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Biomedical subjects

B Fraser

Publications and source records attributed to B Fraser.

At least 19 recordsLinked to original sources
PubMed2001

Are antipsychotic drugs the right treatment for challenging behaviour in learning disability?: The place of a randomised trial.

People with learning disability sometimes display challenging behaviour. This can be managed by use of antipsychotic medication or behavioural therapy or both. There is no solid evidence, however, that these therapies are safe and effective. A randomised controlled trial of antipsychotic medication has been proposed to deliver such evidence. However, this presents difficult issues in the ethics of research with learning disabled people. In particular, is a trial the most efficient and fairest way to evaluate practice in this area? This paper reviews the clinical situation, gives the rationale for the trial, and analyses the ethical arguments for and against such a trial.

Antipsychotic Agents↗
PubMed2000

Randomised trial of iodine intake and thyroid status in preterm infants.

BACKGROUND: Low levels of circulating thyroid hormones have been associated with poorer general and neurodevelopmental outcome in preterm babies and it has been speculated that the association is causal. Low levels of circulating thyroid hormone have been reported after inadequate intake of iodine in preterm infants being fed milk formula. AIM: To investigate whether increased iodine intake from supplemented preterm formula would improve thyroid hormone levels in preterm babies (this study) and hence improve neurodevelopmental status (planned subsequent study). METHOD: A total of 121 preterm infants were entered into a randomised controlled trial of standard (68 microg/l) versus increased (272 microg/l) iodine in preterm formula. RESULTS: The two groups were comparable at recruitment. No evidence of an effect of the intervention on thyroid hormone levels was seen up to 41 weeks after conception. CONCLUSION: Calls for increased iodine content of preterm infant formulas are not justified by this study.

Female↗
PubMed1999

Stressors and concerns in teen asthma.

Adolescents are uniquely susceptible to poor outcome with asthma because of their desire for autonomy, denial of disease, preference for immediate gain rather than prophylaxis, restricted ability to control their psychosocial and physical environment, and difficult transition to health care. Tobacco smoking as well as related drug abuse and passive exposure to tobacco is a major obstacle to managing adolescent asthma, together with atopy and psychosocial problems. Recent investigations indicate that adolescents are uniquely susceptible to tobacco industry promotions and logos because of these developmental characteristics. By understanding adolescent development, behavior and peer group impact, with its spectrum from early to late adolescence, clinicians can target their educational interventions more successfully in asthma. Health care provision for the adolescent with asthma requires a multidisciplinary team spearheaded by a primary care provider with the expert guidance of an allergist, outreach nurse, mental health worker, and social service representative. This care must be negotiated with an appropriate educational plan on the basis of NHLBI guidelines to be successful. Medications should be prescribed no more than twice a day, whenever possible, in conjunction with an action plan on the basis of peak flow readings to warn the adolescent when to use more medication and when to call the clinician. The plan should empower adolescents by recognizing their need for autonomy with self-management, enabling them to have a safe and comfortable lifestyle, and being physically and mentally at ease with their peers, family, school, and work environments.

Adolescent↗
PubMed1998

Physiological effects of thermal stress on aviators flying a UH-60 helicopter simulator.

An evaluation of the physiological effects on aviators of heat stress (90 degrees F wet bulb globe temperature [WBGT]) versus a cooler condition (70 degrees F WBGT) when wearing either a MOPP0 (Mission-Oriented Protective Posture 0) uniform or a MOPP4 ensemble encumbered with a ballistic chest plate and overwater survival gear was performed at the United States Army Aeromedical Research Laboratory. The study used a repeated-measures design with 14 aviators flying 4-hour missions in a UH-60 helicopter simulator. Average crew endurance in the MOPP4-hot condition was reduced to one-third of the fully completed mission time of 309 minutes. For the hot condition, core temperature in the simulator rose 1.4 degrees F/hour when aviators wore the encumbered MOPP4 ensemble versus 0.27 degree F/hour when they wore the MOPP0 uniform. Sweating rate in the MOPP4-hot condition was 1,523 ml/hour, resulting in 2.5% dehydration, in contrast to 183 ml/hour and 0.9% dehydration in the MOPP4-cool condition. In this study, pilots flying realistic UH-60 simulator sorties rapidly incurred significant physiological heat strain when wearing an encumbered MOPP4 flight ensemble in hot cockpit conditions.

Adult↗
PubMed1995

The cranial base in obstructive sleep apnea.

PURPOSE: The purpose of this investigation was to determine if there are cranial base differences in adults with obstructive sleep apnea (without identifiable craniofacial abnormalities) when compared with those of adults without airway problems. METHODS: Cephalometric analysis of the cranial base of 52 patients with documented sleep apnea were compared with 96 normal adult patients. Each of the groups was subdivided based on skeletal profiles (Class I, II, III). Cephalometric measurements included cranial base flexure angle and anterior and posterior cranial base lengths. Standard analysis of variance and Students' t test were used to determine level of significance. RESULTS: The cranial base flexure angle in patients with documented sleep apnea was significantly more acute than that found in the nonapnea group. Patients with a skeletal Class III profile had the most acute cranial base flexure whereas those with Class II profiles had the most obtuse angles. This pattern was true for apnea and nonapnea groups. No cranial base length differences could be found in either group. CONCLUSION: The results of this study demonstrate that there were abnormalities of the cranial base in patients with obstructive sleep apnea. Abnormalities of the cranial base seen in "nonsyndrome" obstructive sleep apnea patients are similar to those seen in patients with certain identifiable syndromes. This may suggest that sleep apnea is a reflection of a form of craniofacial syndrome.

Adult↗
PubMed1990

Peptides derived from the CDR3-homologous domain of the CD4 molecule are specific inhibitors of HIV-1 and SIV infection, virus-induced cell fusion, and postinfection viral transmission in vitro. Implications for the design of small peptide anti-HIV therapeutic agents.

Peptides 12-25 amino acids in length from the V1J1 region of the CD4 molecule (residues 1-120) were synthesized as randomly derivatized, deliberately derivatized, or pure peptide products, and tested for their ability to inhibit HIV-1-induced cell fusion, HIV-1 and SIV infection of CD4-positive human cells, HIV-1 envelope glycoprotein binding to the CD4 molecule, CD4-neutralizing antibody binding to the CD4 holoreceptor, and CD4-dependent cellular immune function in the mixed lymphocyte and cytotoxic T-cell bioassays. Only peptides derived from the complementarity-determining region 3 (CDR3)-homologous domain of CD4, in particular CD4(81-92) and CD4(81-101), were effective antiviral agents. Within the CD4(81-92) series, R-group derivatization of selective amino acid residues was an absolute requirement for biological activity. The prototype compound T1C4E5-tribenzyl-K10-acetyl-TYICEVEDQKEE inhibited HIV-1-induced cell fusion at 32 microM, HIV-1 infection of CEM-SS cells at 10 microM, SIV infection of CEM-174 cells at less than 125 microM, gp120/CD4 binding at 60 microM, and postinfection cell-mediated viral transmission at 10-15 microM. Compounds of identical structure and derivatization, but of altered primary sequence, were substantially less active, or without activity, in these assays. These data indicate that the effect of amino acid derivatization of the CD4(81-92) peptide was most likely restriction of the flexible underivatized peptide backbone to a conformation closely approximating that of the CDR3-homologous gp120 binding site of the native CD4 molecule. Peptide antiviral activity was specific, as judged by lack of cytotoxicity, lack of inhibition of HTLV-1-induced cell fusion, and lack of inhibition of CD4-dependent cellular immune function in vitro. Further derivatization of the prototype compound involving the production of cyclic congeners yielded peptides with submicromolar potency to block HIV-1 infection, strengthening the hypothesis that previous peptide derivations accomplished partial restriction of the conformation of CD4(81-92) to one favorable for interaction with gp120. Concentrations of the original prototype compound T1C4E5-tribenzyl-CD4(81-92) that inhibited infection in vitro more than 50% could be achieved for several hours by intravenous infusion in primates and were well-tolerated at these levels. The peptide was not efficacious to inhibit establishment of viral infection at these doses; however, peptide treatment did lower average viral antigenemia and delay the cumulative time to morbidity relative to the control group.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Synthetic CD4 peptide derivatives that inhibit HIV infection and cytopathicity.

Synthetic peptide segments of the CD4 molecule were tested for their ability to inhibit infection of CD4+ cells by the human immunodeficiency virus (HIV) and to inhibit HIV-induced cell fusion. A peptide mixture composed of CD4(76-94), and synthesis side products, blocked HIV-induced cell fusion at a nominal concentration of 125 micromolar. Upon high-performance liquid chromatography, the antisyncytial activity of the peptide mixture was found not in the fraction containing the peptide CD4(76-94) itself, but in a side fraction containing derivatized peptide products generated in the automated synthesis. Derivatized deletion and substitution peptides in the region CD4(76-94) were used to demonstrate sequence specificity, a requirement for benzyl derivatization, and a core seven-residue fragment required for antisyncytial activity. A partially purified S-benzyl-CD4(83-94) peptide mixture inhibited HIV-induced cell fusion at a nominal concentration of less than or equal to 32 micromolar. Derivatized CD4 peptides blocked cell fusion induced by several HIV isolates and by the simian immunodeficiency virus, SIV, and blocked infection in vitro by four HIV-1 isolates with widely variant envelope gene sequences. Purified CD4(83-94) dibenzylated at cysteine 86 and glutamate 87 possessed antisyncytial activity at 125 micromolar. Derivatization may specifically alter the conformation of CD4 holoreceptor peptide fragments, increasing their antiviral efficacy.

Amino Acid Sequence↗
PubMed1988

Partial trisomy 9--further delineation of the phenotype.

A patient with partial trisomy 9 (47,XX,+9pter----q22.1) had bilateral cleft lip and cleft palate, enophthalmos, severe micrognathia, small, apparently low-set ears, and dislocatable knees. The phenotypic findings are compared with those of other documented cases of total trisomy 9.

Abnormalities, Multiple↗
PubMed1985

Aortitis and large vessel arteritis in a newborn.

Disseminated arteritis with extensive involvement of the aorta, as well as involvement of the arch vessels, coronary arteries, and pulmonary arteries, but not of the arteries within the liver, spleen, kidneys, or other organs, is unusual in a newborn. The presence of both acute and chronic inflammation with fibrosis, as well as calcification and focal ossification in the aorta, would suggest that the process had been present for some time before birth. This lesion should be described rather than designated by an eponym or included with such entities as Takayasu's disease. An additional finding of interest was widespread calcification in Bowman's capsules of numerous glomeruli.

Aorta, Thoracic↗
PubMed1983

The effects of surgical procedures on the blood supply to the femoral head.

UNLABELLED: We have studied the effects of surgical procedures on the blood supply to the femoral head in adult dogs. The blood supply to normal adult canine femoral heads and osteoarthritic femoral heads was assessed by microvascular injection techniques and by measurement of the rate of blood flow by the hydrogen-washout technique. Circulation to the femoral head in the mature dog normally is dependent on retinacular vessels. Vascular anastomoses between the epiphysis and the metaphysis are generally not larger than capillary size. Reaming the femoral head does not devascularize the bone unless the retinacular vessels are disturbed. Stripping of the retinaculum, or combined reaming of the femoral head and stripping of the retinaculum, devascularized the femoral head in adult dogs with normal femoral heads. In the osteoarthritic hips, vascular anastomoses developed between the epiphysis and the metaphysis, so that stripping the retinaculum did not devascularize the femoral head. However, the rate of blood flow was decreased after combined reaming and retinacular stripping. CLINICAL RELEVANCE: In the non-arthritic hip or in one with early arthritis, the retinacular vessels are of primary importance to circulation to the femoral head. Damage to these vessels during surgery will lead to osteonecrosis in a high percentage of patients. The formation of vascular anastomoses between the epiphysis and the metaphysis during the development of osteoarthritis may make the arthritic femoral head less vulnerable. However, care should be taken to preserve retinacular vessels, since in this study the rate of blood flow was decreased by reaming the femoral head and stripping the retinaculum.

Animals↗
PubMed1977

The structural basis of rabbit VH allotypes: serologic studies on a1 H chains with defined amino acid sequence.

The amino acid sequences for the VH regions of three homogeneous antibodies elicited by type III pneumococcal vaccine were determined. All three antibodies had the group a allotype a1. Two of the antibody H chains (3372, 3381) had identical amino acid sequences in all framework positions that are considered correlates of the VH allotype, whereas the third H chain (3T72) differed from these at positions 15 and 16. The a1 allotypic specificities of the three homogeneous antibodies were compared by quantitative radiobinding and inhibition assays by using both insolubilized anti-a1 antisera and allotypic antiserum fractions rendered specific for the homogeneous antibody 3374. It was found that antibodies 3374 and 3381 are allotypically indistinguishable and have in common an a1 allotypic specificity that predominates in pooled a1 IgG. The allotypic specificity of the 3T72 antibody, on the other hand, was markedly deficient to those of 3374, 3381, and the a1 IgG pool. This correlation of allotypic difference with amino acid sequence variation at position 15 and 16 of the H chain indicates the involvement of these two residues in a major a1 allotypic determinant.

Amino Acid Sequence↗
PubMed1977

Development of a highly sensitive radioimmunoassay for digoxin and its application in pediatric practice.

The sensitivity of two established routine digoxin radioimmunoassay methods has been increased to enable the provision of a rapid and relatively atraumatic inpatient and outpatient service for neonates and small children, using capillary blood samples obtained by heel-prick. The methods employ 125I- or 3H-labelled digoxin, a rabbit antiserum raised against a digoxin: bovine serum albumin conjugate and only 10 or 25 microliter of plasma as the sample. The results obtained using these highly sensitive assays correlate closely with those found using conventional assays, requiring larger sample volumes. An apparent difference in sensitivity to digoxin has been demonstrated between infants and children more than 1 yr old. Thus infants appear to tolerate plateau phase plasma levels (mean value for non toxic infants 2.6 +/- 1.8 ng/ml) that in older children or adults would be associated with digoxin toxicity.

Binding Sites, Antibody↗