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Biomedical subjects

M J Cunningham

Publications and source records attributed to M J Cunningham.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The odontogenic keratocyst: a 20-year clinicopathologic review.

The odontogenic keratocyst (OKC) is a jaw cyst with a proclivity for local invasion and recurrence. This 20-year retrospective study was conducted to evaluate methods of treatment and recurrence rates. Forty-nine patients were identified with an average age at presentation of 39.5 years. The molar region of either the mandible or maxilla was the principal primary location; the maxillary antrum was also a common site. The majority of cysts were unilocular and associated with adjacent dentition. Initial therapy was typically enucleation with or without extraction of associated teeth; seven cases of recurrent or second primary odontogenic keratocysts required more extensive surgery. Follow-up ranged from 1 to 15 years with an average duration of 4.3 years. The overall recurrence rate was 35%, and the average time to recurrence 4 years. A recurrence rate of 60% was documented for patients with basal cell nevus syndrome or a family history thereof. Long-term follow-up is necessary following initial OKC treatment. The high rate of recurrence in patients with documented or suspected basal cell nevus syndrome suggests the need for more aggressive initial surgical management in this selected patient population.

Adult↗

The stimulatory effect of leptin on the neuroendocrine reproductive axis of the monkey.

Leptin acts as a metabolic activator of the neuroendocrine reproductive axis in several rodent species, but whether leptin plays a similar role in primates is unknown. To explore this question, we examined the effects of leptin on gonadotropin and testosterone secretion in male rhesus monkeys that were fasted for 2 days. Mean plasma levels of LH and FSH, LH pulse frequency, and LH pulse amplitude were significantly higher in leptin-treated animals compared with saline-treated controls during the second day of the fast. To identify targets for leptin's action, we used in situ hybridization and computerized imaging to map leptin receptor (Ob-R) messenger RNA (mRNA) distribution. Ob-R mRNA was observed in the anterior pituitary and several areas of the brain, including the arcuate and ventromedial nuclei of the hypothalamus. Ob-R mRNA was coexpressed in both POMC and neuropeptide Y neurons in the arcuate nucleus, whereas little or no coexpression of Ob-R mRNA was evident in GnRH neurons. These results suggest that leptin is a metabolic signal to the reproductive axis in primates and imply that both POMC and neuropeptide Y neurons are involved in mediating leptin's effects in the brain.

Animals↗

Treatment of aural foreign bodies in children.

OBJECTIVE: To determine the proper treatment of children and adolescents with foreign bodies of the external auditory canal (EAC). DESIGN: Retrospective case series. SETTING: Specialty care referral hospital. PATIENTS: All patients younger than 18 years of age who presented in the emergency ward or office setting with a foreign body of the EAC during a 5-year period. RESULTS: One hundred ninety-one patients with aural foreign bodies were identified. Age at presentation ranged from 10 months to 17 years with 141 patients (74%) younger than 8 years old. Twenty-seven different objects were encountered with pebbles, beads, insects, and plastic toys the most common. Fifty-seven (30%) of the patients required surgical removal of the aural foreign body under general anesthesia. CONCLUSION: Adequate immobilization and proper instrumentation allow the uncomplicated removal of many EAC foreign bodies in the pediatric population. The use of general anesthesia is preferred in very young children and in children of any age with aural foreign bodies whose contour, composition, or location predispose to traumatic removal in the ambulatory setting. Criteria for otolaryngologic referral and consideration of operative microscopic removal are outlined.

Adolescent↗

Osseous craniofacial arteriovenous malformations in the pediatric population.

Osseous craniofacial arteriovenous malformations are rare and challenging entities. A 20-year retrospective review at our institutions identified 47 cases of craniofacial arteriovenous malformations, 3 of which were in children with extensive osseous facial structure involvement. Diagnostic evaluation included computed tomography, magnetic resonance imaging, and angiography. A 3-stage treatment protocol employed both transarterial embolization and direct intralesional puncture embolization followed by complete surgical resection. Mean intraperative blood loss was limited to 1000 mL. There were no complications during therapy. All 3 patients are without recurrence at 2- to 4-year follow-up. Osseous craniofacial arteriovenous malformations should be approached with multimodality therapy, incorporating interventional neuroradiologic and surgical management. Using the outlined protocol, these lesions can be treated safely and effectively.

Adolescent↗

Tubeless spontaneous respiration technique for pediatric microlaryngeal surgery.

BACKGROUND: Tubeless spontaneous respiration technique for pediatric microlaryngeal surgery may be accomplished using different anesthetic protocols. Two methods, inhalation of volatile anesthetic agents alone and in combination with intravenous propofol, are reviewed with regard to intraoperative airway stability, post-operative morbidity, recovery room course, and halothane concentration required during maintenance anesthesia. DESIGN: Retrospective case series. SETTING: Otolaryngology referral hospital. PATIENTS AND METHODS: Twenty-nine microlaryngeal procedures were performed using tubeless spontaneous respiration technique in children ranging from 2 weeks to 11 years of age. The following 2 anesthetic protocols were used: inhaled volatile anesthetic agents alone in 18 procedures and in combination with intravenous propofol in 11. Anesthesia, surgery, and recovery room times were documented. Specific characteristics of anesthetic maintenance, including total anesthetic gas flow (liters per minute), variations of halothane concentration (percentage), and duration of halothane administration (minutes) were also recorded to calculate the mean concentration of halothane (percentage) delivered to each patient. RESULTS: No statistical differences were observed between the 2 protocols in terms of anesthesia and surgical outcomes. Adjusting for differences in patient age, weight, maintenance duration, and total anesthetic gas flow, the introduction of propofol allowed a statistically significant reduction in the mean concentration of halothane required during maintenance anesthesia. CONCLUSIONS: Both tubeless spontaneous respiration technique protocols proved successful in this study. However, the addition of propofol allowed a significant reduction in the halothane requirement during anesthesia maintenance. This has the potential benefit of decreasing the exposure of operating room personnel to volatile anesthetics during tubeless spontaneous respiration technique.

Anesthesia, General↗