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Biomedical subjects

S J Cunningham

Publications and source records attributed to S J Cunningham.

At least 55 records · Page 3Linked to original sources
PubMed1996

Preparation, perceptions, and problems: a long-term follow-up study of orthognathic surgery.

Follow-up of patients who have undergone orthognathic surgery is well documented in the literature, usually in the form of questionnaire-based studies or clinical interviews. However, there have been few long-term follow-up investigations. This study aimed to look at the long-term outcomes of such operative procedures. Questionnaires were sent to 68 patients who had undergone joint orthodontic and orthognathic surgery procedures 5 to 16 years previously, after the patients were contacted by telephone to learn the nature of the study. The 49 responses were compared with a previously analyzed preoperative group and a short-term postoperative group (1 to 3 years following surgery) from the same institution. Respondents showed high levels of satisfaction overall, with the majority believing they had made the correct decision to undergo surgery. The main problem areas identified were those concerning presurgical explanations and lack of advice regarding side-effects. This area requires improvement as postsurgical dissatisfaction can be minimized by accurate descriptions of the treatment. A number of respondents reported persistent lip paresthesia and continued limitation of mouth opening. However, the majority of patients commented that these persistent symptoms had no effect on their daily life.

Adult↗
PubMed1995

Investigation of the active site cysteine residue of rat liver mitochondrial aldehyde dehydrogenase by site-directed mutagenesis.

To determine the active site cysteine residue in aldehyde dehydrogenase, we mutated amino acid residues 49, 162, and 302 of recombinantly expressed rat liver mitochondrial (class 2) aldehyde dehydrogenase. The C49A and C162A mutants were fully active tetrameric enzymes, although the C162A mutant was found to be highly unstable. The C302A mutant was also a tetramer and bound coenzyme, but lacked both dehydrogenase and esterase activities. To test for the role of cysteine 302 as a nucleophile, the residue was mutated to a serine, a poor nucleophile. this C302S mutant was active but was a much poorer catalyst, with a kcat/Km value 7 x 10(5) times lower than that of the recombinant native enzyme. Unlike with native enzyme where deacylation is rate limiting, formation of the serine hemiacetal intermediate appeared to be the rate-limiting step. Cysteine 302 is the only strictly conserved cysteine residue among all the available sequences of the aldehyde dehydrogenase superfamily, supporting the role of this residue as the active site nucleophile of aldehyde dehydrogenase.

Aldehyde Dehydrogenase↗
PubMed1995

Metered-dose inhalers with spacers vs nebulizers for pediatric asthma.

OBJECTIVE: To determine whether the administration of beta-agonists by metered-dose inhaler (MDI) with a spacer device is as effective as the administration of beta-agonists by nebulizer for the treatment of acute asthma exacerbations in children. DESIGN: Randomized trial with two arms. SETTING: Urban pediatric emergency department (ED) in Bronx, NY. PATIENTS: Convenience sample of 152 children 2 years and older with a history of at least two episodes of wheezing presenting to the ED with an acute asthma exacerbation. INTERVENTIONS: Patients were randomly assigned to receive standard doses of a beta-agonist (albuterol) by an MDI with spacer or by a nebulizer. Dosing intervals and the use of other medications were determined by the treating physician. MEASUREMENTS/MAIN RESULTS: Baseline characteristics and asthma history were recorded. Asthma severity score, peak expiratory flow rate in children 5 years or older, and oxygen saturation were determined at presentation and before admission or discharge. The groups did not differ in age, sex, ethnicity, age of onset of asthma, or asthma severity score at presentation. There were no significant differences between the groups in outcomes, including mean changes in respiratory rate, asthma severity score, and peak expiratory flow rate, oxygen saturation, number of treatments given, administration of steroids in the ED, and admission rate. Patients given MDIs with spacers required shorter treatment times in the ED (66 minutes vs 103 minutes, P < .001). Fewer patients in the spacer group had episodes of vomiting in the ED (9% vs 20%, P < .04), and patients in the nebulizer group had a significantly greater mean percent increase in heart rate from baseline to final disposition (15% vs 5%, P < .001). CONCLUSIONS: These data suggest that MDIs with spacers may be an effective alternative to nebulizers for the treatment of children with acute asthma exacerbations in the ED.

Acute Disease↗
PubMed1995

Delusional depression, hyperparathyroidism, and ECT.

A woman with delusional depression and unsuspected primary hyperparathyroid disorders responded completely to electroconvulsive therapy (ECT). Hypercalcemia is a complicating factor in the treatment of delusional depression, but there is little evidence that it is causative and the use of ECT should not be delayed. The case adds to the literature confirming the efficacy and safety of ECT with physically ill patients when it may be a life-saving procedure.

Aged↗
PubMed1995

Psychological aspects of orthognathic surgery: a review of the literature.

A review of the literature clearly shows that dental and facial disfigurements have significant effects and can be an important social disadvantage. The motivational patterns of patients requesting orthognathic surgery are many and varied, but a desire for improvement in esthetics and alleviation of functional problems are the two most commonly cited reasons. The careful assessment of patients requesting orthognathic surgery is imperative, because the success of surgery may well depend on careful patient selection. Care must be taken with those patients suspected of exhibiting dysmorphophobic tendencies and, if there is any doubt, psychiatric referral should be undertaken. Patient satisfaction following orthognathic surgery has been reported as high overall, as has been the number of patients who have said they would re-elect to have surgery. Many of the studies found that patients had improved self-confidence and social skills after treatment.

Esthetics↗
PubMed1994

Effects of changing glutamate 487 to lysine in rat and human liver mitochondrial aldehyde dehydrogenase. A model to study human (Oriental type) class 2 aldehyde dehydrogenase.

Many Oriental people possess a liver mitochondrial aldehyde dehydrogenase where glutamate at position 487 has been replaced by a lysine, and they have very low levels of mitochondrial aldehyde dehydrogenase activity. To investigate the cause of the lack of activity of this aldehyde dehydrogenase, we mutated residue 487 of rat and human liver mitochondrial aldehyde dehydrogenase to a lysine and expressed the mutant and native enzyme forms in Escherichia coli. Both rat and human recombinant aldehyde dehydrogenases showed the same molecular and kinetic properties as the enzyme isolated from liver mitochondria. The E487K mutants were found to be active but possessed altered kinetic properties when compared to the glutamate enzyme. The Km for NAD+ at pH 7.4 increased more than 150-fold, whereas kcat decreased 2-10-fold with respect to the recombinant native enzymes. Detailed steady-state kinetic analysis showed that the binding of NAD+ to the mutant enzyme was impaired, and it could be calculated that this resulted in a decreased nucleophilicity of the active site cysteine residue. The rate-limiting step for the rat E487K mutant was also different from that of the recombinant rat liver aldehyde dehydrogenase in that no pre-steady-state burst of NADH formation was found with the mutant enzyme. Both the rat native enzyme and the E487K mutant oxidized chloroacetaldehyde twice as fast as acetaldehyde, indicating that the rate-limiting step was not hydride transfer or coenzyme dissociation but depended upon nucleophilic attack. Each enzyme form showed a 2-fold activation upon the addition of Mg2+ ions. Substituting a glutamine for the glutamate did not grossly affect the properties of the enzyme. Glutamate 487 may interact directly with the positive nicotinamide ring of NAD+ for the Ki of NADH was the same in the lysine enzyme as it was in the glutamate form. Because of the altered NAD+ binding properties and kcat of the E487K variant, it is assumed that people possessing this form will not have a functional mitochondrial aldehyde dehydrogenase.

Aldehyde Dehydrogenase↗
PubMed1994

A region on the human thyrotropin receptor which can induce antibodies that inhibit thyrotropin-mediated activation of in vitro thyroid cell function also contains a highly immunogenic epitope.

Autoantibodies to the thyrotropin receptor (TSHr) bind to the extracellular domain of the TSHr (ETSHr) and either stimulate or inhibit thyroid cell function and/or growth. In order to investigate the regulation and the specificity of the immune response to the TSHr, our laboratory recently produced recombinant human ETSHr protein by using the baculovirus expression system. In the present study, we used the recombinant ETSHr protein, a panel of overlapping synthetic peptides derived from the TSHr, and polyclonal rabbit antibodies produced against recombinant ETSHr and synthetic peptides to define a highly immunogenic region (aa 352-388) of the TSHr. Moreover, we used competitive inhibition studies to identify a dominant epitope (aa 367-372) within this region to which ETSHr antibodies react. This immunodominant epitope lies within a region unique to the TSHr when compared to the other glycoprotein hormone receptors. These data, together with the earlier observation that antibodies against aa region 357-372 can inhibit thyrotropin (TSH)-mediated activation of thyroid cells in culture, show that aa 367-372 represents, an immunodominant epitope within a functionally important region which is unique to the TSHr. Therefore, this region may play an important role in the induction or modulation of the specific immune response against the TSHr.

Amino Acid Sequence↗
PubMed1994

Seroprevalence of hepatitis B and C in a Merseyside hospital for the mentally handicapped.

This study reports the prevalence of antibodies to hepatitis B virus (HBV) and C virus (HCV), and the frequency of potential exposure to these viruses among patients and staff in six long-stay wards of a hospital caring for mentally handicapped adults from the Mersey region. A retrospective survey of risk behaviour among 134 patients and questionnaire survey of 75 nursing staff was performed. Serum samples from both groups were tested for HBV markers and patient sera for antibodies to HCV by enzyme-linked immunosorbent assay (ELISA). None of the 102 patients tested had antibodies against HCV, although 17 had detectable antibody to HBV core (anti-HBc). Seven out of the 17 were positive for HBV surface antigen. None was positive for IgM antibody to HBV core. Only 1 out of 61 staff had anti-HBc and none was positive for surface antigen. Twenty-nine of 75 (39%) staff reported bites sufficient to break the skin and 52 (69%) significant other injuries from patients; 25 (31%) of staff had not received HBV vaccination. None of the patients had received HBV vaccine. We conclude that HCV does not appear to be a major hazard in this closed community but the prevalence of HBV markers indicating past exposure among patients is high, vaccine uptake is incomplete and incidents which may allow viral transmission are frequent.

Adult↗
PubMed1994

Thyrotropin (TSH) interacts with multiple discrete regions of the TSH receptor: polyclonal rabbit antibodies to one or more of these regions can inhibit TSH binding and function.

As a means of identifying functional regions of the TSH receptor (TSHr), we immunized four rabbits with recombinant extracellular TSHr (ETSHr) protein and systematically evaluated their antibody response. The antibody response was characterized by testing serial serum samples for immunoglobulin G (IgG) against ETSHr protein and 26 synthetic peptides which span the entire ETSHr. Sera were also tested for their ability to block TSH binding to native TSHr. All four rabbits developed high serum IgG titers (>1:100,000) to ETSHr. None of the rabbits developed significant IgG titers against 11 of the peptides, but each showed persistent high titers against several of the others. After multiple inoculations of antigen, sera from 3 rabbits showed significant ability to block TSH binding. Based on the ability of peptides to reverse this blocking activity, we identified 3 regions of the TSHr (i.e. amino acids 292-311, 367-386, and 397-415) through which antibodies can block TSH binding. Moreover, antibodies purified on either peptide 292-311 or peptide 367-386 affinity columns could block both TSH binding and TSH-mediated activation of thyroid cells in culture. These studies show ETSHr protein is sufficient to induce production of functionally relevant antibodies. Furthermore, we have identified several sites on the TSHr through which antibodies can inhibit TSH binding, thus leading to identification of several potential TSH-binding regions.

Amino Acid Sequence↗
PubMed1994

Reduction of morbidity in asthmatic children given a spacer device.

STUDY OBJECTIVE: To evaluate whether providing a spacer device and a single, brief demonstration regarding its proper use would result in earlier resolution of asthma symptoms, improved school attendance, and decreased frequency of unscheduled medical visits for asthma among children receiving noncontinuous care in an urban emergency department (ED). DESIGN: Randomized controlled trial. SETTING: Urban hospital pediatric ED. PARTICIPANTS: Eighty-four children with the chief complaint of asthma. INTERVENTION: Children were enrolled in the ED at the time of an asthma attack and randomly assigned to one of two treatment groups. The spacer group received an inhaled beta-agonist at discharge from the ED with a spacer device. The control group received inhaled or oral beta-agonists without a spacer device. Both groups received other medications at the discretion of the evaluating physician who was not the interviewer in any case. A baseline questionnaire was completed and follow-up by telephone was done at 1 week, and 2, 4, and 6 months after enrollment. MEASUREMENTS AND RESULTS: The spacer group reported significantly earlier resolution of wheezing (0 days vs 2 days, p < 0.01) at the 2- and 4-month follow-up assessments. They reported significantly fewer days of cough after an asthma attack at 2 months (1 day vs 3 days, p < 0.01) and 4 months (0 days vs 3 days, p < 0.01). The spacer group missed significantly fewer days of school following an asthma attack at 2 and 4 months (0 days vs 2 days, p = 0.05). There was no difference between the two groups on any outcome measures at the 1-week and 6-month follow-up assessments. CONCLUSIONS: Introducing a spacer device to patients in a busy, inner-city pediatric ED is an effective and efficient intervention that improves the functioning of asthmatic children in terms of resolution of cough and wheeze and school absenteeism.

Absenteeism↗
PubMed1991

Molecular cloning of the mitochondrial aldehyde dehydrogenase gene of Saccharomyces cerevisiae by genetic complementation.

Mutants of Saccharomyces cerevisiae deficient in mitochondrial aldehyde dehydrogenase (ALDH) activity were isolated by chemical mutagenesis with ethyl methanesulfonate. The mutants were selected by their inability to grow on ethanol as the sole carbon source. The ALDH mutants were distinguished from alcohol dehydrogenase mutants by an aldehyde indicator plate test and by immunoscreening. The ALDH gene was isolated from a yeast genomic DNA library on a 5.7-kb insert of a recombinant DNA plasmid by functional complementation of the aldh mutation in S. cerevisiae. An open reading frame which specifies 533 codons was found within the 2.0-kb BamHI-BstEII fragment in the 5.7-kb genomic insert which can encode a protein with a molecular weight of 58,630. The N-terminal portion of the protein contains many positively charged residues which may serve as a signal sequence that targets the protein to the mitochondria. The amino acid sequence of the proposed mature yeast enzyme shows 30% identity to each of the known ALDH sequences from eukaryotes or prokaryotes. The amino acid residues corresponding to mammalian cysteine 302 and glutamates 268 and 487, implicated to be involved at the active site, were conserved. S. cerevisiae ALDH was found to be localized in the mitochondria as a tetrameric enzyme. Thus, that organelle is responsible for acetaldehyde oxidation, as was found in mammalian liver.

Aldehyde Dehydrogenase↗
PubMed1989

"Challenges in pain management". Part 4. Teaching coping strategies to adolescents with migraine.

A treatment program was developed involving cognitive and behavioral strategies for the treatment of migraine headaches with adolescents at the Children's Hospital of Eastern Ontario. These techniques include: a headache diary, progressive relaxation techniques, cognitive restructuring, distraction or attention focusing, mental activities, thought stopping, imagery, behavior rehearsal, assertiveness and problem solving. The article details the therapeutic use of these techniques. An analysis of each strategy is presented in three sections: a rationale to the adolescent, recommendations to the therapist and a troubleshooting section.

Adaptation, Psychological↗