and have made it possible to reintroduce them into clinical practice. Nonetheless, the effectiveness of polymyxins is still suboptimal, and the expansion of heteroresistance and pan-drug-resistant strains of gram-negative bacilli is of concern. Improvements in dosing, alternative methods of administration and different synergic antimicrobial combinations have been proposed in recent literature, among other measures, to enhance the effectiveness of polymyxins. The latest data regarding polymyxins and their clinical use are discussed in this review.
Reduction of blood pressure in patients with treatment-resistant hypertension

Background: Resistant hypertension is a common clinical problem, and patients with resistant hypertension have increased cardiovascular risk. It is a subset of the hypertensive population that is little studied and poorly characterized. Objective: The purpose of this review is to discuss resistant hypertension, its recognition and diagnostic workup and management, and to present current data about the disease from the latest research. Methods: We define resistant hypertension and differentiate it from pseudoresistance. We identify diagnostic tests that may be done on patients with resistant hypertension. Last, we discuss therapeutic approaches to resistant hypertension, focusing on pharmacological treatment, and present an algorithm that may be used by the clinician in treating a patient with resistant hypertension. Conclusion: Resistant hypertension is a significant clinical problem commonly encountered by clinicians. Patients with resistant hypertension have increased cardiovascular risk. In evaluating for resistant hypertension, it is important to recognize elements that contribute to pseudoresistance to treatment. Secondary causes of hypertension are common in patients with resistant hypertension and should be included in the diagnostic workup. Pharmacological treatment for resistant hypertension entails choosing medications with complementary mechanisms of action, optimizing diuretic use, and considering the use of mineralocorticoid antagonists as an add-on agent to the antihypertensive regimen.
Analysis of bone metastasis in head and neck squamous cell carcinoma: Experience of a regional cancer center

Background: Bone metastasis is a rare occurrence in head and neck squamous cell carcinoma (HNSCC). This retrospective study was performed to analyze the frequency and patterns of skeletal metastasis in HNSCC. Materials and Methods : We analyzed records of 8326 HNSCC patients attending our oncology outpatient department from January 2000 to December 2013. All statistical calculations were performed using MedCalc software for windows, version 12.5. 0 (Osterd, Belgium). Results : Bone metastasis was found in 25 patients (0.3% of total HNSCC patients, nasopharynx excluded). 10 patients (0.66%) of carcinoma tonsil had skeletal metastasis. The patients of younger age groups had higher frequency of bone metastasis; 1.56% patients of age group 20-29 years while 0.26% patients of 60-69 years age group had skeletal metastasis (P < 0.001). However, no patient of >70 years age was found to have bone metastasis. Most common site of metastasis was spine (56%) followed by pelvis (32%). Isolated involvement of a single bony site was present in 64% of the metastatic cases. Conclusion: Bone metastasis though very rare, should be considered for evaluation in patients of HNSCC especially in younger patients.
A consensus approach is helpful in gathering disparate evidence, and expert opinion to informational guidance for staff responsible for care after death (last offices)

Background Despite 500,000 deaths p.a. in England and Wales, the National Nurse Consultant Group (Palliative Care), National End of life Programme and Department of Health identified inconsistencies and disagreement about the care of the adult who has died. Aim To produce nationally, multi-professionally agreed guidance, that (A) was sensitive to roles/responsibilities of health/social care professionals (B) offered clarity ensuring consistency of care and appropriate training. Methodology Using a consensus approach, four rounds of decision making occurred (Jones et al 1995). The National Nurse Consultant Group (Palliative Care) provided advice on the only clinical benchmark The Royal Marsden Guidelines (Dougherty and Lister 2008) (round one). The guidelines and advice were broken into statements. Fifty national stakeholder organisations were invited to comment, provide evidence or identify aspects of care not covered. Thirty-five organisations responded. Statements were amended where there was consensus or legal guidance (round two). The second round demonstrated areas of little evidence or consensus for example, containing leakage, identification, or preparation of the deceased. A national stakeholder event discussed these issues (third round of consensus) and outcomes were incorporated and re-circulated (round four of consensus). Over one hundred individuals representing national organisations took part in ‘Guidance for staff responsible for care after death (last offices)’, issued in April 2011, with the endorsement of the Royal College of Nursing and the Royal College of Pathologists. Feedback is that the guidance is welcomed and well received. Conclusion Consensus methodology is helpful and systematic in developing national guidance when the evidence base is disparate and poor, as it draws together professionals enabling debate of clinical knowledge (as source of evidence) and illuminates benchmarks for clinical quality.
Transforming Growth Factor-α—Pseudomonas Exotoxin Fusion Protein (TGF-α-PE38) Treatment of Subcutaneous and Intracranial Human Glioma and Medulloblastoma Xenografts in Athymic Mice

Epidermal growth factor receptor (EGFR) is amplified or overexpressed in many malignant gliomas and other primary brain tumors but is low or undetectable in normal brain. In the present study, this differential expression has been exploited for targeted brain tumor therapy using a TGF-alpha-Pseudomonas exotoxin recombinant toxin, TGF-alpha-PE38. In vitro experiments demonstrate that the cytotoxicity of this fusion protein is primarily determined by tumor EGFR expression and that TGF-alpha-PE38 cytotoxicity is abolished by pretreatment with excess epidermal growth factor. Treatment with i.p. TGF-alpha-PE38 in nude mice bearing glioblastoma or medulloblastoma s.c. xenografts produced tumor regression and growth delay. For intracranial xenograft implants treated with i.p. TGF-alpha-PE38, significant increases in median survival were noted only for tumors with the highest EGFR expression. However, intracranial tumors treated with a single intratumoral injection of TGF-alpha-PE38 showed increased survival in all xenografts tested. These results indicate that TGF-alpha-PE38 is active against primary human brain tumors ranging from moderate to high EGFR expression. For intracranial tumors, however, the higher survival rates produced by intracranial injection of TGF-alpha-PE38 than by continuous i.p. administration suggest that increased drug clearance or impaired drug delivery reduces the efficacy of systemic TGF-alpha-PE38. Direct delivery of TGF-alpha-PE38 into brain tumors by controlled-release biodegradable polymers or intratumoral implanted catheters, or intrathecal administration into the colony stimulating factor of patients with leptomeningeal metastasis, may represent clinically useful applications of recombinant toxin therapy in tumors with high EGFR expression.
Açai berry extract attenuates glycerol-induced acute renal failure in rats

Abstract Acute renal failure (ARF) is one of the most common problems encountered in hospitalized critically ill patients. In recent years great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of ARF. Hence, the current study was designed to investigate the effect of Açai berry extract (ABE) on glycerol-induced ARF in rats. Results of the present study showed that rat groups that received oral ABE in a dose of 100 and 200 mg/kg/day for 7 days before or 7 days after induction of ARF by a single intramuscular glycerol injection reported a significant improvement in kidney functions tests [decrease in serum urea, serum creatinine, and blood urea nitrogen (BUN)] when compared to the ARF model groups. Moreover, there was significant amelioration in renal oxidative stress markers [renal catalase (CAT), renal reduced glutathione (GSH)] and renal histopathological changes in the ABE-treated groups when compared to ARF model groups. The most significant improvement was reported in the groups where ABE was administered in a dose 200 mg/kg/day. These results indicate that ABE has a potential role in ameliorating renal damage involved in ARF.
Protective effect of baicalein on renal ischemia/reperfusion injury in the rat

Abstract Objective: To investigate the protective effect and the mechanism of baicalein (Bai) in rats with renal ischemia–reperfusion injury (RIRI). Methods: Twenty-four male Sprague–Dawley rats were divided into three groups: sham, IR, and IR + Bai. Bai was administered by tail vein injection (30 mg/kg) 30 min before reperfusion in the IR + Bai group. The IR group and sham group received saline vehicle via the intravenous route. Results: Rats that underwent RIRI exhibited renal functional impairment, histological changes, significantly increased advanced oxidation protein product (AOPP) and malondialdehyde (MDA) levels (p < 0.01), and ICAM-1 and MCP-1 protein and mRNA expression were significantly upregulated (p < 0.01). Administration of Bai reduced AOPP and MDA levels, significantly inhibited expression of inflammatory factors (p < 0.05), and markedly improved renal function. Conclusion: Bai promotes the recovery of renal function in established acute RIRI, and alleviates kidney injury in a rat model.
Effects of Sulfasalazine Treatment in Juvenile Idiopathic Arthritis: Clinical and Radiological Observations

In Nederland heeft ongeveer een op de duizend kinderen jeugdreuma. De ziekte kenmerkt zich door chronische gewrichtsontstekingen die kunnen leiden tot blijvende gewrichtsschade. Onderzoeken naar de behandeling en de effecten hiervan op de lange termijn zijn beperkt. Het proefschrift van Marion van Rossum beschrijft een landelijk onderzoek naar de korte- en langetermijnuitkomst van kinderen met jeugdreuma die deelnamen aan een placebo gecontroleerde studie naar de werkzaamheid van het antireumaticum sulfasalazine. De resultaten van de studie laten zien dat sulfasalazine effectiever is dan een placebo in het onderdrukken van gewrichtsontstekingen en het vertragen van radiologisch zichtbare gewrichtsschade. Om de radiologische bevindingen te beschrijven werd een gestandaardiseerde radiologische scoringsmethode ontwikkeld. Deze is gevalideerd en geschikt voor studies bij kinderen met jeugdreuma. De studie naar de langetermijnuitkomst toont dat er nog veel te winnen valt in de behandeling van jeugdreuma. Bij een vervolgstudie die negen jaar na aanvang van de sulfasalazine-studie werd uitgevoerd, werd 90% van de oorspronkelijk deelnemers opnieuw onderzocht (leeftijd 18-25 jaar). 74% van de patienten had nog steeds ontstoken gewrichten. Aanvullende analyses laten zien dat patienten die op jonge leeftijd met sulfasalazine waren behandeld ook op latere leeftijd betere ziekte-uitkomstscores hadden dan de oorspronkelijke placebogroep. Bovendien maakten ze in de tussenliggende periode minder gewrichtsontstekingen door en hadden ze een minder intensieve anti-reumatische behandeling nodig. De vervolgstudie laat ook zien dat patienten met een goede therapietrouw een betere ziekte-uitkomst op de lange termijn hebben. Deze bevindingen ondersteunen het belang van vroegtijdig starten van effectieve anti-reumatische behandeling en een goede therapietrouw bij jeugdreuma.
Loss of matrix metalloproteinase-8 is associated with worsened recovery after ischemic kidney injury

Abstract Acute kidney injury (AKI) leads to chronic kidney disease. The mechanisms involved with recovery from AKI are poorly understood and molecular mediators responsible for healing and restoration of kidney function are understudied. We previously discovered differential expression of matrix metalloproteinase-8 (MMP-8) mRNA and protein in patients with severe sepsis associated AKI versus sepsis without AKI. Here, we demonstrate the involvement of MMP-8 in purely ischemic AKI. Mice subjected to 30 min of bilateral renal ischemia developed increased plasma creatinine and MMP-8 expression within 24 h versus sham controls. After an initial surge and subsequent return toward baseline, both kidney MMP-8 expression and activity exhibited a late increase (Days 5–7 post-ischemia reperfusion) in mice subjected to AKI. Neutrophil infiltration of the kidney was significantly higher after AKI in wild-type mice than in MMP-8 null mice, starting at 4 days. Additionally, MMP-8 null mice subjected to AKI demonstrated a persistent histopathologic and functional injury and worsened health (greater overall weight loss) versus wild-type cohorts after seven days. Taken together, our findings suggest that MMP-8 is involved with restoration of baseline kidney health after ischemic kidney injury and that a potential mechanism involves the interaction of MMP-8 and neutrophil recruitment to the site of injury.