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Biomedical subjects

E A Smith

Publications and source records attributed to E A Smith.

At least 55 records · Page 3Linked to original sources
PubMed1997

Current urologic management of cloacal exstrophy: experience with 11 patients.

PURPOSE: Since 1980 the authors have treated 12 infants with cloacal exstrophy (10 classical and 2 variants). Eleven patients had repair, and are all surviving. The initial phases of management that led to improved survival have previously been reported. Quality of life is now a major focus for the cloacal exstrophy patient. During the past 10 years, nine of the 11 patients had lower urinary tract reconstructive procedures. This review evaluates experience with reconstructive efforts to achieve bowel and bladder control and to improve the quality of life in this complex group of patients. METHODS: Through review of patient charts and by patient interviews, data were collected to evaluate the ability to provide urinary and bowel control. A continence score was applied to provide a measure of success: voluntary control, 3; control with an enema program or intermittent catheterization, 2; incontinence with a well-functioning stoma, 1; and incontinence without a stoma, 0. The best continence score is 6 (genitourinary and gastrointestinal). Surgical complications, urodynamic and metabolic sequelae of continent urinary diversion were reviewed. RESULTS: At the time of the authors' previous report, eight of 11 patients had a continence score of 2 or less. Currently, eight of 11 patients have a score of 3 or better (five with enteric stoma and continent urinary diversion, two with enema program and continent urinary diversion, and one with enema program and continent bladder). Urinary-diversion procedures have included two gastric augmentations and five gastric reservoirs, two of which have required subsequent bowel augmentation. Gastric augmentations carry a definite risk of metabolic problems with three of our patients demonstrating significant episodes of metabolic alkalosis. In addition, results of urodynamic monitoring suggests that gastric reservoirs may be less compliant than reservoirs formed using other bowel segments. CONCLUSIONS: Modern principles of continent urinary diversion have been successfully applied to the cloacal exstrophy patient further improving their quality of life. Use of gastric flaps with preservation of intestinal length has been central to urologic reconstructive efforts. Use of stomach alone for formation of urinary reservoirs may produce suboptimal compliance, and composite ileogastric construction should be considered if the gastric flap is of marginal size.

Bladder Exstrophy↗
PubMed1997

Reassessment of germline heavy chain transcripts from two murine VH families.

While expression of functional heavy chain immunoglobulin mRNA requires rearrangement of variable (VH), diversity (D) and (JH) gene segments, these individual gene segments can be transcribed prior to their rearrangement. It has been proposed that the resulting germline, or sterile, transcripts play an important role in the rearrangement process because strong correlations between rearrangement frequency and sterile transcript levels have been observed in some studies. Murine VH genes have been grouped into families on the basis of coding sequence homology. VH families rearrange in a developmentally regulated manner, so that rearrangements of genes from several VH families are detected earlier than rearrangements of J558 family genes. Paradoxically, the only VH family for which sterile transcripts have been documented is the J558 family. We used RT-PCR analyses to ask whether sterile transcripts from other VH families could be detected in fetal liver samples prior to their rearrangement. While J558 family germline transcripts were easily detected, no sterile transcripts were observed from the S107 family. Our studies also revealed the ability of small quantities of degraded genomic DNA to nonspecifically prime cDNA synthesis, emphasizing the need for caution in interpreting RT-PCR data in which family-specific oligos are used for cDNA production. These results cast doubt on the idea that sterile transcripts are required for V(H)DJ(H) rearrangement.

Animals↗
PubMed1997

Testing for interaction between maternal smoking and TGFA genotype among oral cleft cases born in Maryland 1992-1996.

OBJECTIVE: Infants born in Maryland between June 1992 and June 1996 were used in a case-control study of nonsyndromic oral clefts to test for effects of maternal smoking and a polymorphic genetic marker at the transforming growth factor alpha (TGFA) locus, both of which have been reported to be risk factors for these common birth defects. DESIGN AND SETTING: Cases were infants with an oral cleft ascertained through three comprehensive treatment centers, with additional ascertainment through a registry of birth defects maintained by the Maryland Health Department. Controls were healthy infants. Medical history information on infants and mothers were collected, along with DNA samples. PATIENTS, PARTICIPANTS: Among 286 cases contacted (72% ascertainment), there were 192 nonsyndromic isolated oral clefts (106 M; 86 F) available for this case-control study. MAIN OUTCOME MEASURES: The largest group of 149 Caucasian nonsyndromic cases and 86 controls was used to test for association with maternal smoking and genotype at the Taq1 polymorphism in TGFA. RESULTS: While this modest sample had limited statistical power to detect gene-environment interaction, there was a significant marginal increase in risk of having an oral cleft if the mother smoked (odds ratio = 1.75, 95% CI = 1.01 to 3.02). We could not demonstrate statistical interaction between maternal smoking and TGFA genotype in this study, however, and the observed increase in the C2 allele among cases was not statistically significant. CONCLUSIONS: We could not confirm either the reported association between oral clefts and TGFA genotype or its interaction with maternal smoking. However, these data do show an increased risk if the mother smoked during pregnancy, and this effect was greatest among infants with a bilateral cleft and no close family history of clefts.

Alleles↗
PubMed1997

Basic fibroblast growth factor inhibits basal and transforming growth factor-beta induced collagen alpha 2(I) gene expression in scleroderma and normal fibroblasts.

OBJECTIVE: Studies have shown that scleroderma (systemic sclerosis, SSc) and normal fibroblasts respond differently to basic fibroblast growth factor (bFGF), SSc fibroblasts being less responsive than normal fibroblasts in mitogenic assays in vitro, bFGF also stimulates the expression of platelet derived growth factor-alpha (PDGF-alpha) receptors in normal fibroblasts, but not in SSc fibroblasts. Conversely, transforming growth factor-beta (TGF-beta) stimulates PDGF-alpha receptor expression in SSc fibroblasts, but not in normal fibroblasts. Since bFGF has been shown to inhibit collagen gene expression in several cell types, we examined responses of SSc and normal fibroblasts to bFGF alone and in combination with TGF-beta with regard to collagen alpha 2(I) (COL1A2) expression. METHODS: Fibroblasts were obtained by skin biopsy from affected areas of patients with diffuse cutaneous SSc and from healthy donors and propagated in vitro. The effects of bFGF and TGF-beta on the COL1A2 mRNA expression levels in SSc and healthy fibroblasts were analyzed by Northern blot. The effects of bFGF on the COL1A2 promoter activities in both cell types were analyzed by transient transfection assays. The effects of bFGF and TGF-beta on collagen protein synthesis were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography. RESULTS: While bFGF diminished COL1A2 mRNA in both SSc and normal cells, COL1A2 mRNA quantities in the SSc fibroblasts were not depressed to the levels expressed by normal controls. As anticipated, TGF-beta strongly induced COL1A2 mRNA levels in normal fibroblasts, and to a lesser degree in SSc fibroblasts. When cells were incubated with both TGF-beta and bFGF, the stimulatory effect of TGF-beta was completely suppressed in both cell types. bFGF decreased COL1A2 promoter activity in both cell types, suggesting that COL1A2 inhibition by bFGF occurs at least partially at the transcriptional level. The effects of bFGF and TGF-beta on the collagen protein synthesis correlated well with mRNA data, in that TGF-beta stimulated, while bFGF strongly inhibited, collagen synthesis. CONCLUSION: bFGF is a potent inhibitor of basal and TGF-beta stimulated collagen expression in human fibroblasts, and this effect is not different between SSc and healthy fibroblasts.

Collagen↗
PubMed1996

Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis.

OBJECTIVE: To determine the frequency, clinical associations, and any major histocompatibility complex correlations of antifibrillarin antibodies in patients with systemic sclerosis (SSc). METHODS: Antifibrillarin antibodies were determined by indirect immunofluorescence, immunoblotting, and immunoprecipitation, and HLA class II alleles by DNA oligotyping, in a large cohort of SSc patients. RESULTS: Antifibrillarin was found in 8% of 335 SSc sera and was significantly more common in blacks (16%) than whites (5%), in males (33%) than females (14%), and in patients with cardiac, renal, or gut involvement. The HLA class II haplotype DRB1*1302, DQB1*0604 was found significantly more frequently in SSc patients with antifibrillarin compared with race-matched normal controls and 260 SSc patients without antifibrillarin. In addition, 1 or more of the HLA-DQB1 alleles *0604, *0301, *0602, and/or *0302 was found in all antifibrillarin-positive patients, and 62% of the antifibrillarin-positive patients had 2 of these HLA-DQB1 alleles, a highly significant difference from both race-matched normal controls and antifibrillarin-negative SSc patients. CONCLUSION: Antifibrillarin, although an infrequent nucleolar autoantibody, is a marker for severe SSc, especially in blacks and males, and is strongly associated with a unique HLA haplotype, as well as with combinations of certain HLA-DQB1 alleles.

Alleles↗
PubMed1996

Bone mineral mass consolidation in young British adults.

Forty males and 40 females, ages 18-21 years, were recruited into a prospective study to investigate the consolidation of bone mineral after cessation of linear growth and the influences of calcium intake, lifestyle factors, physical activity, and body composition on bone. Three sets of bone measurements were made annually at the spine, hip, and whole body (dual-energy X-ray absorptiometry) and at the wrist and midshaft radius (single photon absorptiometry). At baseline, the bone mineral content (BMC) was significantly greater in males than females at all sites (p < 0.004). After adjustment for scan area (BA), height, weight, and age, male BMC was significantly greater than female BMC at the midshaft radius (+7.4%; p < 0.01) but lower at the spine (-10.9%; p < 0.001) with no difference at the wrist, hip, or whole body. Positive effects of leanness on bone were observed in females but not in males. Dietary calcium, nutrient intakes, and physical activity levels were not size-independent determinants of BMC at any site. Significant increases in whole-body BMC were observed within individuals over the study period of 670 (SD 51) days, +1.3% in males and +2.1% in females (p < 0.01), mirrored by increases in BMC and BA at most skeletal sites. After allowing for changes in BA, significant increases (p < 0.01) were observed in adjusted BMC for the whole body (males, +1.1%; females, +0.6%), lumbar spine (males, +1.5%; females, +1.1%), and midshaft radius (males, +1.9%; females, +2.0%). No lifestyle or anthropometric factors were identified that influenced these longitudinal increases in bone mineral.

Adolescent↗
PubMed1996

Environmental degradation of polyacrylamides. 1. Effects of artificial environmental conditions: temperature, light, and pH.

A polyacrylamide thickening agent (PATA) was formulated at four concentrations in distilled-deionized water, without and with a glyphosate-surfactant herbicide (GH). Over a 6-week period, these mixtures were exposed to various controlled temperature and light conditions. Acrylamide concentration, ammonium concentration, and pH were measured at weekly intervals to assess the degradation of polyacrylamide and acrylamide. Satellite studies were conducted to examine the effect of altered pH on solutions of PATA (i.e., does pH promote polyacrylamide depolymerization?) and GH binding to amine groups (i.e., protection from degradation). The results of these studies suggest that polyacrylamide can degrade to acrylamide by thermal and photolytic effects, that changes in pH do not promote the depolymerization of polyacrylamide, and that GH does protect polyacrylamide and acrylamide from environmental degradation. Statistically there was no linear correlation between the various parameters measured.

Acrylamide↗
PubMed1996

Submucosal bladder neck injection of bovine dermal collagen for stress urinary incontinence in the pediatric population.

PURPOSE: The surgical management of stress urinary incontinence in the pediatric population includes various surgical techniques of which the simplest is outpatient transurethral or periurethral injection of a bulking agent. Currently purified bovine dermal collagen cross-linked with glutaraldehyde (Contigen) is the only Food and Drug Administration approved bulking agent available. Patients with stable detrusor function are ideal candidates. We review our initial experience with children. MATERIALS AND METHODS: Between January 1994 and June 1995, 23 boys and 9 girls 4 to 17 years old (mean age 9) consecutively underwent submucosal bladder neck injection with cross-linked bovine dermal collagen. Incontinence was secondary to spinal dysraphism in 24 patients, complete epispadias in 4, classic bladder exstrophy in 3 and neurogenic bladder secondary to a sacral teratoma in 1. Preoperative video urodynamics documented intrinsic sphincteric deficiency in all patients with leak point pressure of 15 to 60 cm. water (mean 37). Injection volumes ranged from 2.5 to 17 cc (mean 10). Continence results were defined as dry-requiring no protection while on a 4-hour clean intermittent catheterization program, good-improved but requiring 1 to 5 pads daily and failure-no postoperative improvement or still requiring diapers. RESULTS: Of the children with neurogenic bladder 20% became dry following the first injection and an additional 28% had a good result. Furthermore, of the 6 children with exstrophy or epispadias who underwent a Young-Dees-Leadbetter procedure 50% were dry and 17% had a good result after the first injection. Complications were limited to a febrile urinary tract infection associated with urinary retention in 1 patient and transiently worse continence in 2. CONCLUSIONS: Despite the limited success rate, we believe that transurethral collagen injection therapy has a viable role in the treatment of intrinsic sphincteric deficiency in select pediatric patients, particularly since the procedure has low morbidity and can be performed on an outpatient basis. Preoperative counseling should be given with realistic expectations.

Administration, Intravesical↗
PubMed1996

Outcome of sling cystourethropexy in the pediatric population: a critical review.

PURPOSE: We performed a critical retrospective analysis of the records of all consecutive children who underwent sling cystourethropexy at our institutions. We particularly assessed the incidence and outcome in children who underwent enterocystoplasty in addition to a sling procedure. MATERIALS AND METHODS: Between May 1992 and August 1994, 24 girls and 15 boys 4 to 17 years old (mean age 9) consecutively underwent 1 of 4 techniques of sling cystourethropexy for stress urinary incontinence using rectus fascia via an abdominal approach. Diagnoses included spinal dysraphism in 34 patients, spinal trauma in 2, cecoureterocele in 1, epispadias in 1 and classic bladder exstrophy in 1. All children underwent preoperative video urodynamics. In 4 patients only a sling procedure was performed (group 1), while in 9 others a sling procedure was performed after enterocystoplasty (group 2). In 26 patients a sling procedure and concomitant enterocystoplasty were performed (group 3). RESULTS: Patients who underwent concomitant enterocystoplasty had more hyperactive preoperative urodynamics than those who did not. Postoperative continence was subcategorized in terms of patient age, sex, diagnosis (neurogenic versus nonneurogenic), preoperative video-urodynamics, surgeon technique, group (that is with or without cystoplasty) and type of enterocystoplasty (that is stomach versus ileum). Of these factors only concomitant enterocystoplasty was predictive of postoperative dry continence (73% of group 3, 33% of group 2 and 25% of group 1). In most patients who were not dry postoperative video urodynamics suggested suboptimal outlet resistance overcome by a hyperactive detrusor. No patient had postoperative upper tract deterioration. CONCLUSIONS: These results suggest that concomitant enterocystoplasty should be critically considered for pediatric patients undergoing sling cystourethropexy.

Adolescent↗
PubMed1996

Enumeration of human colonic bacteria producing phenolic and indolic compounds: effects of pH, carbohydrate availability and retention time on dissimilatory aromatic amino acid metabolism.

Concentrations of phenolic compounds in human gut contents were more than fourfold higher in the distal colon (6.2 mmol kg-1) compared to the proximal bowel (1.4 mmol kg-1). Tryptophan metabolites were never found in more than trace amounts in large intestinal contents and phenol substituted fatty acids were the major products of aromatic amino acid fermentation that accumulated in the proximal colon, whereas phenol and p-cresol were more important in the distal gut, accounting for 70% of all products of dissimilatory aromatic amino acid metabolism. In vitro incubations of colonic material showed that phenol was produced most rapidly (1.0 mumol g-1 h-1), whereas indole was formed comparatively slowly (0.06 mumol g-1 h-1). Most probable number (MPN) estimations demonstrated that large populations of phenol and indole producing bacteria occur in the large intestine (range log10 9.8-11.5 (g dry wt faeces)-1, mean 10.6, N = 7). With respect to phenolic compounds, phenylacetate and phenylpropionate producers predominated, while indoleacetate-forming bacteria were the major tryptophan-utilizing organisms. Quantitation of products of dissimilatory aromatic amino acid metabolism in MPN tubes showed that phenol and phenylpropionate mainly accumulated at low sample dilutions, whereas phenylacetate, p-cresol, indoleacetate and indolepropionate were formed in greatest amounts at high sample dilutions. The significance of pH and carbohydrate availability with respect to aromatic amino acid metabolism was shown in batch culture fermentation studies, where net production of phenolic compounds by mixed populations of intestinal bacteria was reduced by approximately 33% during growth at pH 5.5 compared to pH 6.8, and by 60% in the presence of a fermentable carbohydrate. Experiments with 16 species of intestinal bacteria belonging to six different genera showed that environmental factors such as low pH and high carbohydrate availability markedly reduced dissimilatory aromatic amino acid metabolism in some organisms, but stimulated this process in others. A three-stage continuous culture model of the colon was used to investigate the effect of system retention time (27.1 or 66.7 h) on aromatic amino acid fermentation. Qualitative and quantitative increases in phenol production occurred from vessel 1 to vessel 3 in this model. Concentrations of phenolic compounds in vessel 3 were three times greater at R = 66.7 h compared to R = 27.1 h. Phenol and p-cresol were not detected in vessel 1, though formation of these metabolites increased from vessel 2 to vessel 3, in a pattern similar to that observed in the distal colon.

Amino Acids↗
PubMed1996

Interhospital transfer of the critically ill trauma patient: the potential role of a specialist transport team in a trauma system.

A specialist transfer team based in the regional intensive therapy unit (ITU) at the Western Infirmary, Glasgow, acts as a central interhospital retrieval team for Glasgow and the west of Scotland. The establishment of trauma systems has been proposed. This paper describes the activities of the specialist transfer team to illustrate the potential role of a central retrieval team within such a system.

Adolescent↗
PubMed1996

A multicenter trial of recombinant human interferon gamma in patients with systemic sclerosis: effects on cutaneous fibrosis and interleukin 2 receptor levels.

OBJECTIVE: To evaluate the acute toxicity, potential efficacy, and effects on the soluble interleukin 2 receptor (sIL-2R) of recombinant human interferon gamma (rIFN-gamma) in patients with systemic sclerosis (SSc). METHODS: A multicentered, pilot clinical trial of rIFN-gamma was performed on 20 patients (15 women, 5 men, mean age 45 years) with active cutaneous SSc (mean disease duration 36 months) to evaluate it potential as a novel therapy for this untreatable disorder. After one week of rIFN-gamma 0.01 mg/m2/day, subjects self-administered rIFN-gamma 0.1 mg/m2/day intramuscularly for a total of 18 weeks. The major outcome variable was a modified skin score (0 = normal skin, 3 = hidebound skin) measured and summed from 15 anatomic areas of the body. sIL-2R levels were measured by ELISA at entry and exit from the study. RESULTS: The clinical results were modest at best. Nine of 20 patients achieved at least a 20% reduction in skin score, with one patient showing almost total remission of all skin abnormalities. The mean skin score at entry for all subjects was 22.8 +/- 8.9 and over the course of the trial improved marginally compared to baseline (mean change -4.72 +/- 6.62; p = 0.008). However, 8 subjects did not change appreciably while in the trial. Antibodies to Scl-70 were observed in only 5 patients (all with diffuse scleroderma) and were not associated with either response to or complications from therapy. The adverse reactions were frequent and occasionally severe. Ten subjects were withdrawn because of exacerbation of Raynaud's symptoms (n = 5), constitutional symptoms (n = 2), development of renal crises (n = 2), and mild pancytopenia (n = 1). Minor laboratory abnormalities were common and included elevation of cholesterol, triglycerides, hepatic transaminases, and reduction in white blood cell count. Compared to controls, mean sIL-2R was markedly elevated at entry (1309 +/- 495 U/ml; p = 0.0001) and did not change appreciably at exit. Spearman correlation analysis showed a trend but no statistically significant association of skin score with sIL-2R (R = 0.408; p = 0.074). However, sIL-2R was significantly correlated with erythrocyte sedimentation rate (R = 0.542; p = 0.0165). A subset analysis revealed that skin score (p = 0.0001) and sIL-2R (p = 0.00170) were significantly higher at baseline for patients with diffuse scleroderma compared to patients with limited disease. CONCLUSION: rIFN-gamma may be beneficial for some patients with SSc, but the benefit appears marginal for most individuals and the side effects frequent. Although sIL-2R was elevated in many of the patients with SSc, it did not appear to be correlated with activity of cutaneous disease or response to therapy.

Adult↗
PubMed1995

Transfer of the critically ill obstetric patient: experience of a specialist team and guidelines for the non-specialist.

Transfer of the critically ill obstetric patient between hospitals is increasingly common. The specialist transfer team based at the Western Infirmary Intensive Therapy Unit, Glasgow has transported 60 such patients in the years 1985-1994. Monitoring was by direct arterial pressure measurement in 56 patients and central venous pressure measurement in 45. Forty-one patients were mechanically ventilated in transit. There were no deaths in transit but 3 patients died later in intensive care. The majority of patients had pregnancy induced hypertension or had suffered a post partum haemorrhage. A clinical impression that these two groups had different treatment requirements and outcomes was not substantiated. We conclude that the transfer of even the sickest obstetric patient is feasible and safe and suggest guidelines to non-specialists for the management of these patients before and during interhospital transfer.

Journal Article↗
PubMed1995

A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia.

Hypochondroplasia (MIM 146000) is an autosomal dominant skeletal dysplasia with skeletal features similar to but milder than those seen in achondroplasia. Within the past year, the achondroplasia locus has been mapped to 4p 16.3 (refs 5-7) and mutations in the fibroblast growth factor receptor 3 (FGFR3) gene have been identified in patients with the disorder. More than 95% of 242 cases reported so far are accounted for by a single Gly380Arg mutation. McKusick et al. proposed that achondroplasia and hypochondroplasia are allelic based on the similarities in phenotype between the two disorders and the identification of a severely dwarfed individual whose father had achondroplasia and whose mother had hypochondroplasia. There is also genetic linkage evidence that hypochondroplasia and achondroplasia map to the same locus. We therefore began a systematic screening of FGFR3 to detect mutations in patients with hypochondroplasia. We now report a single FGFR3 mutation found in 8 out of 14 unrelated patients with hypochondroplasia. This mutation causes a C to A transversion at nucleotide 1620, resulting in an Asn540Lys substitution in the proximal tyrosine kinase domain.

Achondroplasia↗
PubMed1995

Pasteurella multocida tonsillitis: case report and review.

Pasteurella multocida is frequently part of the normal flora of the nasopharynx and digestive tract of several wild and domestic animals. Although P. multocida can produce a variety of upper and lower respiratory tract infections, only four previous cases of tonsillitis caused by this organism have been reported. We present a case of pasteurella tonsillitis in a 30-year-old female who was exposed through her cat, which manifested upper respiratory symptoms.

Adult↗