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Biomedical subjects

R J Smith

Publications and source records attributed to R J Smith.

At least 199 records · Page 11Linked to original sources

Suprastomal granulation tissue and pediatric tracheotomy decannulation.

Although numerous decannulation techniques have been reported, often involving costly sleep studies, repetitive laser procedures, and tracheotomy tube "downsizing," no established standard of care exists. We advocate the following simple, minimally invasive decannulation protocol. After excluding concomitant airway lesions, suprastomal granulation is removed transtomally by an endoscopically guided rongeur. A tracheotomy tube is then fashioned with a fenestration centered in the tracheal lumen. Decannulation occurs if the patient maintains adequate ventilation over a 12- to 24-hour observation period with the fenestrated tracheotomy capped. Over 18 months we prospectively followed 10 consecutive children presenting as potential decannulation candidates. Using the aforementioned technique, nine of 10 patients were successfully decannulated (average follow-up, 11.5 months). The postoperative capped fenestrated tracheotomy trial provides a realistic assessment of preparedness for decannulation. We recommend this protocol as a rapid, efficient, and cost-effective means of achieving decannulation.

Adolescent↗

A classification scheme for paradoxical vocal cord motion.

Paradoxical vocal cord motion (PVCM) is characterized by the inappropriate adduction of the true vocal cords during inspiration. Multiple causes have been proposed for this group of disorders, which share the common finding of mobile vocal cords that adduct inappropriately during inspiration and cause stridor by approximation. Management of this group of disorders has been complicated by the lack of a classification scheme to include all types of PVCM. We propose that PVCM be classified according to its underlying etiology and recognize the following causes of the disorder: 1. brainstem compression; 2. cortical or upper motor neuron injury; 3. nuclear or lower motor neuron injury; 4. movement disorder; 5. gastroesophageal reflux; 6. factitious or malingering disorder; 7. somatization/conversion disorder. Case reports are presented to illustrate the characteristic features and diagnostic evaluation used in assessing patients with PVCM. Management varies depending on the cause of PVCM and entails speech therapy, pharmacologic therapy, behavioral modification, and/or surgical intervention. Recognition of the multiple causes of PVCM allows otolaryngologists to formulate well-directed diagnostic evaluation and treatment.

Adolescent↗

Construction of P1-derived artificial chromosome and yeast artificial chromosome contigs encompassing the DFNB7 and DFNB11 region of chromosome 9q13-21.

DFNB7 and DFNB11, two loci for autosomal recessive nonsyndromic hearing loss (ARNSHL), have been mapped to chromosome 9q13-21 in separate consanguineous families. Using a radiation hybrid map, we have determined the correct marker order in the DFNB7/11 region and have demonstrated that the DFNB11 locus resides within a redefined DFNB7 interval. The gene(s) responsible for ARNSHL at these loci resides within an approximately 1 cM interval bounded by markers D9S1806 (centromeric) and D9S769 (telomeric). A recently discovered Indian family confirms the new telomeric boundary. To assist in the identification and cloning of candidate genes, YAC and PAC contigs were constructed. A total of 19 YAC and 23 PAC clones were utilized to span the affected region and ensure double coverage throughout. Twenty-two previously published STSs and 21 new STSs were used to determine marker order and confirm the integrity of the contig. Using a positional cloning strategy we have identified three cochlear expressed genes that map to the DFNB7/11 interval.

Chromosome Mapping↗

Estimating benchmark concentrations and other noncancer endpoints in epidemiology studies.

Methods for evaluating the hazards associated with noncancer responses with epidemiologic data are considered. The methods for noncancer risk assessment have largely been developed for experimental data, and are not always suitable for the more complex structure of epidemiologic data. In epidemiology, the measurement of the response and the exposure is often either continuous or dichotomous. For a continuous noncancer response modeled with multiple regression, a variety of endpoints may be examined: (1) the concentration associated with absolute or relative decrements in response; (2) a threshold concentration associated with no change in response; and (3) the concentration associated with a particular added risk of impairment. For a dichotomous noncancer response modeled with logistic regression, concentrations associated with specified added/extra risk or with a threshold responses may be estimated. No-observed-effect concentrations may also be estimated for categorizations of exposures for both continuous and dichotomous responses but these may depend on the arbitrary categories chosen. Respiratory function in miners exposed to coal dust is used to illustrate these methods.

Age Factors↗

A re-examination of risk estimates from the NIOSH Occupational Noise and Hearing Survey (ONHS)

This paper describes a new analysis of data from the 1968-72 National Institute for Occupational Safety & Health (NIOSH) Occupational Noise and Hearing Survey (ONHS). The population consisted of 1172 (792 noise-exposed and 380 "controls") predominately white male workers from a cross section of industries within the United States. The analysis focused on how risk estimates vary according to various model assumptions, including shape of the dose-response curve and the amount of noise exposure among low-noise exposed workers (or controls). Logistic regression models were used to describe the risk of hearing handicap in relation to age, occupational noise exposure, and duration exposed. Excess risk estimates were generated for several definitions of hearing handicap. Hearing handicap is usually denoted as an average hearing threshold level (HTL) of greater than 25 dB for both ears at selected frequencies. The frequencies included in the biaural averages were (1) the articulation-weighted average over 1-4 kHz, (2) the unweighted average over 0.5, 1, and 2 kHz, and (3) the unweighted average over 1, 2, and 3 kHz. The results show that excess risk estimates for time-weighted average sound levels below 85 dB were sensitive to statistical model form and assumptions regarding the sound level to which the "control" group was exposed. The choice of frequencies used in the hearing handicap definition affected the magnitude of excess risk estimates, which depended on age and duration of exposure. Although data were limited below 85 dB, an age-stratified analysis provided evidence of excess risks at levels ranging from 80 to 84 dB, 85-89 dB, and 90-102 dB. Due to uncertainty in quantifying risks below 85 dB, new data collection efforts should focus on better characterization of dose-response and longitudinal hearing surveys that include workers exposed to 8-hour time-weighted noise levels below 85 dB. Results are compared to excess risk estimates generated using methods given by ANSI S3.44-1996.

Adolescent↗

Usher's syndrome type IC: clinical studies and fine-mapping the disease locus.

Usher's syndrome type I is a heterogeneous group of diseases characterized by severe to profound sensorineural hearing loss, absent vestibular function, and progressive pigmentary retinopathy. Other identifying clinical features have not been documented. In this study, we examined olfactory acuity, plasma levels of polyunsaturated fatty acids and sarcosine, and cilia ultrastructure in a homogeneous cohort of patients with Usher's syndrome type IC. The normal age-dependent decline in olfactory acuity was observed, and normal plasma levels of polyunsaturated fatty acids and sarcosine were found. However, the incidence of compound cilia in biopsies from the inferior turbinate was significantly higher than that reported in control populations. By reconstructing haplotypes in affected persons. D11S902 and D11S1310 were identified as flanking markers over an interval that contains a candidate gene, KCNC1. No mutations in the coding sequence of this gene could be demonstrated in affected persons.

Adolescent↗

Management of congenital buccopharyngeal membrane.

OBJECTIVE: To describe our experience in treating congenital buccopharyngeal membranes and reflect on lessons learned managing this rare anomaly. DESIGN: Case series of two patients followed 3 and 6 years, respectively. SETTING: Two different academic tertiary-care medical centers. PATIENTS: Two patients with congenital buccopharyngeal membranes. INTERVENTION: Multiple pharyngoplasties, including the use of lasers, rotated mucosal flaps, and oropharyngeal stents. RESULTS: The first patient has had her tracheotomy removed, but she still uses a gastrostomy tube and has an expressive speech delay. The second patient can eat well but has persistent speech and airway problems, largely due to his micrognathia. CONCLUSIONS: Centrally dehiscent buccopharyngeal membranes are rare and require carefully planned treatment. Associated anomalies worsen the prognosis. We propose a set of recommendations to assist in the management of this difficult problem.

Airway Obstruction↗

A gene for autosomal dominant nonsyndromic hearing loss (DFNA12) maps to chromosome 11q22-24.

We performed linkage analysis in a Belgian family with autosomal dominant midfrequency hearing loss, which has a prelingual onset and a nonprogressive course in most patients. We found LOD scores >6 with markers on chromosome 11q. Analysis of key recombinants maps this deafness gene (DFNA12) to a 36-cM interval on chromosome 11q22-24, between markers D11S4120 and D11S912. The critical regions for the recessive deafness locus DFNB2 and the dominant locus DFNA11, which were previously localized to the long arm of chromosome 11, do not overlap with the candidate interval of DFNA12.

Audiometry, Pure-Tone↗

[ The family physician's sentinel function studied with reference to referrals and referral cards].

OBJECTIVE: To study the gatekeeper function of Dutch general practitioners (GPs) by investigating the relation between the referring GP, referrals, and referral cards. (In the Netherlands, it is customary that patients only see a specialist after referral by their GP. In this way the GP acts as a gatekeeper between primary and secondary care. Specialists are paid by the patient's insurance company which they send a so-called referral card stating the name of the referring GP.) DESIGN: Descriptive. SETTING: Hospitals in Groningen and Hoogeveen and four general practices in the area. METHOD: The study questions were answered using data for 1993 of the computerized morbidity Registration Network Groningen (RNG) of the Department of Family Medicine of Groningen University and data of two regional health insurance companies (RZG and Het Groene Land). RESULTS: For 1993 the RNG showed a referral-referral card ratio of 34%, ranging from 24% to 42% among different practices; and from 17-46% among the various specialties. For the surgical specialties, the range of indications for which patients were actively referred to the various specialties varied from 21-33 per 100 referrals, for the non-surgical specialties it ranged from 25 to 56 per 100 referrals. The number of referrals by the 'own' GP accounted for an average of three-quarters of the referral cards attributed to the own GP. The last five years the number of referrals varied showing no clear increase or decrease. DISCUSSION: GPs appeared to have difficulty in acting as gatekeeper once patients were being treated by the specialist. In studies of referrals. research into specialists' follow-up strategies should be an integral part. A back referral or return card could facilitate this type of study.

Adolescent↗

Chronic growth hormone treatment in normal rats reduces post-prandial skeletal muscle plasma membrane GLUT1 content, but not glucose transport or GLUT4 expression and localization.

Whether skeletal muscle glucose transport system is impaired in the basal, post-prandial state during chronic growth hormone treatment is unknown. The current study was designed to determine whether 4 weeks of human growth hormone (hGH) treatment (3.5 mg/kg per day) would impair glucose transport and/or the number of glucose transporters in plasma membrane vesicles isolated from hindlimb skeletal muscle of Sprague-Dawley rats under basal, post-prandial conditions. hGH treatment was shown to have no effect on glucose influx (Vmax or K(m)) determined under equilibrium exchange conditions in isolated plasma membrane vesicles. Plasma membrane glucose transporter number (Ro) measured by cytochalasin B binding was also unchanged by hGH treatment. Consequently, glucose transporter turnover number (Vmax/Ro), a measure of average glucose transporter intrinsic activity, was similar in hGH-treated and control rats. hGH did not change GLUT4 protein content in whole muscle or in the plasma membrane, and muscle content of GLUT4 mRNA also was unchanged. In contrast, GLUT1 protein content in the plasma membrane fraction was significantly reduced by hGH treatment. This was associated with a modest, although not significant, decrease in muscle content of GLUT1 mRNA. In conclusion, high-dose hGH treatment for 4 weeks did not alter post-prandial skeletal muscle glucose transport activity. Neither the muscle level nor the intracellular localization of GLUT4 was changed by the hormone treatment. On the contrary, the basal post-prandial level of GLUT1 in the plasma membrane was reduced by hGH. The mRNA data suggest that this reduction might result from a decrease in the synthesis of GLUT1.

Animals↗

Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus.

Grb10 is a member of a recently identified family of adapter proteins that are thought to play a role in receptor tyrosine kinase-mediated signal transduction. We identified and isolated the Grb10 SH2 domain based on its interaction with the intracellular domain of the insulin receptor beta-subunit using the yeast two-hybrid system. The interaction was specific for the insulin receptor and the insulin-like growth factor-1 receptor, and it required a catalytically active receptor kinase domain and an intact Grb10 SH2 domain. Glutathione S-transferase fusion proteins containing the Grb10 SH2 domain associated in an insulin-dependent manner with insulin receptors from cell lysates and with purified insulin receptors. Co-precipitation experiments revealed the association of cellular Grb10 with hormone-stimulated insulin receptors in cell extracts. The Grb10 SH2 domain did not bind to an insulin receptor lacking 43 amino acids at the carboxyl terminus, and it exhibited highest affinity for a phosphopeptide containing Tyr(P)-1322. Unlike p85 and Syp, which also bind to Tyr(P)-1322, Grb10 was not found to associate with insulin receptor substrate-1. These results suggest that Grb10 is a novel insulin receptor interactive protein and provide direct evidence for an insulin receptor substrate-1-independent function of the insulin receptor carboxyl terminus in protein binding.

3T3 Cells↗

OK-432 therapy for lymphangiomas.

OBJECTIVE: To assess the efficacy of OK-432 sclerotherapy in the treatment of lymphangiomas. DESIGN: Nonrandomized trial; follow-up, 4 to 29 months. SETTING: Academic tertiary referral medical center. PATIENTS: Six children with presumed lymphangiomas; age range at initial treatment, 1 month to 7 years 10 months. INTERVENTION: Fluoroscopically guided cyst aspiration, cystography, and injection of OK-432. OUTCOME MEASURES: Clinical and radiographic comparisons before and after therapy. RESULTS: Complete response in 2 macrocystic lymphangiomas; no response in 3 microcystic lymphangiomas; and no response in 1 venous malformation. CONCLUSION: OK-432 sclerotherapy may be effective treatment for macrocystic lymphangiomas.

Child↗

ICAM-1 mediates leukocyte-endothelium adhesive interactions in the reversed passive Arthus reaction.

A murine anti-rat intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody (mAb), 1A29, was used to investigate the importance of blood leukocyte-associated beta 2-integrin (CD11/CD18) vascular endothelium-associated ICAM-1 adhesive interactions in the reversed passive Arthus reaction (RPAR) in rats. An Arthus pleurisy reaction (4 h) was employed in these studies because it permits the accurate quantitation of polymorphonuclear neutrophil (PMN) influx into the pleural space and fluid accumulation. 1A29, which localized within Arthus lung lesions, caused a dose-dependent (0.5-2.0 mg/kg, i.v.) inhibition of PMN influx (19-56%) and exudate volume (9-55%) in the Arthus pleurisy reaction. P7 (2 mg/kg, i.v.), a murine anti-human P-selectin mAb used as an isotype-matched control for 1A29, did not localize at the lung lesion site and was inactive. Immunohistochemical analysis of lung tissue from 1A29-treated rats demonstrated increased granulocyte accumulation in the alveolar capillaries compared with more extensive granulocyte emigration into the lung tissue and pleural space in P7-treated rats and Arthus control rats; however, quantitative image analysis revealed increased numbers of lung granulocytes in 1A29-treated rats compared with controls. Neither ICAM-1 mRNA nor expression, assessed by immunocytochemistry, was increased above control levels in rats during the pleural Arthus reaction. Neutropenia was not observed in either 1A29- or P7-treated rats.

Animals↗

Incidence of vocal fold paralysis in infants undergoing ligation of patent ductus arteriosus.

BACKGROUND: Left-sided, iatrogenic vocal fold paralysis (IVFP) secondary to recurrent laryngeal nerve injury is a potential complication of ligation of patent ductus arteriosus (PDA). This study investigates specific risk factors associated with IVFP. METHODS: A retrospective chart review was performed for all infants 12 months of age or younger who underwent operative PDA closure at the University of Iowa from January 1, 1991, to January 1, 1994. RESULTS: Six cases of IVFP were diagnosed in 68 infants who underwent PDA ligation using clips (52.9%), suture ligatures (41.2%) or both (5.9%). Compared with infants without postoperative IVFP, infants with IVFP were smaller at birth (0.9 versus 2.3 kg; p < 0.001) and more premature (gestational age, 26.3 versus 33.8 weeks; p < 0.001), and were smaller (1.1 versus 3.4 kg; p < 0.001) and younger (31.9 versus 88.4 days; p < 0.001) at operation. Weight gain from birth to operation was significant only in infants without postoperative IVFP (p < 0.05). Although the overall incidence of IVFP in all infants undergoing PDA closure was 8.8%, five of the six cases (83.3%) of IVFP occurred in extremely low birth weight infants, ie, those weighing 1 kg or less at birth. Among the cohort of extremely low birth weight babies undergoing operation, the incidence of IVFP was 22.7%. Iatrogenic vocal fold paralysis was associated only with the use of surgical clips; however, because clips were used in 90.9% of the premature infants requiring PDA ligation, it was not possible to establish whether suture ligature is a safer technique. CONCLUSIONS: This study demonstrates that the single major risk factor for IVFP after ligation of PDA is birth weight less than 1 kg.

Birth Weight↗

Determinants of plasma concentrations of insulin-like growth factor-I and albumin and their hepatic mRNAs: the role of dietary protein content and tumor necrosis factor in malnourished rats.

Protein restriction decreases plasma concentrations of albumin and insulin-like growth factor-I (IGF-I) by reducing their hepatic mRNA levels, whereas protein restriction increases IGF-I binding protein-2 (IGFBP-2) gene expression in the liver. Tumor necrosis factor (TNF), as an inducer of the injury response, decreases plasma albumin concentration and albumin mRNA in the liver. The present study was designed to evaluate the effects of protein repletion and TNF on plasma albumin and IGF-I and their mRNAs and IGFBP-2 mRNA in the liver of protein-restricted rats. After 2 weeks of feeding a 2% casein diet, rats were assigned to four groups according to either being refed with a 2% or 20% casein diet or receiving saline or TNF by intraperitoneal injection (50 microg/kg x d) for 4 days. Plasma IGF-I and albumin were assayed. Hepatic mRNAs of IGF-I, albumin, and IGFBP-2 were determined. Protein repletion increased plasma concentrations of IGF-I and albumin and their mRNA content in the liver, but decreased IGFBP-2 mRNA. TNF did not alter plasma IGF-I concentration but did increase hepatic IGF-I mRNA in protein-repleted animals, and plasma albumin concentration was significantly decreased with unaltered hepatic albumin mRNA. Thus, protein repletion of malnourished rats increased plasma IGF-I and albumin concentrations in association with increased expression of their mRNAs in the liver. However, plasma albumin but not IGF-I decreased following TNF in protein-restricted rats, whereas TNF increased hepatic IGF-I mRNA in protein-repleted rats. Thus, only plasma albumin concentration responds to both principal determinants, diet and injury, in the development of malnutrition.

Animals↗

Recurrent respiratory papillomatosis.

Juvenile-onset recurrent respiratory papillomatosis is a vertically transmitted disease caused by members of the human papilloma virus family. Characterized by the relentless growth of papillomatous lesions of the larynx, recurrent respiratory papillomatosis imposes significant morbidity on patients and strain on their families. Surgical excision of the papillomata remains the mainstay of therapy, but human papilloma virus DNA persists in adjacent, normal-appearing mucosa and likely serves as a reservoir for viral reseeding. Despite multiple adjuvant treatment modalities, a cure for recurrent respiratory papillomatosis remains elusive. Most afflicted patients eventually enter spontaneous remission, but some endure several hundred surgical procedures before this welcome respite.

Adult↗

Vocal fold paralysis in infants twelve months of age and younger.

Seventeen cases of unilateral or bilateral vocal fold paralysis were diagnosed in infants younger than 12 months from 1991 to 1994 at the University of Iowa Hospitals and Clinics. Eight (47%) children with left vocal fold paralysis had a history of prior thoracic surgery--two to repair complex congenital anomalies and six to ligate a patent ductus arteriosus. During the study period, a total of 81 patent ductus arteriosus ligations were performed, yielding a 7.4% postoperative incidence of vocal fold paralysis. Seven (41%) children had idiopathic vocal fold paralysis (3 right, 1 left, 3 bilateral). Two (12%) children had VFP caused by central nervous system pathology (1 right, 1 bilateral). Tracheotomy was not required in any case. Prognosis for vocal fold paralysis varied with cause. With left vocal fold paralysis caused by thoracic surgery, no improvement was noted after an average follow-up of 6 months; with idiopathic vocal fold paralysis infants improved within an average of 6 weeks of diagnosis; with vocal fold paralysis caused by central nervous system pathology, treatment of the underlying condition was followed by return of vocal cord function. Irrespective of cause, the morbidity associated with vocal fold paralysis is minimal. Although tracheotomy is not required, careful airway observation is important. Differences and similarities of these results with other studies are discussed.

Ductus Arteriosus, Patent↗