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Biomedical subjects

T C Brown

Publications and source records attributed to T C Brown.

At least 19 recordsLinked to original sources

Expression level dependent changes in the properties of P2X2 receptors.

The currents of P2X(2) receptors expressed in Xenopus oocytes or HEK293 cells show significant cell-to-cell variation in many properties including the rate of desensitization and the magnitude of potentiation by zinc or acidic pH. In this study, we examined whether differences in expression levels underlie this variability. We injected Xenopus oocytes with different concentrations of RNA encoding rat P2X(2) to give a wide range of maximum current amplitudes, and then measured the potentiation of responses to 10 micro M adenosine 5'-triphosphate (ATP) by zinc or acidic pH. Individual oocytes showed potentiation ratios that ranged from 1.4- to 25-fold. Oocytes with small amplitude responses to a saturating concentration of ATP tended to have larger potentiation ratios than oocytes with large amplitude responses. This phenomenon was explained by an inverse correlation between the EC(50) for ATP and the maximum current amplitude, with the EC(50) decreasing from about 37 to 7 micro M as expression level increased. In contrast, the Hill coefficient was not correlated with the maximum current amplitude. Truncated receptors lacking the last 76 amino acids also showed an inverse correlation between the EC(50) and the maximum current amplitude. Thus, the interactions that cause expression-dependent changes in P2X(2) receptor properties must involve domains proximal to position H397.

Adenosine Triphosphate↗

Anaesthesia and pain management in cerebral palsy.

Cerebral palsy is the result of an injury to the developing brain during the antenatal, perinatal or postnatal period. Clinical manifestations relate to the area affected. Some of the conditions associated with cerebral palsy require surgical intervention. Problems during the peri-operative period may include hypothermia, nausea and vomiting and muscle spasm. Peri-operative seizure control, respiratory function and gastro-oesophageal reflux also require consideration. Intellectual disability is common and, in those affected, may range from mild to severe. These children should be handled with sensitivity as communication disorders and sensory deficits may mask mild or normal intellect. They should be accompanied by their carers at induction and in the recovery room as they usually know how best to communicate with them. Postoperative pain management and the prevention of muscle spasm is important and some of the drugs used in the management of spasm such as baclofen and botulinum toxin are discussed. Epidural analgesia is particularly valuable when major orthopaedic procedures are performed.

Analgesia↗

Effects of the laryngeal mask airway on the lower oesophageal barrier pressure in children.

The effects of laryngeal mask airway (LMA) insertion and cuff inflation on lower oesophageal sphincter, gastric and barrier pressure, and the relationship of the LMA cuff pressure and volume on the change in the barrier pressure were studied in 20 children. Subjects were aged one to five years, undergoing eye examination under general anaesthesia. There was no significant change in barrier pressure after insertion and inflation of the LMA compared with baseline measures. The cuff pressure and volume were not related to the change in barrier pressure. Two patients had marked decreases (10 to 15 mmHg) in barrier pressure after the LMA insertion. These decreases in barrier pressure would be expected to increase the risk of gastro-oesophageal reflux. We conclude that, although LMA use had little effect on barrier pressure in most children, occasional children will have potentially clinically significant decreases in barrier pressure with use of the LMA.

Anesthesia, General↗

The etiology of intestinal obstruction in patients without prior laparotomy or hernia.

Patients with clinical features of intestinal obstruction without a history of prior laparotomy or physical evidence of a hernia can be a diagnostic challenge. We attempted to evaluate our preoperative diagnostic accuracy, to assess the effectiveness of our diagnostic tools, and to determine the incidence of various causes of intestinal obstruction in this select group. Medical records of all patients admitted to our institution and taken to surgery with a diagnosis of intestinal obstruction from 1975 through 1995 were reviewed. Patients with a history of prior laparotomy, evidence of hernia, or emergent indications for surgery on admission were excluded. The most common cause of intestinal obstruction in this select group of patients was malignancy. The ability to detect malignancy preoperatively is significantly better than the ability to detect benign causes of obstruction (Pearson Chi square = 4.09 with a P value of 0.04). Preoperative detection of malignancy in these patients is critical for optimal treatment planning and counseling for patients and their families.

Adolescent↗

Instability of the FMR2 trinucleotide repeat region associated with expanded FMR1 alleles.

The fragile sites FRAXA and FRAXE, located approximately 600 kb apart on Xq27.3 and Xq28, respectively, are due to a CGG trinucleotide repeat expansion. Although the expansion mechanism for these and other trinucleotide repeat disorders remains unknown, the similarities between the FRAXA and FRAXE regions suggest a possible association between the 2 sites. DNA from 953 individuals was analyzed to determine the distribution of FRAXE repeat sizes in this population and to ascertain potential association between FRAXA and FRAXE repeat sizes. Thirty-four FMR2 alleles ranging from 3-42 repeats were identified. No FRAXE expansions were found in this population, supporting previous findings that FRAXE expansions are rare. However, in the fragile X syndrome affected group, a FMR2 delection, 2 cases of FRAXE repeat instability and a FRAXE mosaic male were identified. Also, a previously identified, rare FMR2 polymorphism was observed. Statistical analysis showed no correlation between normal FRAXA and FRAXE repeat sizes studied, although there was a significant size difference in larger FMR2 alleles that segregated with expanded FMR1 alleles. These findings support the idea of an association between repeat expansion in the FMR1 gene and instability or deletions in the FMR2 gene.

Base Sequence↗

Paediatric tracheobronchomalacia and its assessment by tracheobronchography.

Tracheobronchomalacia (TBM) is a rare condition that results in abnormal compliance of the airways with airway collapse being most marked in expiration. In a series of 28 patients, it was observed that a majority of cases presented with malacia involving the trachea (64%) and the left main bronchus (64%) alone. The right main bronchus was involved in combination with the trachea in 32%, but rarely was involved by itself. Most patients demonstrated associated congenital abnormalities, such as tracheo-oesophageal fistulae, vascular rings or congenital heart disease (78%). A small proportion were premature infants with no obvious associated abnormality (11%). Evaluation of the dynamic process, tracheobronchomalacia; requires 'real-time' investigation. While computed tomography (CT) and magnetic resonance imaging (MRI) have their role in the management of chronic airway obstruction in the child, only cine-CT, bronchoscopy, fluoroscopy and tracheobronchography provide real-time assessment for the evaluation of a dynamic process such as TBM. In our experience, tracheobronchography provides excellent anatomic, physiologic and therapeutic information in the assessment of those infants with primary or secondary TBM. By using continuous positive airway pressure in incremental doses, the amount of positive pressure required to maintain an open airway in expiration is a valuable adjunct to the clinical management of the patient. When careful attention is paid to technique, tracheobronchography is a safe investigation in experienced hands.

Bronchial Diseases↗

Anaesthesia for children with mucopolysaccharidoses.

The mucopolysaccharidoses are a group of inherited disorders of metabolism, with varying clinical manifestations. A number of them present anaesthetic difficulties. This paper presents a summary table of the syndromes and reviews our experience over ten years with patients with these diagnoses. The clinical presentations, anaesthetic management, and complications are described. The effect of age and diagnosis on airway difficulties was studied. There were 31 patients, 28 of whom required anaesthesia, on a total of 99 occasions, for 115 procedures. The patients with Hunter, Hurler and Maroteaux-Lamy syndromes had significantly more airway difficulties as they grew older, and compared with patients in this group with other syndromes. Patients with Hurler's syndrome may have coronary artery involvement and one patient was given fentanyl and pancuronium for this reason. He proved impossible to intubate and an emergency tracheostomy was performed.

Adolescent↗

Evaluation of cutaneous photodamage using a photographic scale.

Clinical assessments of photodamage are based upon a subjective evaluation of characteristic features such as wrinkling and pigmentary change, and are influenced by inter-observer differences in grading criteria. In an effort to standardize the grading of photodamage severity, we have developed a six-point photographic scale in which each of the six grades of overall photodamage severity is depicted by three photographs. The use of three photographs to portray each grade illustrates the diversity and range of manifestations within each grade. This photographic scale was tested by two groups of dermatologists, who used it on two occasions to grade the overall photodamage severity of a single group of female Caucasian subjects. Results indicate high inter-observer agreement, with chance-corrected agreement ranging from 0.44 to 0.63 and from 0.54 to 0.76 on the first and second occasions, respectively. Intra-observer repeatability was high, with chance-corrected agreement ranging from 0.56 to 0.78. Inter- and intra-observer differences were within one category in nearly all cases. Similar grades were assigned by dermatologists with and without experience in treating photodamaged patients. We conclude that application of this scale results in consistent and reproducible clinical evaluations of overall photodamage severity in Caucasian subjects. The scale may be useful in categorizing subjects for epidemiological studies, or in selecting patients for clinical trials.

Dermatology↗

Reduction of bowel motion artifact during digital subtraction angiography: a comparison of hyoscine butylbromide and glucagon.

The authors compared the effectiveness of hyoscine butylbromide (Buscopan) and glucagon in reducing bowel motion artifact during abdominal intra-arterial digital subtraction angiography. Sixty-six patients referred to the radiology department of a tertiary-care hospital for abdominal angiography between October 1989 and July 1992 consented to participate in the study. Diabetic patients receiving insulin and those with glaucoma were not considered for the study. The patients were assigned at random to receive either Buscopan (39 patients) or glucagon (27) intravenously before angiography. Images obtained at three stages during the procedure were reviewed independently by three experienced vascular radiologists who were blinded as to treatment group; images for nine patients in the Buscopan group and seven in the glucagon group were excluded because of breathing artifact or body movement. For each image the radiologists scored bowel motion in each section of a six-section grid. The bowel motion scores during early, middle and late arterial phases and the total scores for the two groups did not differ significantly (t-test). On the basis of these findings, the authors continue to use Buscopan because it is less expensive than glucagon.

Angiography, Digital Subtraction↗

Financial analysis of a family practice residency threatened with closure.

Family practice residency programs often find themselves needing to fiscally justify their existence to their sponsoring institutions. One such program in a community hospital was threatened with closure, to be replaced by salaried and/or fee-for-service physicians. We present an applied research methodology for comparing the residency budget and revenues with that of a replacement delivery system with no educational mission. The total expenses for nonresidency physicians were projected to be from 10.5% to 25.1% less than the residency budget. Revenues generated by nonresidency physicians were projected to be from 29.4% to 37.6% less than those of the residency, primarily due to the loss of grants and graduate medical education reimbursement through the Medicare program. Proposed reductions in grants and graduate medical education reimbursement threaten the budget/revenue balance of this and other family practice residency programs.

Budgets↗