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Biomedical subjects

M J Cunningham

Publications and source records attributed to M J Cunningham.

At least 19 recordsLinked to original sources
PubMed2000

Impact of tympanostomy tubes on child quality of life.

BACKGROUND: The objective benefits of tympanostomy tubes for otitis media are well established, but the subjective impact of surgery on child quality of life (QOL) has not been systematically studied. OBJECTIVES: To determine the subjective impact of tympanostomy tubes on child QOL, and to compare the variability in QOL before surgery with that observed after surgery. DESIGN: Prospective, observational, before-and-after trial. SETTING: Fourteen referral-based pediatric otolaryngology practices in the United States. PATIENTS: Consecutive (64%) and convenience (36%) sample of 248 children (median age, 1.4 years) with otitis media scheduled for bilateral tympanostomy tube placement as an isolated surgical procedure. INTERVENTION: Tympanostomy tubes were inserted as part of routine clinical care. Validated measures of QOL (OM-6 survey), satisfaction with health care decision (Satisfaction With Decision Scale), and satisfaction with office visit; surveys were completed at baseline (visit 1), at surgery (visit 2), and after surgery (visit 3). MAIN OUTCOME MEASURES: Short-term changes in QOL before surgery (visit 1 to visit 2) and after surgery (visit 2 to visit 3). RESULTS: Changes in QOL before surgery were mostly trivial, and were smaller than changes observed after surgery (P<.001). Large, moderate, and small improvements in QOL occurred after surgery in 56%, 15%, and 8% of children, respectively. Physical symptoms, caregiver concerns, emotional distress, and hearing loss were most improved, but significant changes were also seen for activity limitations and speech impairment. Trivial changes occurred in 17% of children, and 4% had poorer QOL. Predictors of poorer QOL were otorrhea 3 or more days (10% of variance) and decreased satisfaction with surgical decision (3% of variance). Hearing status, child age, type of otitis media (recurrent vs chronic), and office visit satisfaction were unrelated to outcome. CONCLUSIONS: Tympanostomy tubes produce large short-term improvements in QOL for most children. The best outcomes occur when postoperative otorrhea is absent or minimal, and when parents are satisfied with their initial decision to have surgery. Further research is needed to document the long-term impact of tubes on child QOL.

Child↗
PubMed2000

The application of shannon entropy in the identification of putative drug targets.

A major challenge in the field of functional genomics is the development of computational techniques for organizing and interpreting large amounts of gene expression data. These methods will be critical for the discovery of new therapeutic drug targets. Here, we present a simple method for determining the most likely drug target candidates from temporal gene expression patterns assayed with reverse-transcription polymerase chain reaction (RT-PCR) and DNA microarrays.

Animals↗
PubMed2000

Physician experience with an optical image guidance system for sinus surgery.

OBJECTIVES/HYPOTHESIS: Intraoperative guidance systems have been developed which use infrared tracking technology to assist with anatomical localization during sinus surgery. Although the introduction of this technology is intended to increase the safety and efficacy of sinus surgery, little is known about its actual impact in the clinical setting. The objective of this report was to study the application and utilization of an image guidance system shared by multiple sinus surgeons in a specialty hospital. STUDY DESIGN: Combined prospective case study and retrospective analysis of physician surveys. METHODS: An optical-based image guidance system (LandmarX, Xomed, Inc., Jacksonville, FL) was used by 34 physicians to perform 754 sinonasal surgeries over a 2.5-year period at Massachusetts Eye and Ear Infirmary. In 19 cases, system registration was repeated during surgery to measure the effect of fiducial placement on system accuracy. RESULTS: The measured accuracy of anatomical localization at the start of surgery (mean value, 1.69 +/- 0.38 mm) was comparable to the perceived accuracy of 1 to 3 mm that was reported by 79% of surgeons surveyed. Operating room time (mean period, 130.6 +/- 41.1 min) correlated with the surgical procedure performed (P < .05), but not with the disease stage or revision rate. According to a majority of surgeons, use of the image guidance equipment increased operating room time by 15 to 30 minutes during initial cases and by 5 to 15 minutes once experience with the equipment had been acquired. More than 90% of surgeons anticipated their continued use of the image guidance equipment for sinus surgery at a similar or greater level in the future. CONCLUSION: An optical-based image guidance system can be successfully integrated into a multisurgeon operating room environment. Use of the system provides accurate anatomical localization during sinus surgery and results in a relatively high level of physician satisfaction.

Adolescent↗
PubMed2000

Galanin's functional significance in the regulation of the neuroendocrine reproductive axis of the monkey.

Galanin stimulates the neuroendocrine reproductive axis in the rat, but whether galanin acts similarly in primate species is unknown. To test the hypothesis that galanin acts within the hypothalamo-hypophyseal axis to stimulate luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) secretion in the primate, galanin was administered either systemically or directly into the arcuate nucleus-median eminence of ovariectomized macaques (pigtailed or rhesus, respectively) that were maintained on estradiol. The mean plasma levels of LH were significantly elevated in pigtailed macaques after peripheral injection of galanin (2 mg) as compared with vehicle treatment. In rhesus monkeys, galanin (80 microM) administered by push-pull perfusion into the arcuate nucleus-median eminence did not significantly alter either GnRH or LH release. To determine whether in the monkey, as in the rat, subpopulations of medial forebrain GnRH neurons coexpress galanin mRNA, we used single- and double-label in situ hybridization and computerized imaging techniques. GnRH mRNA-containing cells were identified in both the medial and lateral forebrain of the female pigtailed macaque. No galanin mRNA expression was detectable in GnRH neurons located in either the medial preoptic area or mediobasal hypothalamus; however, within the substantia innominata a subset of GnRH mRNA-expressing neurons did coexpress galanin mRNA. Taken together, these results suggest that galanin induces LH release in primates, but galanin may not act directly on hypothalamic GnRH neurons. Presently, we have confirmed in another primate species the existence of GnRH gene expression in the lateral forebrain and discovered that a small subset of these neurons coexpress galanin. These particular cells may have a unique and as of yet undefined physiological function that is distinct from those GnRH neurons serving a hypophysiotropic function.

Animals↗
PubMed2000

Galanin-like peptide (GALP) is a target for regulation by leptin in the hypothalamus of the rat.

Galanin-like peptide (GALP), which was recently isolated from the porcine hypothalamus, shares sequence homology with galanin and binds with high affinity to galanin receptors. To study the distribution and regulation of GALP-expressing cells in the brain, we cloned a 120 base-pair cDNA fragment of rat GALP and produced an antisense riboprobe. In situ hybridization for GALP mRNA was then performed on tissue sections throughout the forebrain of adult ovariectomized female rats. We found GALP mRNA-containing cells in the arcuate nucleus (Arc), caudal dorsomedial nucleus, median eminence and the pituitary. Because GALP mRNA in the Arc appeared to overlap with the known distribution of leptin receptor mRNA, we tested the hypothesis that GALP expression is regulated by leptin. Using in situ hybridization, we compared the number of GALP mRNA-containing cells among groups of rats that were fed ad lib or fasted for 48 h and treated with either leptin or vehicle. Fasting reduced the number of identifiable cells containing GALP mRNA in the Arc, whereas the treatment of fasted animals with leptin produced a 4-fold increase in the number of cells expressing GALP message. The presence of GALP mRNA in the hypothalamus and pituitary and its regulation by leptin suggests that GALP may have important neuroendocrine functions, including the physiological regulation of feeding, metabolism, and reproduction.

Animals↗
PubMed1999

Rigid tracheobronchoscopy-induced bacteremia in the pediatric population.

OBJECTIVE: To assess the incidence of bacteremia following rigid tracheobronchoscopy in children to determine whether use of prophylactic antibiotics is warranted in pediatric patients at risk for perioperative endocarditis. DESIGN: Prospective nonrandomized clinical study. SETTING: Specialty care referral center. PATIENTS: Patients younger than 18 years undergoing diagnostic rigid tracheobronchoscopy for airway assessment. Twenty-five patients (14 boys and 11 girls) were enrolled. The mean age was 5.2 years (range, 10 months to 13 years). INTERVENTIONS: Blood samples for culture were obtained intraoperatively at 2 time intervals. The first culture was obtained after the induction of mask anesthesia prior to airway instrumentation; the second, within 5 minutes following the completion of tracheobronchoscopy. Blood cultures were performed under sterile technique and were placed into 20 mL of brain heart infusion broth. All cultures were incubated at 35 degrees C and observed for growth over a 14-day period. RESULTS: There were no documented cases of bacterial growth in blood cultures. All blood cultures, obtained before and after tracheobronchoscopy, were negative for bacterial growth after incubation for 14 days. Two culture bottles yielded contaminant organisms. CONCLUSIONS: Rigid tracheobronchoscopy in the pediatric population is a low-risk procedure for the development of bacteremia. This may bear on present guidelines regarding perioperative antibiotic prophylaxis for endocarditis in the high-risk population.

Adolescent↗
PubMed1999

Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness.

H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease.

Acidosis, Renal Tubular↗
PubMed1999

Immune response to pneumococcal conjugate and polysaccharide vaccines in otitis-prone and otitis-free children.

We compared responses to pneumococcal conjugate and polysaccharide vaccines in 48 otitis-free and 64 otitis-prone children. Pre- and postimmunization concentrations of antibodies to pneumococcal serotypes 6B, 14, 19F, and 23F were measured by enzyme-linked immunosorbent assay. Postimmunization mean concentrations of antibodies to all four serotypes were significantly higher for children receiving conjugate vaccine than for those receiving polysaccharide vaccine; the difference in responses was primarily due to a better response to conjugate vaccine in the otitis-prone group. Significantly higher postimmunization concentrations of antibodies to all four serotypes and to one of the four serotypes were found in otitis-prone children and otitis-free children who received conjugate vaccine, respectively. Pneumococcal conjugate vaccine has the potential to reduce the incidence of disease due to vaccine serotypes, even among children with recurrent otitis media.

Antibodies, Bacterial↗
PubMed1999

Leptin's actions on the reproductive axis: perspectives and mechanisms.

Energy availability influences reproductive fitness. The activity of the reproductive axis is sensitive to the adequacy of nutrition and the stores of metabolic reserves. The adipocyte-derived hormone leptin is postulated to reflect the state of nutrition and energy reserves and serve as a metabolic gate to the reproductive system. Genetically obese ob/ob mice (lacking endogenous leptin) are infertile, and treatment of these animals with exogenous leptin stimulates the activity of the reproductive endocrine system and induces fertility in both sexes. Severely food-restricted animals have reduced circulating levels of leptin, which are associated with markedly reduced secretion of the gonadotropins, LH, and FSH. Treatment of food-restricted mice, rats, sheep, and monkeys with exogenous leptin reverses the diet-induced inhibition of gonadotropin secretion. Leptin has also been suggested to have a role in timing the onset of puberty in several species, although evidence that leptin is the primary metabolic signal for initiating the onset of puberty in any species is controversial. Notwithstanding this debate, it is undisputed for all species studied to date that adequate levels of leptin in the circulation are essential (but not sufficient) for pubertal progression and that leptin treatment can reverse the delay in sexual maturation caused by food restriction. Double-label in situ hybridization studies in the brain of the mouse, rat, and monkey have revealed that hypothalamic neurons expressing proopiomelanocortin and neuropeptide Y coexpress the leptin receptor, whereas no evidence has been adduced that GnRH neurons express this receptor. Together, these observations suggest that leptin is a metabolic signal to the neuroendocrine reproductive system and that under conditions of inadequate energy reserves, low leptin levels act as a metabolic "gate" to inhibit the activity of the neuroendocrine reproductive axis in both sexes.

Aging↗
PubMed1999

A multidisciplinary approach to atypical lacrimal obstruction in childhood.

PURPOSE: This study explores the diagnosis and management of unusual anomalies involving the canaliculi, nasolacrimal duct, nasal cavity, and sinuses in childhood. METHODS: A case series of eight children with lacrimal outflow anomalies ranging from distal nasolacrimal duct cyst formation to persistent dacryocystitis following failed probing or silicone intubation were reviewed retrospectively. Diagnostic studies including intranasal endoscopy and preoperative or intraoperative dacryocystography (DCG) were of value. RESULTS: Treatment modalities included endoscopically guided resection of lacrimal cyst mucosa, endoscopic dacryocystorhinostomy (DCR), and monocanalicular or bicanalicular intubation of the lacrimal outflow system. In our series, endoscopic surgery was well tolerated by all patients with improvement in symptoms. CONCLUSIONS: This initial experience suggests that endoscopic techniques may be useful in the management of atypical lacrimal outflow obstruction in childhood.

Child↗
PubMed1999

The effect of a modified physical training program in reducing injury and medical discharge rates in Australian Army recruits.

This uncontrolled observational study examined the injury and medical discharge outcomes in 318 female and 1,634 male recruits as a result of changes to the Australian Army recruit physical training program. Changes included cessation of road runs, introduction of 400- to 800-m interval training, reduction in test run distance from 5 to 2.4 km, standardization of route marches, and the introduction of deep-water running. There was a 46.6% reduction in the rate of total injury presentation (chi 2 = 14.31, p = 0.0002) after the change. The annual rate of male medical discharges decreased 40.8% from 81.1/1,000 recruits in 1994/1995 to 47.0/1,000 recruits in 1995/1996 (chi 2 = 26.33, p = 0.0001). Female rates increased 58.3% from 104/1,000 recruits to 164.2/1,000 recruits (chi 2 = 6.09, p = 0.014). The decrease in the male medical discharge rate resulted in an estimated saving of $1,267,805 Australian. Bone scans were reduced by 50%, resulting in an estimated annual saving of $61,539 Australian. The disparity between male and female injury rates is a concern. The merits of mixed-gender physical training should be reviewed in the light of these observations, and the establishment of initial entry fitness standards for recruit training may need to be considered.

Adult↗
PubMed1998

Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis.

Primary distal renal tubular acidosis (dRTA) is characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Kindreds showing either autosomal dominant or recessive transmission are described. Mutations in the chloride-bicarbonate exchanger AE1 have recently been reported in four autosomal dominant dRTA kindreds, three of these altering codon Arg589. We have screened 26 kindreds with primary dRTA for mutations in AE1. Inheritance was autosomal recessive in seventeen kindreds, autosomal dominant in one, and uncertain due to unknown parental phenotype or sporadic disease in eight kindreds. No mutations in AE1 were detected in any of the autosomal recessive kindreds, and analysis of linkage showed no evidence of linkage of recessive dRTA to AE1. In contrast, heterozygous mutations in AE1 were identified in the one known dominant dRTA kindred, in one sporadic case, and one kindred with two affected brothers. In the dominant kindred, the mutation Arg-589/Ser cosegregated with dRTA in the extended pedigree. An Arg-589/His mutation in the sporadic case proved to be a de novo mutation. In the third kindred, affected brothers both have an intragenic 13-bp duplication resulting in deletion of the last 11 amino acids of AE1. These mutations were not detected in 80 alleles from unrelated normal individuals. These findings underscore the key role of Arg-589 and the C terminus in normal AE1 function, and indicate that while mutations in AE1 cause autosomal dominant dRTA, defects in this gene are not responsible for recessive disease.

Acidosis, Renal Tubular↗
PubMed1998

mu-Opioid agonist-stimulated [35S]GTPgammaS binding in guinea pig hypothalamus: effects of estrogen.

mu-Opioid receptors play a critical role in the regulation of the female reproductive cycle, and estrogen modulates the coupling of mu-opioid receptors to a potassium channel in the basal hypothalamus (BH) of the female guinea pig. Therefore, we ascertained the distribution of mu-opioid receptors in the BH with autoradiography using the mu-opioid selective agonist [3H]DAMGO. In addition, we investigated the effects of estrogen on DAMGO- or the GABAB receptor agonist baclofen-stimulated [35S]GTPgammaS binding in the BH. Based on the high density of mu-opioid receptors, but the lack of effects of estrogen on [35S]GTPgammaS binding, we conclude that mu-opioid receptor interaction with its G-protein is not the target of estrogen's actions.

Animals↗
PubMed1998

Slide tracheoplasty for long-segment tracheal stenosis.

OBJECTIVE: To introduce a novel surgical technique for the repair of congenital long-segment tracheal stenosis. DESIGN: Retrospective case series. SETTING: Tertiary-care hospital. PATIENTS: Three children ranging in age from 3 months to 3 years, all with complete tracheal rings, the stenotic segments representing between 36% and 49% of the total tracheal length. One patient had an anomalous right upper lobe bronchus and an associated pulmonary artery sling. INTERVENTION: Slide tracheoplasty reconstruction. MAIN OUTCOME MEASURE(S): Postoperative clinical status as evidenced by day and site of extubation, duration of hospitalization, number of bronchoscopic examinations performed before discharge, and subsequent need for urgent bronchoscopic examinations, which reflects the adequacy of the reconstructed airway. RESULTS: Two patients were extubated on the day of surgery, 1 intraoperatively; the child with the pulmonary artery sling required 3 days of elective intubation for postoperative ventilatory support. The duration of hospitalization ranged from 8 to 10 days. All patients underwent elective bronchoscopy once before discharge; none had granuloma formation. Follow-up ranged from 1 to 4 1/2 years. One patient required a single urgent bronchoscopic examination in addition to planned surveillance endoscopy. Growth of the reconstructed hemitracheal rings is demonstrable. CONCLUSIONS: Slide tracheoplasty achieves successful tracheal reconstruction using the patient's own tracheal tissues. Advantages of this method include the potential avoidance of cardiopulmonary bypass, immediate or early postoperative extubation, and the near-complete absence of granulation tissue formation. The latter obviates the need for multiple postoperative bronchoscopic examinations, as has been reported in tracheoplasty procedures using either costal cartilage or pericardium.

Child, Preschool↗
PubMed1998

Endonasal endoscopic dacryocystorhinostomy in children.

OBJECTIVE: To describe the indications, technique, and results of endonasal endoscopic dacryocystorhinostomy in children with congenital and acquired disorders of the nasolacrimal system. DESIGN: Retrospective case series. SETTING: Tertiary care hospital. PATIENTS: Four children ranging in age from 10 months to 6 years. INTERVENTION: Primary or revision endonasal endoscopic dacryocystorhinostomy performed via a joint otolaryngologic-ophthalmologic team approach. MAIN OUTCOME MEASURES: Incidence of surgical complications and postoperative clinical status. RESULTS: The duration of follow-up was 10 to 24 months with a successful clinical outcome in all 4 children. Two procedures were complicated by nasal vestibule skin abrasions secondary to rotation of the drill shaft. CONCLUSIONS: Despite the technical challenges posed by the small anatomical dimensions of the pediatric nasal airway, the combination of proper otolaryngologic endoscopic instrumentation and ophthalmologic lacrimal sac transillumination guidance allows for the safe and successful performance of endonasal endoscopic dacryocystorhinostomy in the pediatric population.

Child↗
PubMed1998

The treatment of gastric mucosal prolapse syndrome with laparoscopic nissen fundoplication.

Gastric mucosal prolapse occurs when a portion of the mucosa of the stomach herniates into the esophagus, resulting in massive hemorrhage. A 19-year-old man presented on two occasions with an upper gastrointestinal hemorrhage as a result of this syndrome. He was definitively treated with a laparoscopic Nissen fundoplication. This case report outlines his presentation, defines and details gastric mucosal prolapse, and discusses the treatment of this syndrome with laparoscopic Nissen fundoplication.

Adult↗
PubMed1998

Direct measurements of temperature and humidity in dust mite microhabitats.

BACKGROUND: Up to 70% of atopic asthmatics have a positive skin test to the dust mite allergen Der p 1. Reduction of dust mite numbers by lowering room humidity control is one suggested technique for reducing dust mite allergen levels to clinically acceptable levels. Trials of this technique in temperate climates have reported mixed results. It has been speculated that one reason for this is that humidity changes in room ambient air are not tightly linked to humidity changes in the dust mite microenvironment (in the base of carpets, bedding, furniture etc.). OBJECTIVE: To directly measure humidities and temperatures in dust mite microenvironments and compare these to ambient conditions, and so gather data on how the microclimates are influenced by room conditions and moisture and heat sources, such as an occupant in a bed. METHODS: A special small humidity device has been developed which can discriminate humidity changes over distances of millimetres. With these devices microclimates have been measured in the base of carpets, in layers through bedding, and in furniture. RESULTS: Measured base-of-carpet humidities were significantly higher than room humidities. Bedding relative humidities show complex behaviour according to the distance separation between the measuring point and the occupant. Immediately below the occupant, bed relative humidities fall when the person enters the bed. Similar behaviour is observed in a sofa. CONCLUSION: Some dust mite microclimates have been shown to be very different from room conditions. Consequently, reduction of dust mite numbers and allergen levels cannot be guaranteed by the controlling of room humidities.

Allergens↗