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At least 667 records · Page 37Linked to original sources
PubMed2006

Double-J stent insertion across vesicoureteral junction--is it a valuable initial approach in neonates and infants with severe primary nonrefluxing megaureter?

OBJECTIVES: To evaluate the role of double-J stent insertion in perinatally detected primary nonrefluxing megaureters as a method to temporize treatment in patients with impaired renal function or to prevent function loss in patients treated expectantly, but deemed at high risk of deterioration. METHODS: Two neonates and 8 infants with a ureter greater than 10 mm and an obstructive excretion pattern, including 3 cases with renal function less than 40%, were selected to undergo double-J stent insertion for a 6-month period. Patients underwent surgery if the ureter redilated and the excretion pattern was obstructive at reassessment 3 months after stent removal. RESULTS: Stents were placed at a median age of 3 months (range 1 to 6). Open insertion was necessary in 5 cases (50%). Seven patients (70%) developed stent-related complications (five breakthrough urinary infections) requiring early stent removal in 2 (20%). Five patients (50%) underwent surgery at a median age of 14 months (range 13 to 27), including the 3 patients with decreased renal function at presentation. None required ureteral tapering. None experienced any renal function loss with respect to the initial evaluation. CONCLUSIONS: Double-J stent insertion across the vesicoureteral junction allows for effective internal drainage of primary nonrefluxing megaureters, but at the cost of a 70% morbidity rate and various technical drawbacks. Therefore, stenting should be considered on a case-by-case basis. The procedure seems valuable to temporize surgery in patients with decreased renal function. However, given the associated morbidity, it seems impractical for patients with preserved function selected in accordance with currently available prognostic indicators.

Female↗
PubMed2004

Mapping of sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function.

We have identified a lethal phenotype characterized by sudden infant death (from cardiac and respiratory arrest) with dysgenesis of the testes in males [Online Mendelian Inheritance in Man (OMIM) accession no. 608800]. Twenty-one affected individuals with this autosomal recessive syndrome were ascertained in nine separate sibships among the Old Order Amish. High-density single-nucleotide polymorphism (SNP) genotyping arrays containing 11,555 single-nucleotide polymorphisms evenly distributed across the human genome were used to map the disease locus. A genome-wide autozygosity scan localized the disease gene to a 3.6-Mb interval on chromosome 6q22.1-q22.31. This interval contained 27 genes, including two testis-specific Y-like genes (TSPYL and TSPYL4) of unknown function. Sequence analysis of the TSPYL gene in affected individuals identified a homozygous frameshift mutation (457_458insG) at codon 153, resulting in truncation of translation at codon 169. Truncation leads to loss of a peptide domain with strong homology to the nucleosome assembly protein family. GFP-fusion expression constructs were constructed and illustrated loss of nuclear localization of truncated TSPYL, suggesting loss of a nuclear localization patch in addition to loss of the nucleosome assembly domain. These results shed light on the pathogenesis of a disorder of sexual differentiation and brainstem-mediated sudden death, as well as give insight into a mechanism of transcriptional regulation.

Active Transport, Cell Nucleus↗
PubMed1995

[Effect of variations in middle ear pressure on ruptures of the round window membrane of the inner ear of the guinea pig (Cavia porcellus)].

The electrical activity of the inner ear before and after rupture of the round window membrane was monitored in guinea pigs under different pressure conditions with the aid of electrocochleography. Following studies were conducted weekly over a period of 4 weeks. Findings showed that overpressure below the pressure needed to open the Eustachian tube caused strong temporary functional disturbance of the cochlea, especially at high frequencies. Irreversible changes that were pressure-dependent were observed and occurred mainly at high frequencies. Application of low pressure to the round window membrane caused a functional loss comparable to changes after overpressure. Animals with a predamaged cochlea reacted to overpressure that was below opening pressure of the tube and to corresponding low pressure with a longer lasting functional loss than did animals with an undamaged cochlea.

Acoustic Impedance Tests↗
PubMed1998

Bayesian variable selection method for censored survival data.

A Bayesian variable selection method for censored data is proposed in this paper. Based on the sufficiency and asymptotic normality of the maximum partial likelihood estimator, we approximate the posterior distribution of the parameters in a proportional hazards model. We consider a parsimonious model as the full model with some covariates unobserved and replaced by their conditional expected values. A loss function based on the posterior expected estimation error of the log-risk for the proportional hazards model is used to select a parsimonious model. We derive computational expressions for this loss function for both continuous and binary covariates. This approach provides an extension of Lindley's (1968, Journal of the Royal Statistical Society, Series B 30, 31-66) variable selection criterion for the linear case. Data from a randomized clinical trial of patients with primary biliary cirrhosis of the liver (PBC) (Fleming and Harrington, 1991, Counting Processes and Survival Analysis) is used to illustrate the proposed method and a simulation study compares it with the backward elimination procedure.

Bayes Theorem↗
PubMed2005

The Glenn A. Fry Award Lecture 2003: Vision in elders--summary of findings of the SKI study.

PURPOSE: To assess a broad range of vision functions in a large older population, to investigate the impact of vision function loss on visual performance measures, and to determine whether low contrast vision measures can predict future loss of visual acuity. METHODS: A large battery of vision functions, including spatial vision measures, glare tests, visual fields, stereopsis, color vision, temporal sensitivity, reading performance, and face recognition, was administered to a population of 900 community-living older observers (mean age, 75.5 years; SD, 9.3 years; range, 58 to 102 years). A subsample (N = 596) was retested on average 4.4 years later (SD, 1.0 years). RESULTS: Each vision function is affected differentially by aging. Some functions show little change with age (e.g., standard clinically measured high contrast visual acuity), whereas others demonstrate drastic losses with increasing age. For the oldest age group (>90 years), vision function losses ranged from 1.2 times worse than young observers (critical flicker/fusion frequency) to 18 times worse than young observers (low contrast acuity in glare). Visual performance measures, such as reading or face recognition, are also significantly affected by aging even in those with intact visual acuity. The results demonstrate that low contrast vision functions can successfully predict subsequent loss of high contrast visual acuity. CONCLUSION: Nonstandard vision function measures show significant losses with age that cannot be predicted by standard clinical measures. Measures of low contrast vision function allow clinicians to identify and monitor those patients at high risk for future vision loss.

Aged↗
PubMed1999

Neutrophil-specific granule deficiency results from a novel mutation with loss of function of the transcription factor CCAAT/enhancer binding protein epsilon.

Neutrophil-specific granule deficiency (SGD) is a rare disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. CCAAT/enhancer binding protein (C/EBP)epsilon, a member of the leucine zipper family of transcription factors, is expressed primarily in myeloid cells, and its knockout mouse model possesses distinctive defects, including a lack of neutrophil secondary granule proteins. Sequence analysis of the genomic DNA of a patient with SGD revealed a five-basepair deletion in the second exon of the C/EBPepsilon locus. The predicted frame shift results in a truncation of the 32-kD major C/EBPepsilon isoform, with loss of the dimerization domain, DNA binding region, and transcriptional activity. The multiple functional defects observed in these early neutrophil progenitor cells, a consequence of C/EBPepsilon deficiency, define SGD as a defect in myelopoiesis and establish the requirement for C/EBPepsilon for the promyelocyte-myelocyte transition in myeloid differentiation.

Animals↗
PubMed2007

Loss of functional ELOVL4 depletes very long-chain fatty acids (> or =C28) and the unique omega-O-acylceramides in skin leading to neonatal death.

Mutations in elongation of very long-chain fatty acid-4 (ELOVL4) are associated with autosomal dominant Stargardt-like macular degeneration (STGD3), with a five base-pair (5 bp) deletion mutation resulting in the loss of 51 carboxy-terminal amino acids and truncation of the protein. In addition to the retina, Elovl4 is expressed in a limited number of mammalian tissues, including skin, with unknown function(s). We generated a knock-in mouse model with the 5-bp deletion in the Elovl4 gene. As anticipated, mice carrying this mutation in the heterozygous state (Elovl4(+/del)) exhibit progressive photoreceptor degeneration. Unexpectedly, homozygous mice (Elovl4(del/del)) display scaly, wrinkled skin, have severely compromised epidermal permeability barrier function, and die within a few hours after birth. Histopathological evaluation of the Elovl4(del/del) pups revealed no apparent abnormality(ies) in vital internal organs. However, skin histology showed an abnormally-compacted outer epidermis [stratum corneum (SC)], while electron microscopy revealed deficient epidermal lamellar body contents, and lack of normal SC lamellar membranes that are essential for permeability barrier function. Lipid analyses of epidermis from Elovl4(del/del) mice revealed a global decrease in very long-chain fatty acids (VLFAs) (i.e., carbon chain > or =C28) in both the ceramide/glucosylceramide and the free fatty-acid fractions. Strikingly, Elovl4(del/del) skin was devoid of the epidermal-unique omega-O-acylceramides, that are key hydrophobic components of the extracellular lamellar membranes in mammalian SC. These findings demonstrate that ELOVL4 is required for generating VLFA critical for epidermal barrier function, and that the lack of epidermal omega-O-acylceramides is incompatible with survival in a desiccating environment.

Animals↗
PubMedDate not supplied

French survey of postpolio sequelae. Risk factors study and medical social outcome.

For 10 yr, numerous studies have been conducted to try to explain the further deterioration of the sequelae from a previous, acute poliomyelitis. The different etiologic hypotheses, which have been put forward, have not been confirmed yet. A retrospective study has been completed by mailed questionnaires sent to 360 patients previously affected by acute polio; 248 polio survivors replied. Deterioration, as functional loss especially during walking and exertion, was reported by 77% of our respondents. Among the newly affected cases, 60% have given up or slowed down their socio-professional activities because of these new problems with their health. These functional losses, reported by patients, have been statistically related to several factors: the aging process, weight gain, female predominance and the involvement of abdominal muscles at a previously acute polio stage. The recently affected population has the same degree of disability (measured through the "Functional Independence Measure" (translated in French and self-administered)) as the nonaffected one. This fact suggests that the problems that are being experienced may be partly subjective.

Abdominal Muscles↗
PubMed1999

The role of possible risk factors for acute and late renal dysfunction after high-dose interleukin-2, interferon alpha and lymphokine-activated killer cells.

Renal dysfunction is a frequently encountered adverse event following treatment with high-dose interleukin-2 (IL-2). Information about parameters predicting the severity of IL-2-associated renal function abnormalities is limited. In this study the role of possible risk factors in the development of high-dose IL-2-associated acute and long-term renal dysfunction was investigated. A total of 72 patients, who were treated with a regimen consisting of IL-2 (18 MIU m(-2) day(-1) by continuous infusion), interferon alpha (IFNalpha; 5 MIU m(-2) day(-1), intramuscularly) and lymphokine-activated killer (LAK) lymphocytes, were analysed. Serum creatinine measurements were performed daily during treatment, weekly between courses and monthly during follow-up. Pre-and posttreatment 24-h urine samples were collected for calculation of creatinine clearances. Renal dysfunction was observed in 97% of patients. Grade 1 dysfunction (according to WHO criteria) was observed in 20 patients (28%), grade 2 in 37 (51%), grade 3 in 13 (14%) and grade 4 in 0 (0%). Renal dysfunction was reversible in more than 90% of patients. Only 6 patients (8%) suffered a certain amount of permanent function loss. More severe acute renal dysfunction occurred in patients who were experiencing hypertension prior to treatment, those who suffered sepsis during treatment and in men than in women. Sepsis was also associated with irreversible function loss. Other variables such as age, performance status, diabetes mellitus, interval between nephrectomy and start of IL-2 therapy and hypotension during treatment were not important. In conclusion, with high-dose IL-2, renal dysfunction develops in almost every patient and such abnormalities are mostly reversible. Predictors for severe acute renal dysfunction are pre-existing hypertension, sepsis and sex. A septic episode also carries a risk of permanent damage.

Adult↗
PubMed2003

A novel loss-of-function mutation (N48K) in the PTEN gene in a Spanish patient with Cowden disease.

Cowden disease, also known as multiple hamartoma syndrome, is a rare disease inherited in an autosomal dominant pattern, which confers a high risk of developing breast and thyroid carcinomas. Mutations in PTEN, a tumor suppressor gene located on chromosome 10q23, have been identified in patients with Cowden disease. In this work, the direct sequencing of all coding regions of the PTEN gene led us to the identification of N48K, a new germline PTEN missense mutation, in a patient suffering from Cowden disease. The genetic analysis of 200 chromosomes from healthy individuals revealed that the variant was not common in our population. Moreover, by functional analysis we found that the ability of PTEN N48K mutant protein to inhibit the activation of the proto-oncogene PKB/Akt was impaired, supporting the involvement of N48K mutation in Cowden disease. Loss of heterozygosity using three microsatellites (D10S215, D10S541, and D10S564) and the complete sequence analysis of PTEN exons in breast and endometrial tumor samples from the same patient were also carried out in an attempt to identify additional PTEN somatic mutations. The lack of loss of heterozygosity or additional mutations in tumor samples suggests that abnormalities of the regulatory regions of the PTEN gene or haplo-insufficiency might occur in tumors from Cowden disease patients.

Adult↗
PubMed1988

Evaluation of functional capacity after stroke with special emphasis on motor function and activities of daily living.

In a multidisciplinary study comprising 280 patients with acute cerebrovascular disease (median age 76, range 30-96 years), instruments for functional assessment in stroke care were developed. The improvements of motor function and activities of daily living were investigated during a period of up to one year after a stroke. A new chart for motor capacity assessment, which includes both the paretic and the non-paretic side, modified after that of Fugl-Meyer et al, was tested for its reliability and validity. At the same time the Activity Index of Hamrin & Wohlin was further tested. The internal consistency reliability measured with the standardized item alpha method confirmed that the two instruments have high homogeneity. Construct validity was investigated by factor analysis and showed a logical structure. The predictive validity of the scores on admission was significant and the two tools had a satisfactory predictive capacity for survival and later functional outcome. The improvements in different motor functions were followed up for up to one year after the stroke among the 183 one-year survivors. In patients with minor impairment, the improvement occurred mostly during the first week. Patients with moderate or moderately severe impairment improved more continuously for up to three months, while the few surviving patients with very severe impairment continued to recover to some extent even after three months. Older patients with severe functional loss seemed to improve more slowly and not as well as younger patients with equivalent impairment. The patterns of instrumental activities of daily living (I-ADL), such as household work, locomotion, psychosocial functions and intellectual activities, were investigated in the 207 three-month survivors and the 183 one-year survivors. At both the three-month and the one-year follow-ups the scores had decreased considerably, compared with before the stroke, for all activities except locomotion, and many patients were dependent on somebody else for help. The same group of patients was also examined by a Standardized Practical Equipment (SPE) test constructed by Tömquist three months and one year after the stroke. The construct validity of the SPE test was estimated through factor analysis. Three factors emerged, one concerning mainly cognitive factors and co-ordination, one concerning hand function and one concerning mainly mobility and balance. The instruments developed in the course of this study have proved to be reliable and valid, and useful in assessing functional losses and following progress. The tools are well suited for any clinical settings and for home care examinations as well as research.

Activities of Daily Living↗
PubMed1993

Musculo-tendinous transfers of the hand and forearm.

The concept of providing a more equitable distribution of forces acting upon a disabled limb is the basis of tendon transfers. The musculo-tendinous transfer is usually performed by moving the insertion, thereby altering the direction of the unit in an attempt to replace a lost function. In order to obtain a successful result basic principles have to be followed. The transferred muscle must have enough strength, should have approximately the same amplitude as the muscle whose function it is replacing and should have a straight line of pull from the origin to the new insertion or distally from the newly created pulley. Furthermore, the nerve and blood supply should remain intact during the actual transfer. In the event of scarred tissue or poorly mobilized joints treatment should first deal with these problems before tendon transfer is carried out. After careful assessment of the patient's disability a plan of operation can be conceived on the basis of the extent of functional loss balanced against the muscle force available for transfer. Essential for forearm and hand function are wrist extension and finger flexion as well as thumb and intrinsic function. The loss of these functions may be compensated for by a variety of motors. The choice is made on the basis of the available possibilities and the demands of the patient. To obtain optimal postoperative results physiotherapy of the hand and a well motivated patient are necessary.

Combined Modality Therapy↗
PubMed1981

Interrelationships between regional left ventricular function, coronary blood flow, and myocellular necrosis during the initial 24 hours and 1 week after experimental coronary occlusion in awake, unsedated dogs.

This study examined the relationships between the left ventricular (LV) regional function, regional myocardial blood flow (RMBF), and myocellular necrosis after sudden proximal occlusion of the left anterior descending coronary artery (LAD) in 36 awake, unsedated dogs. Net wall thickening during systole (NET) was used to assess regional LV function, was expressed as percent control, and was measured with chronically implanted ultrasonic crystals. RMBF was measured with 8- to 10-micrometer radioactive microspheres. In regions with a moderate degree of functional loss, NET fell to 35.3 +/- 2.2% of control at 5 minutes when RMBF fell from 1.9 +/- 0.08 to .086 +/- 0.09 ml/g per min (P less than 0.05). No significant change occurred in midwall or epicardial RMBF. The relationship between endocardial flow and NET was non-linear (r = 0.69, P less than 0.0001). In these segments, subsequent changes in RMBF were unrelated to corresponding functional alterations through 24 hours. In segments with paradoxic systolic wall thinning RMBF fell in endocardial, midwall, and epicardial layers; endocardial ischemia was most severe (0.30 +/- 0.05 ml/g per min). Segmental myocellular necrosis was most severe in the endocardial layer and correlated significantly with both RMBF and segmental function. Myocellular necrosis increased in severity as flow was reduced below 70-75% of normal. Thus, in this model of LV ischemia, (1) regional LV functional loss is most sensitive to reductions in endocardial RMBF; (2) subsequent increases in RMBF are largely unassociated with functional recovery; (3) transmural ischemia results in paradoxical systolic wall thinning.

Animals↗
PubMed1980

Preliminary studies on the validity of in vitro measurement of drug toxicity using HeLa cells. III. Lethal action to man of 43 drugs related to the HeLa cell toxicity of the lethal drug concentrations.

The human lethal plasma concentrations of 46 drugs were divided by their IC50 for HeLa cells in vitro to make up a series of cytotoxic quotients (CQLv). CQLv was then compared with the recorded lethal action to man of 43 of the drugs. While the 7 drugs with the lowest CQLv values produce a non-cytotoxic interference with neuro-transmission, most of the remaining 36 drugs have a known local or systemic cytotoxicity to man. A majority of the 36 drugs induces a non-specific central nervous system (CNS)-depression at lethal dosage, intermingled with function loss from organs outside CNS in proportion to decreasing drug accumulation in CNS cells and increasing CQLv. The remaining drugs which do not penetrate CNS cells and at lethal dosage induce a widespread injury and function loss of tissues outside the CNS, have a CQLv near unity. Non-specific CNS-depression may thus be the primary human reaction to lethal systemic drug cytotoxicity, while widespread drug injury to various tissues outside CNS--conventionally considered to be cytotoxic in origin--may be the obligatory human reaction to drugs that do not penetrate cells well. The present findings indicate a relevance to human toxicity of the HeLa toxicity for most drugs.

Cell Survival↗
PubMed2003

Preservation of base-line hemodynamic function and loss of inducible cardioprotection in adult mice lacking protein kinase C epsilon.

Signaling pathways involving protein kinase C isozymes are modulators of cardiovascular development and response to injury. Protein kinase C epsilon activation in cardiac myocytes reduces necrosis caused by coronary artery disease. However, it is unclear whether protein kinase C epsilon function is required for normal cardiac development or inducible protection against oxidative stress. Protein kinase C delta activation is also observed during cardiac preconditioning. However, its role as a promoter or inhibitor of injury is controversial. We examined hearts from protein kinase C epsilon knock-out mice under physiological conditions and during acute ischemia reperfusion. Null-mutant and wild-type mice displayed equivalent base-line morphology and hemodynamic function. Targeted disruption of the protein kinase C epsilon gene blocked cardioprotection caused by ischemic preconditioning and alpha(1)-adrenergic receptor stimulation. Protein kinase C delta activation increased in protein kinase C epsilon knock-out myocytes without altering resistance to injury. These observations support protein kinase C epsilon activation as an essential component of cardioprotective signaling. Our results favor protein kinase C delta activation as a mediator of normal growth. This study advances the understanding of cellular mechanisms responsible for preservation of myocardial integrity as potential targets for prevention and treatment of ischemic heart disease.

Animals↗
PubMed2005

Aging effects on vestibulo-ocular responses in C57BL/6 mice: comparison with alteration in auditory function.

Age-related changes in auditory function are well documented in animal models; however, this is not the case as regards vestibular function. In this study, we evaluated age-related changes in vestibulo-ocular responses in C57BL/6 mice that are considered as a model of presbycusis. The functional data were substantiated by the findings of histological analysis of vestibular and auditory peripherals. The gain in vestibulo-ocular reflex, which reflects functionality of the vestibular system, increased in an age-dependent manner until 12 weeks and exhibited limited functional loss due to aging after 24 weeks. By contrast, no alteration in the thresholds of the auditory brainstem response (ABR) was observed from 3 to 12 weeks of age; however, ABR thresholds were significantly elevated from age 24 weeks and onwards. Histological analysis demonstrated that the degeneration of auditory peripherals was closely related with functional loss due to aging. Vestibular peripherals also exhibited age-related degeneration morphologically, although age-related dysfunction was not apparent. Age-related changes in the vestibular function of C57BL/6 mice followed a different time course when compared to changes in auditory function. These findings indicate that mechanisms for age-related changes in vestibular function differ from those of auditory function.

Age Factors↗