Re: The graf ligamentoplasty procedure. Comparison with posterolateral fusion in the management of low-back pain.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
A Gardner
Publications and source records attributed to A Gardner.
Polymorphism of the ACE gene in Henoch-Schönlein purpura nephritis.
Individuals with IgA nephropathy (IgAN) who are homozygous for the deletion (D) polymorphism of the gene for angiotensin converting enzyme (ACE) are reported to be at increased risk of progressive renal damage. Since IgAN and Henoch-Schönlein purpura with associated nephritis (HSPN) share a common aetiology, we have investigated this influence in 31 children with HSPN. The distribution of genotypes was as follows: II: 4, ID: 17 and DD: 10 patients. Median length of follow-up was 4.5 years (range 0.5-15.75 years). Severe onset with nephrotic oedema and crescent formation on renal biopsy was seen in 10 of 17 patients with ID genotype and 5 of 10 patients with DD genotype. In the ID group, 2 patients have undergone renal transplantation and 4 have persistent proteinuria 4, 7, 9 and 10 years after presentation. One patient in the DD group has been transplanted and 1 patient has proteinuria and a reduced glomerular filtration rate 5 years after initial presentation. All other patients have either made a complete recovery or have microscopic haematuria alone. These results do not support an association between disease severity and DD genotype in children with HSPN; however larger studies are required to confirm this.
Child↗
Quality improvement of GI endoscopy--the "Endocard".
Explore the source record for details and available documents.
Endoscopy, Gastrointestinal↗
A national survey: transporting patients within Australian hospitals.
A telephone survey was conducted to describe current practices and policies of patient transport in Australian hospitals. The survey had a 94% response rate. Results showed considerable variability and ambiguity throughout the sample in both practice and policy. Findings also indicated that criteria used for transport practices were predominantly shaped by physiological and technological considerations. Factors related to human and financial resources, as well as psychological and emotional aspects of the patient's condition, received little attention.
Australia↗
Innovative thinking for the improvement of medical systems--"ENDOVIEW for the patients".
Explore the source record for details and available documents.
Computers↗
Relative cost of autologous red cell salvage versus allogeneic red cell transfusion during abdominal aortic aneurysm repair.
The costs of washed autologous red cell concentrate obtained by intraoperative red cell salvage were compared to the costs of allogeneic packed red cell transfusion during 110 consecutive abdominal aortic aneurysm repairs. The mean volume of scavenged blood during elective procedures was 1350 ml (range 350 to 6675 ml, n = 90) and emergency procedures 2750 ml (range 750 to 9400 ml, n = 20). The mean volume of processed (washed) blood returned during elective repairs was 759 ml (range 150 to 2900 ml, n = 51) and emergency repairs 1117 ml (range 0 to 4100 ml, n = 20). During elective repairs, the cost of routine autologous red cell salvage ($151 per 285 ml unit) was only slightly greater than the estimated cost of cross-matched, leucocyte-reduced, allogeneic blood ($143 per 285 ml unit). During emergency repairs, washed autologous red cells ($83 per 285 ml unit) were less expensive than allogeneic packed red cells. These findings indicate that, compared with the use of allogeneic packed red cells, red cell salvage during emergency abdominal aortic aneurysm repair can be justified on an economic basis alone, and that routine red cell salvage during elective repair can achieve the benefits of autologous blood at little extra cost to the community.
Aged↗
Literacy promotion in primary care pediatrics: can we make a difference?
BACKGROUND: Reading skills are critical to children's success in school and the increasingly technologic workforce. Children from low-income families are at risk for home environments that fail to promote emergent literacy and for reading failure. A home environment that encourages learning and parents who are involved in their children's education are important factors in school achievement. OBJECTIVE: To evaluate the effects of a literacy promoting intervention delivered by pediatric providers as part of well-child care on parent attitudes and behaviors and on child language. DESIGN/METHODS: A multicultural group of 205 low-income families with 5- to 11-month-olds were prospectively enrolled, interviewed, and randomized to intervention (n = 106) or control (n = 99) groups. Families in the intervention group received developmentally appropriate children's books and educational materials and advice about sharing books with children, while those in the control group received no books or materials relevant to literacy. After an average of 3.4 well-child visits in both groups, 153 (75%) were reinterviewed and the children's receptive and expressive vocabulary was tested using a modified version of the MacArthur Communication and Development Inventory (Short Form). Parents were asked if their child understood (receptive vocabulary) or said (expressive vocabulary) each of 100 words, half of which were in the books given. Families were found to have a Child-Centered Literacy Orientation if they mentioned reading aloud as one of their child's favorite activities or as one of their own favorite joint activities or if they usually read together at bedtime. At follow-up toddlers were 18.4 months old on average. RESULTS: Intervention and control groups had similar literacy related characteristics at baseline. There was a 40% increase in Child-Centered Literacy Orientation among intervention families compared with 16% among controls. Intervention families read more with their toddlers (4.3 vs 3.8 days/week). Both receptive and expressive vocabulary scores were higher in older intervention toddlers (18-25 months old; n = 88), but not in younger intervention toddlers (13-17 months old; n = 62). This significant effect of the intervention on vocabulary scores in older toddlers was found for both the 50 words in the books and those not in the books. After parent education, foreign birth and language proficiency, and child age were statistically controlled, the intervention remained significantly associated with higher language outcomes in older toddlers. However, when reading aloud was added to the multivariate analysis, the influence of the intervention was no longer evident, suggesting the intervention's effect on child language was mediated through increased shared reading with these toddlers. CONCLUSION: This simple and inexpensive intervention, delivered as part of well-child care, changed parent attitudes toward the importance of reading with their infants and toddlers. These intervention parents and their children read more together and this was associated with enhanced language development in older toddlers in this diverse group of low-income families.
Books↗
Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.
We report on a male newborn infant, a compound carrier of heterozygous mutations in the FGFR3 gene causing achondroplasia and hypochondroplasia. The mother has achondroplasia and carries the common G1138 (G380R) mutation in the FGFR3 gene; the father has hypochondroplasia due to the C1620A (N540K) mutation in the same gene. The fetus was found to carry both mutations diagnosed prenatally by amniocentesis at 17.6 weeks of gestation, following maternal serum screening which showed an increased risk for Down syndrome (1:337). Detailed fetal ultrasound studies showed a large head, short limbs, and a small chest at 22 weeks of gestation. The changes were more severe than those of either achondroplasia or hypochondroplasia. The patient was born by cesarean section at 38 weeks of gestation and had rhizomelic shortness of the upper and lower limbs with excess skin folds, large head, enlarged fontanelles, frontal bossing, lumbar gibbus, trident position of the fingers, and a narrow chest with a horizontal line of demarcation at the narrowest area of the chest. Skeletal radiographs showed shortness of the long bones and flare of metaphyses. He had respiratory difficulties and was treated with nasal prongs. Seizures developed on day 2 of life and recurred on day 9 and responded to treatment with phenobarbital. Brain computed tomographic scan showed possible grey matter heterotopia, partial agenesis of the corpus callosum, and cortical dysplasia. To our knowledge, there are only two previously published cases of compound heterozygous achondroplasia-hypochondroplasia patients. The diagnosis was confirmed by DNA mutation analysis of the FGFR3 gene in both cases.
Abnormalities, Multiple↗
Elevated TCDD in chicken eggs and farm-raised catfish fed a diet with ball clay from a Southern United States mine.
The U.S. Food and Drug Administration (FDA) terminated the use of ball clay from a mine in Mississippi as an additive in animal feed after discovering nanogram per gram concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The FDA collected chicken eggs and farm-raised catfish in affected areas and throughout the remaining continental United States to assess levels of 2,3,7,8-TCDD. A new method using quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) measured the 2,3,7,8-TCDD levels in 42 catfish fillet composites, 3 Tilapia fillet composites, 46 chicken egg samples, and 6 chicken feeds. Six catfish composites and 20 egg samples had 2,3,7,8-TCDD concentrations significantly above 1.0 pg/g wet weight of fillet or whole egg. Farm-raised catfish not exposed to feed containing ball clay had a mean 2,3,7,8-TCDD concentration of 0.12 pg/g. The TCDD isomer pattern in ball clay differed from the TCDD isomer pattern in a fly ash sample and from the "chick edema factor" TCDD pattern in a sample of reference toxic fat used as a feed ingredient in the 1950s.
Aluminum Silicates↗
The effect of cigarette smoking status on six-minute walk distance in patients with intermittent claudication.
The purposes of the study were threefold: (1) to compare 6-minute walk performance as a measure of exercise tolerance among three different groups of peripheral arterial occlusive disease (PAOD) patients with intermittent claudication-current smokers, former smokers, and patients who have never smoked; (2) to identify important covariates that might affect the relationship between smoking and exercise in the PAOD population; (3) to determine whether differences among the three groups in 6-minute walk performance persist after statistically controlling for the significant covariates. Recruited into the study were 415 PAOD patients with intermittent claudication between the ages of 42 and 88 years. The self-reported smoking status consisted of 182 current smokers, 196 former smokers, and 37 patients who had never smoked. The authors recorded 6-minute walk distance, a reliable measurement of exercise tolerance in PAOD patients, as well as age, body composition, self-reported ambulatory function, self-reported physical activity, and standard peripheral hemodynamics. Nonsmokers walked significantly farther (413 +/- 14 m; mean +/- standard error) and took more steps (665 +/- 14 steps) than either current (352 +/- 7 m; 563 +/- 9 steps) or former smokers 370 +/- 7 m; 600 +/- 8 steps) (p<0.05). The nonsmokers had a higher ankle-brachial index (ABI) value (0.70 +/- 0.03) than patients who actively smoked 0.62 +/- 0.01 (p<0.03); the authors observed an inverse relationship between smoking history and self-reported physical activity (WIQ Distance Score: nonsmokers 51 +/- 6%, former smokers 38 +/- 3%, and smokers 32 +/- 2%) (p<0.01). From a multivariate perspective, ABI, physical activity, and perceived walking ability were the only independent predictors of 6-minute walk distance. Differences in the adjusted 6-minute walk distance among the nonsmokers (388 +/- 13 m), current smokers (359 +/- 6 m), and former smokers (368 +/-6 m) no longer remained after controlling statistically for these covariates. The findings suggest that 6-minute walk distance is a sensitive measure to detect differences in submaximal exercise performance between smoking and nonsmoking PAOD patients with intermittent claudication. Moreover, the group difference in the 6-minute walk distance is explained by group differences in walking perception, PAOD severity, and physical activity level.
Adult↗
Simple method for improving the precision of electrolyte measurements in vitreous humor.
Explore the source record for details and available documents.
Autopsy↗
Interleukin-6-induced inhibition of multiple myeloma cell apoptosis: support for the hypothesis that protection is mediated via inhibition of the JNK/SAPK pathway.
The mechanism by which interleukin-6 (IL-6) protects multiple myeloma (MM) plasma cells from apoptosis induced by anti-fas antibodies and dexamethasone was studied. Anti-apoptotic concentrations of IL-6 had no effect on cell-cycle distribution or activation of RAF-1 or ERK in dexamethasone- or anti-fas-treated 8226 and UCLA #1 MM cell lines. However, IL-6-dependent protection of viability correlated with an inhibition of dexamethasone- and anti-fas-induced activation of jun kinase (JNK) and AP-1 transactivation. To test the hypothesis that cytokine-induced protection was mediated through inhibition of JNK/c-jun, we also inhibited c-jun function in 8226 cells via introduction of a mutant dominant negative c-jun construct. Mutant c-jun-containing MM cells were also resistant to anti-fas-induced apoptosis but were significantly more sensitive to dexamethasone-induced apoptosis. These results support the notion that IL-6 protects MM cells against anti-fas through its inhibitory effects on JNK/c-jun but indicate protection against dexamethasone occurs through separate, yet unknown pathways.
Apoptosis↗
Inversin, a novel gene in the vertebrate left-right axis pathway, is partially deleted in the inv mouse.
Visceral left-right asymmetry occurs in all vertebrates, but the inversion of embryo turning (inv) mouse, which resulted following a random transgene insertion, is the only model in which these asymmetries are consistently reversed. We report positional cloning of the gene underlying this recessive phenotype. Although transgene insertion was accompanied by neighbouring deletion and duplication events, our YAC phenotype rescue studies indicate that the mutant phenotype results from the deletion. After extensively characterizing the 47-kb deleted region and flanking sequences from the wild-type mouse genome, we found evidence for only one gene sequence in the deleted region. We determined the full-length 5.5-kb cDNA sequence and identified 16 exons, of which exons 3-11 were eliminated by the deletion, causing a frameshift. The novel gene specifies a 1062-aa product with tandem ankyrin-like repeat sequences. Characterization of complementing and non-complementing YAC transgenic families revealed that correction of the inv mutant phenotype was concordant with integration and intact expression of this novel gene, which we have named inversin (Invs).
Amino Acid Sequence↗
In vitro cytoreductive effects on multiple myeloma cells induced by bisphosphonates.
In a double blind randomized study, the bisphosphonate drug Pamidronate (Aredia) significantly protected Durie-Salmon stage III multiple myeloma patients from osteolytic bone disease. In the patient sub-group on salvage chemotherapy. Pamidronate treatment was also significantly associated with prolonged survival. To test if this drug could induce direct antitumor effects, we exposed myeloma cells to increasing concentrations of Pamidronate or a more potent bisphosphonate, Zoledronate. A concentration- and time-dependent cytotoxic effect was detected on four of five myeloma cell lines as well as three specimens obtained directly from myeloma patients. Zoledronate-induced cytotoxicity was significantly greater than that of Pamidronate. Cytotoxicity could not be explained by bisphosphonate-induced chelation of extracellular calcium or secondary decrease in production of the myeloma growth factor interleukin-6. Morphological examination, DNA electrophoresis and cell cycle analysis indicated that the bisphosphonate-induced cytotoxic effect consisted of a combination of cytostasis and apoptotic myeloma cell death. Enforced expression of BCL-2 protected against the apoptotic death but not against cytostasis. Most cytotoxic effects were seen between 10 and 100 microM of drug. The results suggest a possible direct anti-tumor effect in myeloma patients treated with bisphosphonates which may participate in their significantly increased survival. This hypothesis should now be further tested in clinical trials.
Antineoplastic Agents↗
Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counseling, and prenatal diagnosis.
The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are caused by the loss of function of imprinted genes in proximal 15q. In approximately 2%-4% of patients, this loss of function is due to an imprinting defect. In some cases, the imprinting defect is the result of a parental imprint-switch failure caused by a microdeletion of the imprinting center (IC). Here we describe the molecular analysis of 13 PWS patients and 17 AS patients who have an imprinting defect but no IC deletion. Heteroduplex and partial sequence analysis did not reveal any point mutations of the known IC elements, either. Interestingly, all of these patients represent sporadic cases, and some share the paternal (PWS) or the maternal (AS) 15q11-q13 haplotype with an unaffected sib. In each of five PWS patients informative for the grandparental origin of the incorrectly imprinted chromosome region and four cases described elsewhere, the maternally imprinted paternal chromosome region was inherited from the paternal grandmother. This suggests that the grandmaternal imprint was not erased in the father's germ line. In seven informative AS patients reported here and in three previously reported patients, the paternally imprinted maternal chromosome region was inherited from either the maternal grandfather or the maternal grandmother. The latter finding is not compatible with an imprint-switch failure, but it suggests that a paternal imprint developed either in the maternal germ line or postzygotically. We conclude (1) that the incorrect imprint in non-IC-deletion cases is the result of a spontaneous prezygotic or postzygotic error, (2) that these cases have a low recurrence risk, and (3) that the paternal imprint may be the default imprint.
Angelman Syndrome↗
Ablation of Goalpha overrides G1 restriction point control through Ras/ERK/cyclin D1-CDK activities.
We have generated stable IIC9 cell lines, Goa1 and Goa2, that overexpress full-length antisense Goalpha RNA. As shown previously, expression of antisense Goalpha RNA ablated the alpha subunit of the heterotrimeric G protein, Go, resulting in growth in the absence of mitogen. To better understand this change in IIC9 phenotype, we have characterized the signaling pathway and cell cycle events previously shown to be important in control of IIC9 G1/S phase progression. In this paper we clearly demonstrate that ablation of Goalpha results in growth, constitutively active Ras/ERK, elevated expression of cyclin D1, and constitutively active cyclin D1-CDK complexes, all in the absence of mitogen. Furthermore, these characteristics were abolished by the transient overexpression of the transducin heterotrimeric G protein alpha subunit strongly suggesting the transformation of Goalpha-ablated cells involves Gobetagamma subunits. This is the first study to implicate a heterotrimeric G protein in tumor suppression.
Animals↗
Evidence against the hypothesis that BCL-2 inhibits apoptosis through an anti-oxidant effect.
We contrasted possible protection against apoptosis afforded by either BCL-2 expression or anti-oxidant inhibitors in the same tumor target challenged by two distinct triggers of apoptosis. Exposure of L929 fibroblasts to tumor necrosis factor (TNF) or etoposide (VP-16) induced apoptotic death with similar kinetics. Enforced expression of BCL-2 significantly protected against apoptosis induced by VP-16 but had no effect against TNF-induced apoptosis. In contrast, the anti-oxidants desferrioxamine, butylated hydroxyanisol and N-acetyl cysteine all inhibited TNF-induced apoptosis in a concentration-dependent fashion. Although exposure to VP-16 resulted in a significant generation of intracellular oxyradicals, the above three anti-oxidant inhibitors had no effect on VP-16-induced apoptotic death. Interestingly, enforced expression of BCL-2 also inhibited the ability of VP-16 to generate oxy-radicals and to depress intracellular glutathione levels. These results indicate that BCL-2 can exert anti-oxidant effects but argue against the hypothesis that these effects are critical to its protection against apoptosis.
Journal Article↗
Multiple myeloma cells are protected against dexamethasone-induced apoptosis by insulin-like growth factors.
Multiple myeloma cell lines express functional receptors for insulin-like growth factors (IGFs) and several cell types that make up the bone marrow microenvironment produce these cytokines. This suggests that IGFs may play a role in survival and/or expansion of the malignant clone within the marrow in patients with multiple myeloma. We tested the effects of these growth factors on myeloma cells challenged with dexamethasone. Dye exclusion and MTT assays demonstrated that both IGF-I and IGF-II protected the 8226 and dox-40 myeloma cell lines and three primary myeloma cultures from dexamethasone-induced cytotoxicity in a dose-dependent fashion. Morphologic studies of target cells and their nuclei as well as DNA electrophoresis confirmed the IGFs afforded protection against dexamethasone-induced apoptosis. Insulin also protected but was less impressive and required much higher concentrations. IGFs also protected against cycloheximide-induced apoptosis but were ineffective against serum starvation, topoisomerase II inhibitors, or anti-fas antibodies. IGF-induced protection against dexamethasone was not associated with any alteration in quantitative or qualitative expression of BCL-2, BAX or BCL-X proteins. These data indicate that insulin-like growth factors may play a role in maintenance of the malignant clone in patients with myeloma by protecting tumour cells from apoptotic death.
Animals↗