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Biomedical subjects

A Wright

Publications and source records attributed to A Wright.

At least 109 records · Page 6Linked to original sources

Rapid development of genotypic resistance to lamivudine when combined with zidovudine in pregnancy.

The prevention of mother to child transmission of HIV-1 by zidovudine monotherapy is well known, but increasingly combination anti-retroviral therapy is prescribed during pregnancy. In this prospective study, 19 pregnant women with human immunodeficiency virus-1 (HIV-1) infection who elected to take anti-retroviral therapy during the second and third trimesters were treated with zidovudine or zidovudine plus lamivudine. Fourteen women treated with zidovudine monotherapy had a mean 0.3 log(10) reduction in viral load and a mean 52 x 10(6)/L (17%) increase in CD4+ lymphocytes at delivery compared with pre-treatment samples. Genotypic mutations associated with decreased susceptibility to zidovudine were detected in 2 of 10 women at delivery. Five women with more advanced HIV-1 infection were treated with zidovudine plus lamivudine and a mean 1.5 log(10) reduction in viral load together with a mean 30 x 10(6)/L (33%) increase in CD4+ lymphocytes was observed in this group. However, four of five women in the dual therapy arm had the M184V mutation in the reverse transcriptase gene associated with decreased susceptibility to lamivudine at delivery. We conclude that zidovudine plus lamivudine reduced HIV-1 plasma viraemia to low levels in pregnant women with advanced HIV-1 disease but the rapid development of genotypic resistance to lamivudine indicates that additional therapy is required both for the long-term benefit of the mothers and to prevent the development of resistant virus that may be transmitted to the infant.

Adult↗

Laparoscopy with laparoscopic ultrasonography in the TNM staging of pancreatic carcinoma.

A prospective study was performed comparing laparoscopy with laparoscopic ultrasonography (LapUS), transabdominal ultrasonography (USS), computed tomography (CT), and selective visceral angiography with portal phase venography (SVA) for the assessment of resectability in 50 patients with pancreatic or periampullary cancer. The results were stratified by TNM stages. Tumor unresectability was demonstrated in 36 patients (72%). The sensitivity of LapUS for demonstrating the index lesion was 96%. Laparoscopic ultrasonography failed to predict factors precluding resection by T stage in six patients, and there were no significant differences in the ability of any modality to predict local resectability (predictive value 58-73%). Laparoscopic ultrasonography did not overestimate T stage and was significantly more specific for assessing unresectability compared with USS (100% vs. 64%, p<0.05) and CT (100% vs. 47%, p<0.005). No imaging investigation was able to assess the N stage accurately. Metastases were confirmed in 16 patients (32%), with LapUS proving significantly more sensitive than USS (94% vs. 29%, p<0.001) and CT (94% vs. 33%, p<0.005). The addition of LapUS to the laparoscopic examination did not change the M stage in any patient, as all metastases were superficially located. Laparoscopy with LapUS was the most reliable method for assessing overall tumour resectability and was significantly more predictive than CT (97% vs. 79%, p<0.005). These results confirm that laparoscopy is indispensable for detecting occult intraabdominal metastases. LapUS reliably predicts tumor unresectability, offsetting the tendency of USS and CT to overestimate T stage. Methods of accurate N staging remain elusive, and the use of routine SVA is not justified.

Adult↗

The nature of the obstructive muscular bundles in double-chambered right ventricle.

OBJECTIVE: Our goal was to establish the morphologic nature of the obstructive muscular lesions in double-chambered right ventricle. METHODS: We based our morphologic observations on 10 normal hearts and on the surgical findings in 26 patients, aged 0.5 to 24 years, with a mean of 6.9 years (SD 5.8 years). In the normal hearts, we measured the distance from the pulmonary valve to the apex of the right ventricle and from the takeoff of the moderator band to the ventricular apex. From angiograms available in 20 patients, using the frontal view, we then measured the distance from the pulmonary valve to the apex of the right ventricle and from the midpoint of the obstructive lesion to the apex of the right ventricle. This permitted calculations of multiple ratios. RESULTS: In the 10 normal hearts, the moderator band took origin at a mean ratio of 0.48 (SD 0.16) of the ventricular length. On the basis of the angiographic findings, we identified 2 basic forms of double-chambered right ventricle. In 9 patients, the obstructive muscular shelf was positioned low and diagonally across the apical component, with a mean ratio of 0.38 relative to the ventricular length (SD 0.02). In the other 11 patients, the obstructive shelf was high and horizontal, with a mean ratio of 0.27 (SD 0.02). The difference was statistically significant (P =.001). Surgical repair was performed successfully in all 26 patients through a right ventriculotomy. CONCLUSIONS: Double-chambered right ventricle is the consequence of a high or low muscular division of the apical component of the right ventricle. The abnormal muscular bundle probably represents accentuated septoparietal trabeculations, rather than always being an abnormal moderator band.

Adolescent↗

Total serum IgE and its association with asthma symptoms and allergic sensitization among children.

BACKGROUND: Asthma and wheezing during childhood are associated with elevated total serum IgE and with allergic sensitization to local aeroallergens. However, little is known about the longitudinal relationship between total serum IgE and the development of wheezing and allergic sensitization during childhood. OBJECTIVE: The purpose of our investigation was to determine the relationship between total serum IgE and the development of wheezing and allergic sensitization in childhood. METHODS: Our study subjects were participants in the Tucson Children's Respiratory Study who underwent an IgE measurement in at least 1 of 3 surveys (at years 1, 6, and 11) and complete allergy skin tests during the latter 2 surveys. The children's phenotypes were categorized on the basis of skin test response (never, early, and late) and wheezing status (never, early, late, and persistent). Repeated-measures analyses were used, allowing subjects to be included who had unequal numbers of IgE observations (a total of 263 boys and 277 girls). RESULTS: We found that total serum IgE levels track with age: subjects with high serum IgE levels less than 1 year old continued to have high IgE levels at ages 6 and 11 years. Both persistent wheezing and early sensitization were associated with high serum IgE levels at all ages. Boys who had late or persistent wheezing or who were sensitized early or late had high serum IgE levels as early as age 9 months, whereas only girls with persistent wheezing and early sensitization had elevated IgE levels at that age. Children who wheezed only in the first years of life and not after (ie, those with early wheezing) had serum IgE levels that were not different from those of nonwheezing children. CONCLUSION: On the basis of these findings we conclude that although total serum IgE tracks with age, children who are predisposed to persistent wheezing and early sensitization to local aeroallergens already have high levels of IgE at age 9 months. This suggests that the predisposition to respond to environmental stimuli through high levels of IgE precede early allergic sensitization, indicating that there may be a common defect in the development of the immune system involving IgE production and early allergic sensitization.

Asthma↗

The displacement, velocity and frequency profile of the frontal plane motion produced by the cervical lateral glide treatment technique.

OBJECTIVE: To investigate the specificity of linear and angular displacement, peak velocity and frequency of oscillation of the frontal plane motion produced by the lateral glide treatment technique of the cervical spine. DESIGN: A within-subjects design was used. BACKGROUND: The lateral glide treatment technique of the cervical spine has previously been shown to produce specific neurophysiological effects, whereas the technique's biomechanical effects remain uninvestigated. A relationship may exist between a technique's biomechanical effects and its clinical outcome. METHODS: Eight asymptomatic subjects participated in the study. Retroreflective markers were placed dorsally at the occiput, and the C5, T1, T3 and T5 vertebrae. Movement of these markers was recorded by a video processor. The same physiotherapist applied the treatment technique to each subject. RESULTS: Linear displacement (3.336 cm) and peak velocity (13.643 cm/s) between C5 and T1 markers was greater than between T1 and T3, Occiput and C5, and T3 and T5. Angular displacement about C5 (26.5 degrees ) was twice that about T1 and T3, but unlike T1 and T3 occurred in the opposite direction to that of the treatment technique. Frequency of oscillation was 1. 255 Hz. CONCLUSION: The lateral glide treatment technique produced a characteristic ipsilateral displacement rather than side flexion, predominantly at its region of application. RELEVANCE: This study provides the basis for further investigations of the mechanisms of action of the lateral glide treatment technique. It also provides clinicians with guidelines for the application of this technique.

Adolescent↗

Short-term benefits of grommet insertion in children.

It is commonly acknowledged that otitis media with effusion (OME) can cause behavioural disturbances and that this can be relieved by grommet insertion. However, this widely-held perception has not been documented in the literature. In this study parents were asked to complete a short behavioural questionnaire on the day of the admission and 6 weeks later. A total of 32 children admitted to the Day Care Unit for insertion of grommets at The Royal National Throat, Nose and Ear Hospital, London, UK, were recruited. There was a significant behavioural change, evident by the difference in the scores before and after grommet insertion (P < 0.001).

Child↗

An investigation of stress and pain perception during manual therapy in asymptomatic subjects.

Stress perceived by the patient during the application of a manual therapy treatment technique may account for the reported findings of sympathoexcitation and hypoalgesia immediately after its application. This study investigated whether there was a difference in the level of perceived stress and pain before, during and after the application of a treatment condition (treatment, placebo or control technique), or whether the difference related to the time course of subject involvement in the study.Twenty-four asymptomatic subjects participated in a double-blind, placebo-controlled, within-subjects study in which stress was measured with a stress rating scale and a stress visual analogue scale. Pain experienced by the subject during the application of the treatment technique was measured with a visual analogue scale and modified McGill pain questionnaire. There was no effect of the treatment condition on perceived stress, but there was a reduction in stress levels over the time course of involvement in the experiment, as demonstrated by pre-application levels of stress. Pain was not produced by the treatment technique.This study demonstrated that stress and pain were not features of the lateral glide manipulation of the cervical spine in asymptomatic subjects. If the dorsal periaqueductal grey region is responsible for the initial effects of manual therapy, as has been previously suggested, then stress and pain do not appear to play a role in activating this system during the application of a manual therapy treatment technique in asymptomatic subjects. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗

Recent concepts in the neurophysiology of pain.

This paper describes many of the processes that exist for upregulation of the nociceptive system in response to tissue injury. The processes of peripheral and central sensitization are described. Potential interactions between the nociceptive, motor and autonomic systems are considered. The potential for psychosocial factors to influence neuroplasticity within the nociceptive system is also discussed.

Animals↗

Evidence of avian leukosis virus subgroup E and endogenous avian virus in measles and mumps vaccines derived from chicken cells: investigation of transmission to vaccine recipients.

Reverse transcriptase (RT) activity has been detected recently in all chicken cell-derived measles and mumps vaccines. A study of a vaccine manufactured in Europe indicated that the RT is associated with particles containing endogenous avian retrovirus (EAV-0) RNA and originates from the chicken embryonic fibroblasts (CEF) used as a substrate for propagation of the vaccine. We investigated the origin of RT in measles and mumps vaccines from a U.S. manufacturer and confirm the presence of RT and EAV RNA. Additionally, we provide new evidence for the presence of avian leukosis virus (ALV) in both CEF supernatants and vaccines. ALV pol sequences were first identified in particle-associated RNA by amplification with degenerate retroviral pol primers. ALV RNA sequences from both the gag and env regions were also detected. Analysis of hypervariable region 2 of env revealed a subgroup E sequence, an endogenous-type ALV. Both CEF- and vaccine-derived RT activity could be blocked by antibodies to ALV RT. Release of ALV-like virus particles from uninoculated CEF was also documented by electron microscopy. Nonetheless, infectivity studies on susceptible 15B1 chicken cells gave no evidence of infectious ALV, which is consistent with the phenotypes of the ev loci identified in the CEF. PCR analysis of ALV and EAV proviral sequences in peripheral blood mononuclear cells from 33 children after measles and mumps vaccination yielded negative results. Our data indicate that the sources of RT activity in all RT-positive measles and mumps vaccines may not be similar and depend on the particular endogenous retroviral loci present in the chicken cell substrate used. The present data do not support transmission of either ALV or EAV to recipients of the U.S.-made vaccine and provide reassurance for current immunization policies.

Animals↗

Difference between RP2 and RP3 phenotypes in X linked retinitis pigmentosa.

AIM: X linked retinitis pigmentosa (XLRP) has two genetic loci known as "RP2" and "RP3". Clinical features reported to differentiate RP2 from RP3 include a higher prevalence of myopia and primary cone dysfunction in RP2, and late onset night blindness and tapetal reflex in RP3. Members from 14 XLRP families were examined in an attempt to verify these differences. METHODS: 16 affected males and 37 females from 14 XLRP families assigned as either RP2 or RP3 by haplotype analysis and/or by heterogeneity analysis were examined. Members of all 14 families who were willing to participate but unavailable for examination were contacted and detailed interviews carried out. RESULTS: No clear phenotypic differences were found that could be used to reliably differentiate RP2 from RP3 with respect to myopia and onset of night blindness. The tapetal reflex was also found to be present in carriers of both RP2 and RP3. CONCLUSIONS: XLRP is a heterogeneous class of rod degenerative disorders with no clear phenotypic differentiation between the two genetic loci RP2 and RP3. There is a continuum of clinical presentations which can be seen in both RP2 and RP3, but the features within a given family tend to be consistent. However, interfamilial variability is prevalent leading to a wide range of clinical presentations and more than one abnormal allele at each gene locus cannot be excluded.

Adult↗

Intra-operative localisation of skull base tumours. A case report using the ISG viewing wand in the management of trigeminal neuroma.

Deep-seated skull base tumours provide as much a challenge to the surgeons' skills of localisation as to his technical abilities during the resection. These lesions are frequently inaccessible and lie adjacent to vital structures requiring extensive cerebral retraction for adequate exposure and direct visualisation. The ISG viewing wand is a newly developed image guidance system to aid direction of the operative approach and localisation of intracerebral pathology. We discuss its use in the management of a trigeminal neuroma.

Cranial Nerve Neoplasms↗

The occult pneumothorax: an increasing diagnostic entity in trauma.

The increasing use of CT for the evaluation of blunt abdominal trauma has diagnosed undetected pneumothoraces in many patients. We performed a retrospective study at a major trauma center to determine the incidence of occult pneumothorax in the trauma patient. All trauma patients (3121) admitted to a Level I trauma center over a 51-month period were reviewed to determine the incidence of pneumothorax and occult pneumothorax, the method of diagnosis, and treatment. All major trauma patients received a chest X-ray (CXR), whereas 842 patients (27%) underwent an abdominal CT scan. In the 172 patients diagnosed with pneumothorax, 157 abdominal CT scans were performed and 143 were positive for pneumothorax. CXR revealed 49 right-sided pneumothoraces and 58 left-sided pneumothoraces in 95 patients. Abdominal CT scans diagnosed 73 right pneumothoraces and 90 left pneumothoraces in 143 patients. There were 67 patients (71 thoraces) who were seen to have a pneumothorax on abdominal CT scan not seen on admission CXR. This represents 2.2 per cent of all trauma patients and 7.9 per cent of patients with abdominal CT scans. In looking at just trauma patients with pneumothorax, the CT scan was responsible for diagnosing 39 per cent of the patients with a pneumothorax. The occult pneumothorax is being diagnosed more frequently as methods of evaluating and diagnosing trauma patients become more sensitive.

Abdominal Injuries↗

The use of infrared spectrophotometry for measuring body water spaces.

BACKGROUND: The conventional method of measuring total body water by the deuterium isotope dilution method uses gas isotope ratio mass spectrometry (IRMS), which is both expensive and time-consuming. We investigated an alternative method, using Fourier transform infrared spectrophotometry (FTIR), which uses less expensive instrumentation and requires little sample preparation. METHOD: Total body water measurements in human subjects were made by obtaining plasma, saliva, and urine samples before and after oral dosing with 1.5 mol of deuterium oxide. The enrichments of the body fluids were determined from the FTIR spectra in the range 1800-2800 cm-1, using a novel algorithm for estimation of instrumental response, and by IRMS for comparison. RESULTS: The CV (n = 5) for repeat determinations of deuterium oxide in biological fluids and calibrator solutions (400-1000 micromol/mol) was found to be in the range 0.1-0.9%. The use of the novel algorithm instead of the integration routines supplied with the instrument gave at least a threefold increase in precision, and there was no significant difference between the results obtained with FTIR and those obtained with IRMS. CONCLUSION: This improved infrared method for measuring deuterium enrichment in plasma and saliva requires no sample preparation, is rapid, and has potential value to the clinician.

Body Water↗

Drug monitoring of antiretroviral therapy for HIV-1 infection: method validation and results of a pilot study.

BACKGROUND: Antiretroviral therapy for HIV-1 infection has become increasingly complex. The availability of new and potent drugs and progress in understanding the pathogenesis of HIV-1 infection have led to the establishment of new treatment paradigms. The varying dosing regimens, associated toxicities, and the potential for drug-drug and food-drug interactions further complicate treatment. This complexity contributes to patient nonadherence. Because clinicians have no tools to monitor adherence or drug-drug interactions and because response requires that therapy exceed the known inhibiting concentration, serum monitoring of antiretroviral therapy may play a role in improving treatment of HIV-1 infection. We report methods to quantify serum concentrations of antiretroviral drugs used to treat HIV-1 infection, precision and interference studies of these methods, and results observed in a pilot evaluation of blood serum concentrations from 12 human subjects. METHODS: HPLC offers adequate sensitivity to measure peak or trough serum concentrations of delavirdine, lamivudine, nevirapine, indinavir, nelfinavir, ritonavir, and saquinavir and peak serum concentrations of stavudine, zidovudine, and didanosine with reasonable precision. RESULTS: Peak indinavir serum concentrations in most patients were in the range of 1-10 mg/L, and trough concentrations were in the range of 0.1-0.5 mg/L. Peak stavudine concentrations were in the range of 0.3-1.3 mg/L, and trough concentrations were in the range of 0.1-0.5 mg/L. Peak zidovudine concentrations were in the range of 0.1-1.1 mg/L. CONCLUSIONS: Because this was a blood serum concentration-seeking pilot study to evaluate analytic performance, we do not report on the correlation of drug response to blood concentration. However, the concentrations observed in patients are generally consistent with blood concentrations reported from studies of monotherapy.

Anti-HIV Agents↗

Adding Alzheimer's. The industry targets a growing market.

The gaga, go-go early boom may be over for assisted living, but life most definitely goes on for owners and operators. True, money isn't as easy to come by as it once was, as Wall Street analysts and financiers worry about overbuilding and the quality of earnings. The competition is getting more intense and savvier daily. Fill-up time has lengthened, especially in secondary markets where barriers to entry are low. Most of the affluent suburbs that showed up in everybody's initial feasibility studies are now saturated with high-end assisted living facilities. And the capital crunch has turned many cash-strapped developers into eager sellers. But consumer demand keeps growing, and the demographics look even brighter 10 or 20 years down the line. The trick is to find new ways to distinguish yourself from your competition--and, perhaps, to attract financing. In this year's special section, we suggest several ways of accomplishing both of those goals.

Aged↗