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PubMed1998

Androgen therapy in chronic renal failure.

Chronic renal failure, dialysis and transplantation have major effects on male reproductive health because of the impairment of spermatogenesis, steroidogenesis and sexual function. Hypothalamo-pituitary testicular dysfunction in uraemia is manifest clinically as delayed growth and puberty, sexual dysfunction, androgen deficiency, impaired spermatogenesis and infertility. Apart from renal anaemia, there are at present no proven indications for androgen therapy in chronic renal failure. This chapter reviews the basis and scope for various clinical applications of gonadotropin and androgen therapy as an adjunct to the standard medical care of chronic renal failure. The therapeutic possibilities implied by experimental and clinical findings suggesting that uraemic hypogonadism may be a functional state of gonadotropin deficiency are emphasized.

Anemia↗

PubMed2003

Guided tissue regeneration for the treatment of periodontal intrabony and furcation defects. A systematic review.

BACKGROUND: Many clinical studies have demonstrated that guided tissue regeneration (GTR) is a successful treatment modality of periodontal reconstructive surgery and it has become an accepted procedure in most periodontal practices. RATIONALE: The purpose of this structured review was to assess the efficacy of guided tissue regeneration (GTR) procedures in patients with periodontal osseous defects compared with surgical controls on clinical, radiographic, adverse, and patient-centered outcomes. It extends the scope of previous GTR systematic reviews, which were limited to randomized controlled studies, by the scope of outcome measures examined, and the duration of the study. FOCUSED QUESTION: In patients with periodontal osseous defects, what is the effect of physical barriers compared with surgical controls on clinical, radiographic, adverse, and patient-centered outcomes? SEARCH PROTOCOL: An electronic search of the Cochrane Oral Health Group Trials Register and MEDLINE databases was performed. Manual searching of journals included Journal of Clinical Periodontology, Journal of Periodontology, and Journal of Periodontal Research up to January 2002. This manual search also included review of relevant bibliographies. Two manufacturers of GTR devices were contacted regarding unpublished data. SELECTION CRITERIA INCLUSION CRITERIA: Studies were selected for review if the evidence level was 3B (cohort) or above, at least 6 months duration, and compared a test GTR intervention with a surgical control. EXCLUSION CRITERIA: Studies with experimental design problems; histologic or microbiological investigations; or those with outcome measurements, study populations, or study duration not consistent with the inclusion criteria were excluded. Primary outcome measures for intrabony defects were: clinical attachment level (CAL) gain, probing depth reduction (PD), gingival recession (REC) reduction; for furcation defects: vertical probing attachment level (VPAL) gain, vertical probing depth reduction (VPD), horizontal probing depth reduction (HPD), horizontal open probing attachment level gain (HOPA), and vertical open probing attachment level gain (VOPA). Meta-analysis was performed to compare GTR procedures to other surgical treatments and to examine the resulting clinical outcomes. MAIN RESULTS: 1. For the primary outcome variables, in both intrabony-defect and furcation-defect studies, GTR was favored over open flap debridement (OFD) therapies (P < 0.0001). 2. No differences were detected among barrier types, but barrier types could explain some heterogeneity in the results. 3. Augmentation of the GTR barrier with a particulate graft enhanced VPD (P < 0.05), VPAL, and HOPA, but none of the intrabony outcomes. REVIEWER'S CONCLUSIONS: Overall, GTR is consistently more effective than OFD in the gain of clinical attachment and probing depth reduction in the treatment of intrabony and furcation defects.

Absorbable Implants↗

PubMed2001

A primary care approach to treating women without homes.

Medical practitioners are encountering more women who are presently or formerly homeless. Homelessness negatively affects health and health outcomes. Women without homes experience repeated violence and trauma. In this review, the definition and scope of homelessness as it impacts women is discussed, from the etiology of women's homelessness to a description of their lifestyle. A paradigm of a primary care approach to understanding and treating women without homes is presented, including strategies for history taking, physical exams, and follow-up care that help build trust and improve compliance.

Continuity of Patient Care↗

PubMed2002

Towards patient-specific tumor antigen selection for vaccination.

In this review, we discuss the possibilities for combining the power of molecular analysis of the antigens expressed in a given individual tumor with the design of a tailored vaccine containing defined antigens. Step 1 is a differential gene expression analysis of tumor and corresponding normal tissue. Step 2 is the analysis of human leukocyte antigen (HLA) ligands on tumor cells. Step 3 is data mining with the aim to select those antigens that might be suitable for tumor attack by the adaptive immune system. Step 4 is the on-the-spot clinical grade production of the constituents of the patient tailored vaccine, e.g. peptides. Step 5 is then vaccination and monitoring. Although it will not be possible to cover all relevant antigens expressed in a tumor, the antigens that can be identified with our present technical possibilities might be enough for improved immunotherapy. The scope of the present review is to explore the possibilities and the formidable technical and logistical challenge for such individual patient-oriented antigen definition to be used for therapeutic immunization.

Algorithms↗

PubMed2006

Using protein homology models for structure-based studies: approaches to model refinement.

Homology modeling is a computational methodology to assign a 3-D structure to a target protein when experimental data are not available. The methodology uses another protein with a known structure that shares some sequence identity with the target as a template. The crudest approach is to thread the target protein backbone atoms over the backbone atoms of the template protein, but necessary refinement methods are needed to produce realistic models. In this mini-review anchored within the scope of drug design, we show the validity of using homology models of proteins in the discovery of binders for potential therapeutic targets. We also report several different approaches to homology model refinement, going from very simple to the most elaborate. Results show that refinement approaches are system dependent and that more elaborate methodologies do not always correlate with better performances from built homology models.

Computational Biology↗

PubMed2001

Surfing the insulin signaling web.

The diverse biological actions of insulin and insulin-like growth factor I (IGF-I) are initiated by binding of the polypeptides to their respective cell surface tyrosine kinase receptors. These activated receptors phosphorylate a series of endogenous substrates on tyrosine, amongst which the insulin receptor substrate (IRS) proteins are the best characterized. Their phosphotyrosine-containing motifs become binding sites for Src homology 2 (SH2) domains on proteins such as SH2 domain-containing protein-tyrosine-phosphatase (SHP)-2/Syp, growth factor receptor bound-2 protein, (Grb-2), and phosphatidyl inositol 3 kinase (PI3 kinase), which participate in activation of specific signaling cascades. However, the IRS molecules are not only platforms for signaling molecules, they also orchestrate the generation of signal specificity, integration of signals induced by several extracellular stimuli, and signal termination and modulation. An extensive review is beyond the scope of the present article, which will be centered on our own contribution and reflect our biases.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

[Neurological evaluation of behavior].

INTRODUCTION: The evaluation of behavior is becoming increasingly important in neurology, mainly because the behavior disorders are an important factor in overburdening carers and leading to institutionalization of patients with dementia. DEVELOPMENT: In this article we review the methodology and scope of the evaluation of conduct in cognitive deterioration and in dementia, with special attention to Alzheimer's disease. We also describe the instruments for evaluation which the author considers to be most relevant. From an initial broad concept, the scales of evaluation have been reduced to a limited concept of behavior disorder, which is an equivalent phenomenon to a 'psychiatric disorder'. The behavioral manifestations of the different dementias overlap completely, so that there is only limited usefulness in the evaluation of behavior for differential diagnosis. However, detailed evaluation of behavior contributes to a more rational approach to these patients, which would reduce the career's burden. CONCLUSION: Development of sensitive scales during all the phases of deterioration and of instruments which allow one to investigate the genesis of the different disorders are urgently needed, preferably with an intercultural approach.

Aged↗

PubMed2005

An integrative review of interventions for adolescent weight loss.

The number of overweight adolescents aged 12-19 has tripled during the past 2 decades. Although health risks associated with obesity in adolescence and adulthood are well documented in the literature, little is known about the efficacy of interventions to reduce health risks of this group. The purpose of this study was to conduct a systematic review to describe the scope, domain, and effectiveness of weight loss interventions with overweight adolescents. English-language journal articles published in nursing, psychology, nutrition, medicine, and exercise physiology literature between 1980 and 2003 were retrieved. Seventeen studies using comparison or control groups and interventions directed at reductions in adolescent body mass index or body weight were identified. Descriptive findings of those studies are reported here. Five specific limitations of these studies emerged from the analysis of the interventions: the study findings have not been validated by replication, the samples failed to include adequate representation of Latino and African American male participants, family participation in studies has been inconsistent and infrequent, there is a need for attention to study dropout rates (with attrition reported as high as 45%), and there is a need for conceptual frameworks to guide the studies.

Adolescent↗

PubMed2004

Review article: pathogenesis and pathophysiology of hepatorenal syndrome--is there scope for prevention?

The hepatorenal syndrome (HRS) is a functional impairment of the kidneys in chronic liver disease caused by a circulatory failure. The prognosis is poor, particularly with type 1 HRS, but also type 2, and only liver transplantation is of lasting benefit. However, recent research into the pathophysiology of ascites and HRS has stimulated new enthusiasm in their prevention and treatment. Patients with HRS have hyperdynamic circulatory dysfunction with reduced arterial blood pressure and reduced central blood volume, owing to preferential splanchnic arterial vasodilatation. Activation of potent vasoconstricting systems, including the sympathetic nervous and renin-angiotensin-aldosterone systems, counteracts the arterial vasodilatation and leads to a pronounced renal vasoconstriction with renal hypoperfusion, a reduced glomerular filtration rate, and intense sodium-water retention. Thus prevention of HRS should seek to improve liver function, limit arterial hypotension and central hypovolaemia, and reduce renal vasoconstriction and the renal and interstitial pressures. Portal pressure can be reduced with beta-adrenergic blockers and transjugular intrahepatic portosystemic shunt (TIPS). Precipitating events, like infections, bleeding, and postparacentesis circulatory syndrome, should be treated to avoid further circulatory failure. Improvement in arterial blood pressure and central hypovolaemia can be achieved with vasoconstrictors, such as terlipressin (Glypressin), and plasma expanders such as human albumin. In the future endothelins, adenosine antagonists, long-acting vasoconstrictors, and antileukotriene drugs may play a role in preventing and treating HRS.

Arginine Vasopressin↗

PubMed2003

The role of organic solvents in the separation of nonionic compounds by capillary electrophoresis.

Although nonionic compounds can be separated by micellar electrokinetic chromatography (MEKC), application of this technique is restricted by a somewhat limited elution range. Incorporation of organic solvents in the background electrolyte (BGE) greatly extends the scope of MEKC and provides a major variable in optimizing the separation of neutral analytes. This paper provides a systematic review of the principles and scope of the separation of neutral analytes by capillary electrophoresis (CE) in organic-aqueous solution. The methods surveyed include those that use tetraalkylammonium salts, dioctyl sulfosuccinate, lauryl poly(oxyethylene) sulfate. Polyaromatic hydrocarbon (PAH) compounds can be separated using sodium hexadecyl sulfate in 70% methanol (30% aqueous) to 100% methanol.

Chromatography, Micellar Electrokinetic Capillary↗

PubMedDate not supplied

The multilayered postconfluent cell culture as a model for drug screening.

New drug development requires simple in vitro models that resemble the in vivo situation more in order to select active drugs against solid tumours and to decrease the use of experimental animals. In this paper, we review the characteristics and scope of a relatively simple cell-culture system with a three-dimensional organisation pattern - the multilayered postconfluent cell culture model. Solid tumour cell lines from diverse origins when grown in V-bottomed microtiter plates reach confluence in 3-5 days and then start to form multilayers. The initial exponential growth of the culture is followed by a plateau phase when cells reach confluence. This produces changes in the morphology of the cells. For some cell lines, it is possible to observe cell differentiation. A substantial advantage of the system is the use of the sulforodamine B (SRB) assay to determine relative cell growth or viability, which allows semiautomation of the experiments. Several experiments were performed to assess the differences and similarities between cells cultured as monolayers and multilayers, and eventually, compared with the results for solid tumours and some other models such as spheroids. Cell-cycle analysis for multilayers showed a lower S-phase arrest, which is accompanied by a decrease in the expression of cell-cycle-related proteins and a decrease in cellular nucleotide pools. Gene and protein expression of topoisomerase I, topoisomerase II and thymidylate synthase expression were lower for multilayers, but no substantial changes were observed for the expression of DT-diaphorase. P53 expression increased. Multilayer cultures present distinctive properties for drug transport across the membrane, drug accumulation and retention. In fact, the transport of antifolates across the membrane, accumulation of topotecan and gemcitabine-triphosphate are reduced in multilayers when compared with monolayers, which may be related to a decrease in drug penetration to the inner regions of the multilayers. Alteration of these pharmacodynamic parameters is directly related to a decrease in drug activity. The most powerful application of multilayers is in the assessment of cytotoxicity. Solid tumour cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The data show that multilayers are more resistant to the drugs than the corresponding monolayers, but there are substantial differences between the drugs depending on culture conditions, e.g. the difference was rather small for a drug such as cisplatin, miltefosine and EO9, a drug, which is activated under hypoxic conditions. Gemcitabine was active against ovarian cancer but not against colon cancer, resembling the in vivo situation. This observation was not evident with monolayer experiments. Another interesting application is the possibility to perform drug combination studies. The combination of gemcitabine and cisplatin proved to produce selective cell kill in H322 cells (non-small cell lung cancer cell line). Neither of the drugs was independently able to produce similar effects. In summary, multilayer cultures are relatively simple three-dimensional systems to study the effect of microenvironmental conditions on anticancer drug activity. The model might serve as a base for a more rigorous secondary in vitro screening.

Animals↗

PubMed1998

Pathophysiology and treatment of diabetic neuropathy.

The scope of the present review is to describe epidemiology, classification, symptomatology and treatment of diabetic peripheral somatic neuropathy and autonomic neuropathy. Special attention is paid to the use of local anaesthetic agents in painful diabetic neuropathy. Denervation hypersensitivity is a characteristic of autonomic neuropathy in diabetic patients. The pathophysiology behind this phenomenon is elucidated in this review and most recent studies related to diabetic encephalopathy are reviewed. References for this review were acquired via a MedLine and MedLars literature search.

Autonomic Nervous System Diseases↗

PubMed1998

Promotion, prediction and prevention of progression of nephropathy in type 1 diabetes mellitus.

The scope of the present review is to discuss the prognosis of diabetic renal disease, putative progression promoters and the possibilities for treatment and prediction of treatment efficacy. The recent changes in the incidence of diabetic nephropathy in Type 1 diabetes mellitus are discussed. Promoters of progression in diabetic nephropathy are evaluated, in particular arterial blood pressure, glycaemic control, albuminuria and cholesterol levels. Potential treatment modalities are discussed, with special focus on antihypertensive therapy, including a discussion of a specific renoprotective action of certain antihypertensive agents. Furthermore putative predictors of treatment efficacy are evaluated, demonstrating that the ability to lower the urinary albumin excretion rate after onset of treatment heralds a slow progression of the renal disease. The prognosis in diabetic renal disease has improved with an increase in median survival after onset of nephropathy from 6 to 15 years. This has exposed the importance of cardiovascular morbidity and mortality. The identification and treatment of cardiovascular risk factors has become essential. Although the prognosis has improved remarkably, the primary goal should be prevention of diabetic nephropathy, as it is unlikely that the increased risks associated with this complication can be eliminated.

Animals↗

PubMed2006

Brief review: angiotensin converting enzyme inhibitors and angioedema: anesthetic implications.

PURPOSE: Angiotensin converting enzyme inhibitors (ACEIs) are a group of drugs used to treat hypertension and heart failure, with additional benefits, such as cardiovascular and renal protection, in patients with diabetes. However, angioedema as a complication of ACEI therapy is under-recognized. As there are important implications for anesthesiologists and emergency medicine physicians, a review was undertaken to document the scope of the problem of ACEI-induced angioedema.. METHODS: A review of the published literature (identified by searching Medline, EMBASE and CINAHL) was undertaken, addressing the clinical uses of ACEIs and the incidence, risk factors, pathophysiology, clinical presentation and management of angioedema associated with the use of these drugs. PRINCIPAL FINDINGS: The incidence of ACEI related angioedema has increased from 0.1-0.2% to 1% over the last decade. Patients who are receiving ACEIs are predisposed to developing angioedema which may be triggered by trauma, airway instrumentation, infection, and irritant fumes, particularly in those who are at increased risk. Cases of acute facial and airway oedema, due to ACEI drug administration, may be misdiagnosed as an anaphylactic reaction, and the association with ACEIs may be ignored. Some cases of intraoperative and postoperative airway edema may be precipitated by airway instrumentation in patients receiving ACEI drugs. The severity of airway compromise ranges from mild facial edema to severe laryngeal or subglottic edema which may prove life-threatening. CONCLUSION: In view of the widespread clinical indications and ever-increasing use of ACEI drugs, the potentially life-threatening adverse reaction of ACEI-associated angioedema, and its treatment, must be recognized by anesthesiologists and all clinicians involved in airway management.

Angioedema↗

PubMed1998

[Benign microglandular prostate lesions. Diagnostic criteria na differential diagnosis].

The scope of the present review is to define diagnostic criteria of benign prostatic lesions causing diagnostic difficulty in surgical pathology. The prostate harbors a variety of small acinar lesions that may mimic prostate cancer in biopsy specimens. Generally, the most important diagnostic clues are obtained on low-power magnification by assessing architectural features. Atypical adenomatous hyperplasia (AAH) is a small acinar proliferation closely related to hyperplastic glands. Diagnostic features of postatrophic hyperplasia include a lobular small acinar proliferation associated with atrophic and dilated acini. Basal cell hyperplasia and sclerosing adenosis show characteristic stromal changes that are uncommon in prostate cancer. Additional cytological features and intraluminal secretions are also important in the diagnostic evaluation of small acinar lesions in biopsy specimens. Negative immunohistochemical results obtained with basal-cell-specific cytokeratins should be evaluated in context with other diagnostic criteria. The unequivocal demonstration of basal cells in small acinar lesions excludes invasive cancer. Other rare small acinar lesions must be recognized when assessing biopsy specimens, including verumontanum-mucosa hyperplasia, Cowper's glands and mesonephroid hyperplasia. The various small acinar lesions discussed in the present review have no clinical significance, except atypical adenomatous hyperplasia (AAH), which may be a precursor of small acinar cancer of the transition zone. The biological and clinical significance of AAH, however, remains to be established.

Atrophy↗

PubMed2006

Delivery of viral vectors to tumor cells: extracellular transport, systemic distribution, and strategies for improvement.

It is a challenge to deliver therapeutic genes to tumor cells using viral vectors because (i) the size of these vectors are close to or larger than the space between fibers in extracellular matrix and (ii) viral proteins are potentially toxic in normal tissues. In general, gene delivery is hindered by various physiological barriers to virus transport from the site of injection to the nucleus of tumor cells and is limited by normal tissue tolerance of toxicity determined by local concentrations of transgene products and viral proteins. To illustrate the obstacles encountered in the delivery and yet limit the scope of discussion, this review focuses only on extracellular transport in solid tumors and distribution of viral vectors in normal organs after they are injected intravenously or intratumorally. This review also discusses current strategies for improving intratumoral transport and specificity of viral vectors.

Animals↗

PubMed2026

Advances in cereal protein applications for infant and Young child nutrition.

BACKGROUND: The increasing use of plant-derived proteins in infant and young child nutrition necessitates tailored amino acid profiles, high digestibility and strict safety controls. Cereal proteins, such as rice, oat, maize, millet, barley, and wheat, are widely used in complementary foods but face intrinsic limitations, notably lysine and tryptophan deficits, antinutritional factors that reduce bioavailability, gluten immunogenicity in wheat/barley, and inorganic arsenic risks in rice. SCOPE AND APPROACH: This review synthesizes recent advances in processing and formulation strategies, including enzymatic hydrolysis, fermentation, germination, extrusion, cereal-legume complementation, and micronutrient fortification. Their impacts on digestibility, techno-functionality, iron and zinc bioavailability, and protein quality, including Protein Digestibility-Corrected Amino Acid Score (PDCAAS) and Digestible Indispensable Amino Acid Score (DIAAS) are critically reviewed using data from in vitro assays, product development, and clinical trials. KEY FINDINGS AND CONCLUSIONS: Processing and blending approaches can substantially improve protein digestibility, amino acid balance and micronutrient availability, and hydrolyzed rice protein holds clinical promise for cow's milk protein allergy (CMPA). However, most evidence is preclinical, reporting of protein quality is inconsistent, and industrial translation is constrained by sensory, shelf-life, contaminant and cost issues. We recommend standardized DIAAS-based reporting, large-scale feeding trials, sensory /stability optimization, and targeted exploration of underutilized grains (e.g., oat, millet) with active allergen monitoring. Prioritizing amino acid-focused formulation coupled with strategies to enhance micronutrient bioavailability will accelerate safe adoption of cereal proteins in early-life nutrition.

Humans↗

PubMed2005

Prediction of endometrial carcinoma by subjective endometrial intraepithelial neoplasia diagnosis.

Endometrial intraepithelial neoplasia (also known as 'EIN') is a precursor to endometrioid endometrial adenocarcinoma characterized by monoclonal growth of mutated cells, a distinctive histopathologic appearance, and 45-fold elevated cancer risk. We have applied diagnostic criteria for EIN to 97 successive endometrial biopsies classified as hyperplastic according to World Health Organization criteria and correlated results with computer-assisted morphometry (D-score) and clinical cancer outcomes. Three pathologists separately reviewed all cases for presence or absence of EIN using published criteria (gland area>stromal area, cytologic change in focus of altered architecture, lesion size>1 mm, and exclusion of cancer and mimics). Discordant cases were resolved by a consensus review at a multiheaded scope. Clinical outcomes were obtained in 84 patients from patient visit and pathology records. Diagnoses of presence or absence of EIN were unanimous among all three pathologists in 75% of cases, and intraobserver-reproducibility was very good (kappa 0.73-0.90). Cases rediagnosed as EIN encompassed hyperplasias previously diagnosed as atypical (n=18) or nonatypical (eight complex, two simple). Eight follow-up cancers were scattered between hyperplasia types (5/21 atypical, 3/63 nonatypical), but all classified as EIN (8/25) and D-score <or=1 (8/38). Subjective application of criteria for diagnosis of EIN correlates well with objective morphometry and successfully segregates patients into high and low cancer risk subgroups with better reproducibility than atypical hyperplasia diagnosis.

Diagnosis, Computer-Assisted↗