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Biomedical subjects

J Squires

Publications and source records attributed to J Squires.

At least 19 recordsLinked to original sources

Psychological follow-up study of 5-year-old ICSI children.

BACKGROUND: The developmental outcomes of children born after ICSI are still a matter of concern. The purpose of the present study was to investigate psychological outcomes for 5-year-old children born after ICSI and compare these with outcomes for children born after spontaneous conception (SC). METHODS: Three hundred singleton children born after ICSI in Belgium, Sweden and the USA were matched by maternal age, child age and gender. Outcome measures included the Wechsler Preschool and Primary scales of intelligence (WPPSI-R), Peabody Developmental Motor Scales, Parenting Stress Index and Child Behaviour Checklist. RESULTS: Regarding cognitive development, no significant differences were found on WPPSI-R verbal and performance scales between ICSI and SC children. However, some differences were noted on subtests of the Performance Scale. ICSI children more often obtained a score below 1 SD of the mean on the subtests: Object Assembly, Block Design and Mazes (all P<0.05). Significant differences by site (i.e. Belgium, Sweden and New York) were found on subtests related to parenting stress, child behaviour problems and motor development (all P<0.05). These findings can probably be explained by variables other than conception mode, such as cultural differences and selection bias. CONCLUSIONS: Although the finding that a higher proportion of ICSI children obtained scores below the cut-off on some of the visual-spatial subscales of the WPPSI-R warrants further investigation, ICSI does not appear to affect the psychological well-being or cognitive development at age 5.

Birth Weight↗

Parent-completed developmental screening in a Norwegian population sample: a comparison with US normative data.

AIM: To compare normative data of a Norwegian translation of the Ages and Stages Questionnaires with original US normative data. METHODS: Norwegian-born mothers randomly selected from the population register completed Norwegian translations of the Ages and Stages Questionnaires, a series of 19 age-specific child development screening questionnaires each made up of 30 items in five domains: Communication, Gross Motor, Fine Motor, Problem Solving, and Personal-Social. Domain score group differences with original US normative data on 10 age-specific questionnaires (for ages 4, 8, 12, 16, 20, 24, 30, 36, 48, and 60 mo) were investigated. The Norwegian data consisted of 1341 children, varying between 82 and 176 per age interval. RESULTS: On the whole, parents' reports of their children's development were very similar in the two data sets. Only five out of 50 mean comparisons revealed a mean difference either greater than a Cohen's d of 0.5 or greater than the smallest increment on a domain score. The variation in scores tended to be somewhat smaller in the Norwegian sample. CONCLUSION: It seems reasonable to expect that domain scores on the Ages and Stages Questionnaires may be interpreted in the same way in Norway and the United States, and these results may also generalize to other Western settings. These findings from a true random sample also increase the confidence in the original normative data.

Child Development↗

Basiliximab widens the therapeutic window for AUC-monitored neoral therapy early after kidney transplantation.

Early adequate cyclosporine exposure has been shown to predict low acute rejection. Recently basiliximab induction has been added to immunosuppressive regimens to further reduce rejection. The aim of this study was to determine the importance of achieving the early cyclosporine therapeutic threshold with basiliximab induction. A retrospective analysis of first cadaver and nonidentical living donor transplant recipients treated with or without basiliximab induction was performed. All patients (n = 170) received neoral, mycophenolate mofetil, and prednisone. The cyclosporine absorption profile was measured on day 3. Adequate cyclosporine exposure was defined as area under the curve (AUC) 0-4: >4400 microg x h/L at day 3. The primary outcome was acute rejection (AR) within the first 6 month. In the no basiliximab (control) group, AR occurred in 22% (17/78) of recipients and was strongly associated with low cyclosporine exposure on day 3. AR occurred in 39% (9/23) with cyclosporine AUC0-4 < 4400 microg x h/L compared with 15% (8/55) with AUC0-4 > 4400 microg x h/L (P =.016). In the basiliximab group, AR occurred in only 9% (8/92) of recipients and did not correlate with cyclosporine exposure. AR occurred in 8% (2/24) with cyclosporine AUC0-4 < 4400 microg x h/L compared with 9% (6/68) with AUC0-4 > 4400 microg x h/L (P =.94). Achieving cyclosporine therapeutic targets by day 3 may not be required when anti-IL2 induction is used.

Antibodies, Monoclonal↗

Tacrolimus monitoring by simplified sparse sampling under the concentration time curve.

The purpose of this study was to determine which tacrolimus pharmacokinetic parameters best predicted efficacy in kidney transplantation. Blood tacrolimus levels at 0, 1, 2, 3, and 4 hours postdose were measured in 28 kidney transplants. All received tacrolimus-based triple-drug therapy with mychophenolate mofetil and prednisone. Associations between blood concentrations at each sampling time point and the area under the curve (AUC) 0-4 were measured by Pearson's correlation coefficients. Tacrolimus dosing was based on C0 not AUC. AUC and blood concentrations at each sampling time were retrospectively compared with C0 as predictor of acute rejection and nephrotoxicity. Although tacrolimus C0 correlated with AUC0-4 (r =.86), correlations were higher with C2 and C3 (r =.96 and r =.94, respectively). C0 levels were not significantly different in six patients with acute rejection and 23 patients without. There was a trend toward lower tacrolimus C3 in patients with AR than without AR (P =.06). C2 and C3 correlate better with AUC0-4 than C0. Early tacrolimus C3 levels may be a better than C0 as a predictor of efficacy.

Adult↗

Effect of interleukin-6 secreted by engineered human stromal cells on osteoclasts in human bone.

The effect of elevated human IL-6 (hIL-6) production by human bone marrow (Hu-BM) stromal cells on osteoclasts in human bone was examined. Human bone was implanted into nonobese diabetic mice with severe combined immunodeficiency (Hu-Bone-NOD/SCID mice). Immunohistochemistry of bone implants and mouse spleens (at 20 weeks), showed human CD45+ cells, B cells, and macrophages in both tissues. Thus, Hu-BM cells survive human bone transplantation and infiltrate mouse tissue. Bone implants had 75 +/- 12% (mean +/- SD) human CD45+ cells, and 9 +/- 4% mouse hematopoietic cells. A retrovirus vector containing the human IL-6 gene was used to transduce Hu-BM stromal cells (IL-6/stromal) and the PA317 cell line (IL-6/PA317). IL-6/ stromal cells (secreting, on average, 17 microg of hIL-6/10(6) cells per 24 h) were injected directly into human bone implants in Hu-Bone-NOD/SCID mice. IL-6/PA317 cells (secreting 16 microg/mL of hIL-6/10(6) cells per 24 h) were injected intraperitoneally into Hu-Bone-NOD/SCID mice. Analyses of sera from both groups of animals showed elevated levels of IL-6. However, only bone implants engrafted with IL-6/stromal cells had a statistically significant increase in osteoclast-lined mineralized trabecular bone surface (BS). Thus, a high concentration of serum hIL-6 in Hu-Bone-NOD/SCID mice alone does not increase osteoclast-lined BS in bone implants. Most importantly, it is the type of human BM cell that secretes the high levels of hIL-6 that is most critical.

Animals↗

The effects of feed intake and body fatness on progesterone metabolism in ovariectomized gilts.

We studied the effects of feed intake and fatness on metabolic clearance rate (MCR) and half-life of progesterone in 40 ovariectomized gilts (10x4 littermates). One gilt from each litter was randomly allocated to each of four treatments in a randomized block design. Gilts were reared to be either lean (Ln), 113 kg BW and 10 mm backfat measured 65 mm from the midline at the level of the last rib (P2), or fat (F), 124 kg BW and 20 mm P2 backfat. They were ovariectomized and fitted with bilateral jugular catheters. Fat and Ln gilts were then fed either low (1.15 x maintenance energy, L), or high (2.30 x maintenance energy, H) feed intakes. Gilts received an i.m. injection of 130 mg of progesterone on two consecutive days (d1 and 2). From d 3, progesterone was infused at 5.4 mg/h (130 mg/d) for 60 h. Blood samples for progesterone analysis were taken during the last 24 h of infusion and for a further 72 h. Gilts were then slaughtered, and livers were sampled for microsomal studies. Fatness did not affect any aspect of progesterone metabolism measured. Postprandial MCR was greater in H than in L gilts, 103.0 vs. 76.1 mL x min(-1) x kg BW(-1) (P<.01), respectively. Feed intake did not affect the disappearance rate constant of progesterone (mean -.019), and the estimated half-life of progesterone was 36.5 h. High-intake gilts had larger proportional liver size (P<.001) than L gilts. Microsomal metabolism of progesterone and P450 enzyme concentration were similar across treatments. We conclude that increasing feed intake increases MCR of progesterone and could be used to manipulate progesterone concentration in sows.

Adipose Tissue↗

Revision of a parent-completed development screening tool: Ages and Stages Questionnaires.

Examined the Ages and Stages Questionnaires (ASQ), a series of 11 developmental questionnaires designed to be completed by parents and caregivers of young children from 4 to 48 months of age. The ASQ were recently revised and additional psychometric data were gathered. Analyses on over 7,000 questionnaires indicated high test-retest reliability, interobserver reliability, and internal consistency. Concurrent validity using standardized measures yielded on overall agreement of 85%, with a range of 76-91%. Specificity was high across questionnaire intervals while sensitivity was lower and varied across intervals. Use of parent-completed screening tools such as the ASQ is attractive in terms of cost-effectiveness, parental involvement, and flexibility in administration procedures.

Case-Control Studies↗

Azithromycin therapy for Cryptosporidium parvum infection in four children infected with human immunodeficiency virus.

Cryptosporidium parvum intestinal infection in immunodeficient patients can cause severe intestinal fluid losses with severe dehydration or chronic diarrhea with malnutrition. Therapies tried in human beings and animals include paromomycin, clarithromycin, azithromycin, octreotide, hyperimmune bovine colostrum, and bovine transfer factor. No specific therapy has been found to be consistently beneficial to children. We report azithromycin treatment of four children with acquired immunodeficiency syndrome who had severe diarrheal illnesses in which Cryptosporidium parvum was the sole pathogen detected. Three of these children had a marked decrease in stool volume and frequency within 36 hours of initiating therapy and resolution of diarrhea within 5 days; Cryptosporidium organisms became undetectable on examination of stool or colonic biopsy or by both after therapy was discontinued. A fourth patient required prolonged therapy with azithromycin to achieve clearance. Azithromycin therapy should be considered for immunocompromised patients with intestinal Cryptosporidium infection.

AIDS-Related Opportunistic Infections↗

Heterozygosity for long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency and deterioration in liver function in a newborn infant infected with human immunodeficiency virus.

A child with perinatally acquired human immunodeficiency virus infection had rapidly progressive hepatic dysfunction, as had her older sibling who died. Urinary organic acid studies revealed 3-hydroxydicarboxylic aciduria, and cultured skin fibroblasts had reduced activity of 3-hydroxy-coenzyme A dehydrogenase. The introduction of a low fat diet resulted in marked improvement in clinical status and reversal of the liver disease. This case illustrates the necessity of metabolic evaluation in patients with liver dysfunction, even when other causes of liver dysfunction are present.

Acquired Immunodeficiency Syndrome↗

alpha-Linolenic acid- and docosahexaenoic acid-enriched eggs from hens fed flaxseed: influence on blood lipids and platelet phospholipid fatty acids in humans.

This study was undertaken to examine the effects that consumption of eggs from hens fed diets containing flaxseed would have on plasma and platelet lipids of male volunteers. Feeding diets containing 0%, 10%, and 20% ground flaxseed to Leghorn pullets provided a marked progressive increase in n-3 fatty acid content as alpha-linolenic acid (alpha-LNA) (28, 261, and 527 mg/egg) and docosahexaenoic acid (DHA) (51, 81, and 87 mg/egg) but no alteration in the cholesterol concentration of the egg yolk. Twenty-eight male volunteers, divided into three groups, were fed four eggs per day for 2 wk according to a cyclic Latin-square design. No statistically significant changes were observed in total cholesterol, high-density-lipoprotein cholesterol, or plasma triglyceride concentrations. Significant increases in total n-3 fatty acids and in DHA content (which rose from 1.5 to 2.0% by wt or 33% overall), and a significant decrease in ratio of n-6 to n-3 fatty acids were found in platelet phospholipids of subjects consuming eggs from flaxseed-fed hens. Health and Welfare Canada in 1990 set recommended intakes for dietary n-3 fatty acids and for the ratio of n-6 to n-3 fatty acids, which are not being met currently by the overall population. Eggs modified by the inclusion of flaxseed in the laying hens' diet could provide an important nutritional source of n-3 fatty acid.

Adult↗

Loracarbef vs. cefaclor in pediatric skin and skin structure infections.

A double blind, randomized clinical trial involving 214 children, ages 6 months to 12 years, compared the safety and effectiveness of the new carbacephem loracarbef and the cephalosporin cefaclor for the treatment of skin and skin structure infections. The two agents were given primarily as oral suspensions. Dosages were 15 mg/kg/day in two divided doses for loracarbef and 20 mg/kg/day in three divided doses for cefaclor. Assessment 72 hours after completion of the 7-day course of treatment indicated a favorable clinical response plus eradication of the pretherapy pathogen in 97.3% of the 74 loracarbef-treated patients eligible for evaluation and 92.3% of 78 evaluable cefaclor-treated patients. Favorable response rates at a second posttreatment visit 10 to 14 days after the end of therapy were 95.6% in 68 evaluable loracarbef-treated patients and 86.2% in 65 treated with cefaclor. The incidence of adverse reactions, including gastrointestinal effects, was low in both groups. No statistical difference in clinical or bacteriologic efficacy or safety was detected between patients treated with loracarbef and cefaclor.

Cefaclor↗

Measles: an epidemic of upper airway obstruction.

Between October 1989 and August 1990, Dallas County experienced an 11-month epidemic of measles. Of 995 cases of pediatric measles diagnosed in the outpatient department of Children's Medical Center, 108 patients were admitted and 34 of these demonstrated significant upper airway obstruction at the time of admission. Airway problems ranged from mild inspiratory stridor with nasal flaring to frank obstruction and arrest in the emergency room, requiring intubation. Eight of the 34 airway patients were eventually diagnosed with bacterial tracheitis on the basis of endoscopic findings and culture results. The remaining patients had pictures more consistent with viral laryngotracheitis, but all patients were treated with broad-spectrum antibiotics to prevent possible progression to bacterial tracheitis. A total of nine patients overall required intubation for airway obstruction and all were successfully extubated. Large outbreaks of measles are becoming common again in populations of urban poor--largely unvaccinated children. The disease in these populations tends to occur at a younger age and may be more aggressive with more associated complications. Physicians must keep in mind the possibility of upper airway obstruction in a significant proportion of these patients. Early diagnosis on the basis of clinical signs and symptoms, endoscopy, and radiographs is the key to timely appropriate management.

Adolescent↗