Biomedical subjects
J Squires
Publications and source records attributed to J Squires.
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.
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.
Abuse detection in the dental environment.
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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.
Genital papillomavirus infection: clinical progression after varicella infection.
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Doctors' vs patients' clinical assessments: they don't agree!
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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.
Early detection of developmental problems: strategies for monitoring young children in the practice setting.
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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.
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.
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.
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.
Obstructive disordered breathing during sleep in patients with spinal cord injury.
Little is known about respiration and sleep in spinal cord injured (SCI) patients, and yet they frequently have complaints related to sleep. Four SCI patients with various sleep complaints were evaluated with nocturnal polysomnography. All 4 had evidence of obstructive sleep apnea (disordered breathing). These findings suggest that obstructive sleep apnea may be contributing to disruptive sleep in SCI patients and may be responsible for many of their daytime symptoms.
Control of immediate postoperative pain with topical bupivacaine hydrochloride for laparoscopic Falope ring tubal ligation.
Conflicting reports exist in the literature on the effectiveness of topical local anesthetic applied to the serosal surface of the fallopian tubes for the control of immediate postoperative pain after mechanical (band or clip) tubal ligation. Sixty-four patients were studied prospectively during outpatient laparoscopic Falope ring tubal ligation using the modified McGill Present Pain Intensity Scale. Patients randomly assigned to four groups received topical bupivacaine hydrochloride on both fallopian tubes, the right tube only, or the left tube only, or received none (controls). A unique study design was incorporated which allowed the untreated fallopian tube to serve as a within-subject control for each patient receiving unilateral treatment. Statistical analysis confirmed significant benefit when both fallopian tubes were treated as compared with no treatment (P less than .05). There was also consistent evidence of decreased immediate postoperative pain perception on the treated side for patients receiving unilateral treatment. The value of topical bupivacaine was demonstrated by both subjective patient response (McGill Pain Scale) and reduced need for pain medication before outpatient discharge. Our data support the value of topical bupivacaine applied to the serosal surface of the fallopian tubes for the reduction of postoperative pain after outpatient laparoscopic mechanical (band or clip) tubal ligation.
Bronchocentric granulomatosis in a nonasthmatic adolescent.
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The validity, reliability, and cost of a parent-completed questionnaire system to evaluate at-risk infants.
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