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Biomedical subjects

T J Butler

Publications and source records attributed to T J Butler.

At least 37 records · Page 2Linked to original sources

How reliable are ultrasound measurements of renal length in adults?

Ultrasound assessment of patients with renal impairment commonly includes measurement of bipolar renal length. Reduction in length is considered to indicate chronic renal disease and is a factor in deciding whether to proceed to renal biopsy. To date, no published data are available on interobserver and intraobserver variation in sonographic renal length measurement in adults. Bilateral renal lengths were measured in 20 adult subjects, with no history of renal disease, by three experienced operators, on two separate occasions. Limits of agreement for replicate measurements by each ultrasonographer and for replicate measurements by each pair of ultrasonographers were determined. Values of repeatability (a measure of intraobserver variation) and reproducibility (a measure of interobserver variation) were calculated for all renal length measurements, and for right and left renal lengths separately. Results indicate that replicate renal length measurements differ by less than 1.85 cm in 95% of cases, and the magnitude of variations is similar when measurements are made by either single or different ultrasonographers, and are similar for right and left renal length measurements. This suggests that sonographic bipolar renal length measurements in normal adult kidneys are reasonably reliable. In diseased kidneys, however, in which identification of renal poles is difficult, interobserver and intraobserver variation may be much greater.

Adult↗

Mitotic activity during preimplantation development of human embryos.

The rate of cell division of human embryos in vitro was estimated throughout the preimplantation period. Seventy-five human embryos were assessed by performing nuclei counts on whole mount preparations at 24 h intervals between day 2 and day 6 of development. The results indicate that the cell doubling time increases after the first two division cycles. The mean (+/- SEM) doubling time between day 2 and day 6 was 31 +/- 2.51 h. At the end of the designated culture periods, embryos were exposed to a microtubule disrupting agent, which caused the nuclei to arrest in metaphase. Thus, a profile of the mitotic activity at given stages of development was obtained. The numbers of actively dividing cells were frequently lower than anticipated, indicating that nuclei counts cannot be directly correlated with continuing mitotic activity.

Blastocyst↗

Intake of non-starch polysaccharide (dietary fibre) in edentulous and dentate persons: an observational study.

Compromised masticatory efficiency places edentulous persons at risk of consuming a diet low in non-starch polysaccharide (NSP) ('dietary fibre'). No study has quantified NSP intake in edentulous people using a valid and reliable method of dietary assessment. The aim of this study was to provide quantitative data on NSP intake of edentulous persons, together with information on its dietary sources. Using the dietary history method, habitual intake of NSP was compared between edentulous persons (n = 30) and dentate persons (n = 30) between the ages of 40 and 60. Groups were matched for sex and social class. The edentulous group had a median NSP intake of 73 (31-211) g/week. This was significantly lower than that of the dentate group of 106 (25-225) g/week (P = 0.014). Neither group completely met current UK guidelines. NSP intake of 56% (n = 17) of the edentulous group was below 84 g/week, whilst 17% (n = 5) of the dentate group was below this figure--a level of intake below which increased occurrence of gastrointestinal complaints has been observed. The dentate group obtained significantly more NSP from all rich sources, including wholemeal breads, cereals, vegetables and fruit. Depending on their form and preparation, such foods are not necessarily difficult to chew. Specific advice on food selection is required to ensure the edentulous patient has an adequate intake of NSP. Education of the dentist for this purpose is of paramount importance.

Adult↗

Selective heparinization of the extracorporeal membrane oxygenation circuit using continuous infusions of protamine and heparin in a short-term pig model.

Systemic heparinization is required for both neonatal and paediatric extracorporeal membrane oxygenation (ECMO). However, it places the patient at risk of serious haemorrhage. We report an alternative: 'selective' heparinization of the ECMO circuit using a continuous infusion of heparin near the venous catheter as blood enters the circuit, and a simultaneous protamine infusion near the arterial catheter as blood enters the patient. Theoretically, the circuit remains heparinized while the patient maintains near-normal clotting activity. Three healthy piglets were placed on venoarterial ECMO in standard fashion. When the animal and its extracorporeal circuit flow were stable, a protamine infusion was begun: 1 mg of protamine to neutralize each 100 units of infused heparin. No haemodynamic instability was noted during the five hours of each study. Mean activated clotting times (ACT) were significantly lower in all three piglets than in their respective circuits (p < 0.001). We conclude that 'selective' heparinization of the ECMO circuit is possible using continuous infusions of protamine and heparin in a short-term piglet model.

Animals↗

The safety of emergency neuromuscular blockade and orotracheal intubation in the acutely injured trauma patient.

BACKGROUND: This study was done to determine the safety and success of orotracheal intubation with planned neuromuscular blockade in patients who are severely injured. The study was performed at Carle Foundation Hospital, designated Level I trauma center located in east central Illinois. STUDY DESIGN: A retrospective review of the trauma registry and medical records of all patients requiring emergency airway control from September 1, 1987 to September 30, 1991 was performed. Two hundred twenty-nine patients who were critically injured were reviewed, the mean injury severity score was 29 (range of 3 to 75), the mean revised trauma score was 9 (range of 3 to 12), the mean Glasgow Coma Scale was 9 (range of 3 to 15), and the mean age was 31 years (range of one to 94 years). RESULTS: Indications for intubation included hemodynamic instability or altered level of consciousness (66.4 percent), or both, combative or uncooperative behavior (33.2 percent), and need to secure airway for transport (0.4 percent). Two hundred twenty-three (97.4 percent) patients were successfully intubated. Six (2.6 percent) patients required cricothyroidotomy and one (0.4 percent) patient was aspirated during intubation. Eight (3.5 percent) patients had cervical spine injuries but had no complications from orotracheal intubation. In the combative group, 32 (42 percent) patients had significant head injuries and 17 (22 percent) had other potentially life-threatening injuries. CONCLUSIONS: Orotracheal intubation with planned neuromuscular blockade and in-line cervical traction is a safe, effective method for airway control in patients who are severely injured. This technique is also indicated to expedite therapy in combative, uncooperative patients because of the high incidence of significant life-threatening injuries to the brain and other organs.

Adolescent↗

Demonstration of direct xenorecognition of porcine cells by human cytotoxic T lymphocytes.

It is not known whether human cytotoxic T cells can recognize porcine major histocompatibility antigens directly, or whether recognition occurs by co-operation with syngeneic human antigen-presenting cells (APC). Limiting dilution assays were used to quantify human anti-pig precursor cytotoxic T-cell (CTLp) frequencies and to analyse the 'kinetics' of the interaction between human lymphoid cells and porcine splenic cells. Single-hit kinetics are demonstrative of direct recognition, as only one cell type, the CTLp, is diluted out, whereas multi-hit kinetics indicate that more than one cell is limiting and provide evidence for co-operative recognition of xenoantigens. Initial assays indicated that the frequency of CTLp reactive with alloantigens on human splenic targets (mean 1/1845; n = 3) was approximately sixfold greater than the frequency of CTLp reactive with porcine splenic cells (1/12,082; n = 3). However, not all of the assays performed using the xenogeneic combination produced single-hit kinetics. Subsequent assays were performed by mixing limiting numbers of human peripheral blood mononuclear cells (PBMC) or APC-depleted PBMC preparations with porcine splenocytes. There was a significant difference in the frequency of xenospecific CTLp between PBMC and APC-depleted preparations (P = 0.034). The overall frequency increased in the APC-depleted group. Variation between the seven human donors was also significant (P = 0.006). There was no significant difference in frequency between the two cell preparations after correction for the proportion of CD3+ cells (P = 0.13). There was, however, a significant departure from single-hit kinetics in the PBMC group (P = 0.004) which was not observed in the APC-depleted group (P = 0.052). It is concluded that human cytotoxic T cells can be activated by porcine xenoantigens directly. However, the direct recognition mechanism can be altered in the presence of human APC.

Animals↗

QT prolongation and sudden cardiac death in patients with alcoholic liver disease.

Cardiovascular death is the most important cause of mortality in alcoholics, yet alcohol may protect against ischaemic heart disease. This could be explained if deaths were a consequence of alcohol-related arrhythmias rather than of coronary atheroma. In many conditions, abnormalities of the QT interval are markers of arrhythmia and for risk of sudden death. We examined the relation between QT intervals and mortality in patients with alcoholic liver disease. Simultaneous 12-lead electrocardiographic recordings were obtained from 69 patients with histologically proven alcoholic liver disease (without evidence of structural heart disease), and from 40 healthy non-drinking controls matched for age and sex. Patients were abstinent for at least 7 days before investigation to exclude acute effects of alcohol. QT intervals were corrected for rate with Bazett's and cube root formulae to define QTc and QTcub, respectively. Unlike QTc, QTcub was independent of rate. Patients were followed for up to four years. For those who died, the cause was determined from case records and postmortem reports. Maximum QT intervals were longer in alcoholics than in controls (QTcub 450 vs 439, p = 0.016). This difference was not explained by variations in electrolytes. QT intervals were prolonged in the 14 patients who died compared with survivors (QTcub 471 vs 446, p = 0.007). This difference was mainly due to the long QT intervals in the 6 patients with sudden cardiac deaths (QTcub 493). The only other factor independently associated with death was sex. QT interval prolongation occurs in some patients with alcoholic liver disease and is associated with an adverse prognosis, especially sudden cardiac death. QT measurement should be included in the initial assessment of alcoholic patients, particularly in those considered for liver transplantation.

Adult↗

Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 1. Trends across the clinical groups.

This multidisciplinary study was undertaken to record the variation in gene and protein expression in a large cohort of patients with well defined clinical phenotypes. The patients, whose ages ranged from 4 years to 66 years, spanned a wide range of disease severity. They represented the first 100 patients who had been examined in Newcastle, had undergone a muscle biopsy, and provided a blood sample for DNA analysis. The study had three aims: to observe any trends in the analyses across the clinical groups, to correlate gene and protein expression in individual patients, and to use the data collected to assess the relative usefulness of different techniques in the diagnosis and prognosis of patients with Duchenne and Becker dystrophy (DMD/BMD). In part 1, we describe the clinical assessment of the patients and the trends that were observed across the cohort. The patients were divided into seven groups. Group 1 had severe DMD (n = 21), group 2 had milder DMD (n = 20), group 3 were intermediate D/BMD patients (n = 9), group 4 had severe BMD (n = 5), and group 5 were more typical BMD patients (n = 31). Some patients were too young to be classified (n = 7) and a group of all the female patients were also classified separately (n = 7). The number of DMD and BMD patients was about equal, in accord with disease prevalence in the north of England, but an unusually high proportion were sporadic cases. Dystrophin labelling (performed with up to three antibodies) on both blots and sections increased gradually across the clinical groups. All histopathological indices, except the proportion of fat in biopsy sections, showed clear trends across the groups.

Adolescent↗

Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 2. Correlations within individual patients.

This report is the second part of a trilogy from a multidisciplinary study which was undertaken to record the relationships between clinical severity and dystrophin gene and protein expression. The aim in part 2 was to correlate the effect of gene deletions on protein expression in individual patients with well defined clinical phenotypes. Among the DMD patients, most of the deletions/duplications disrupted the open reading frame, but three patients had in frame deletions. Some of the intermediate D/BMD patients had mutations which were frameshifting while others were in frame. All of the deletions/duplications in the BMD patients maintained the open reading frame and 25/26 deletions in typical BMD group 5 started with exon 45. The deletion of single exon 44 was the most common mutation in patients from groups 1 to 3. Dystrophin was detected in sections and blots from 58% of the DMD patients with a size that was compatible with synthesis from mRNA in which the reading frame had been restored. Certain deletions were particularly associated with the occurrence of limited dystrophin synthesis in DMD patients. For example, 9/11 DMD patients missing single exons had some detectable dystrophin labelling compared with 10/24 who had deletions affecting more than one exon. All patients missing single exon 44 or 45 had some dystrophin. Deletions starting or finishing with exons 3 or 51 (8/9) cases were usually associated with dystrophin synthesis whereas those starting or finishing with exons 46 or 52 (11/11) were not. Formal IQ assessments (verbal, performance, and full scores) were available for 47 patients. Mean IQ score among the DMD patients was 83 and no clear relationship was found between gene mutations and IQ. The mutations in patients with a particularly severe deficit of verbal IQ were spread throughout the gene.

Adolescent↗

Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 3. Differential diagnosis and prognosis.

This report is the third part of a trilogy from a multidisciplinary study which was undertaken to investigate gene and protein expression in a large cohort of patients with well defined and diverse clinical phenotypes. The aim of part 3 was to review which of the analytical techniques that we had used would be the most useful for differential diagnosis, and which would provide the most accurate indication of disease severity. Careful clinical appraisal is very important and every DMD patient was correctly diagnosed on this basis. In contrast, half of the sporadic BMD patients and all of the sporadic female patients had received different tentative diagnoses based on clinical assessments alone. Sequential observations of quantitative parameters (such as the time taken to run a fixed distance) were found to be useful clinical indicators for prognosis. Intellectual problems might modify the impression of physical ability in patients presenting at a young age. Histopathological assessment was accurate for DMD but differentiation between BMD and other disorders was more difficult, as was the identification of manifesting carriers. Our data on a small number of women with symptoms of muscle disease indicate that abnormal patterns of dystrophin labelling on sections may be an effective way of differentiating between female patients with a form of limb girdle dystrophy and those carrying a defective Xp21 gene. Dystrophin gene analysis detects deletions/duplications in 50 to 90% of male patients and is the most effective non-invasive technique for diagnosis. Quantitative Western blotting, however, would differentiate between all Xp21 and non-Xp21 male patients. In this study we found a clear relationship between increased dystrophin abundance (determined by densitometric analysis of blots) and clinical condition, with a correlation between dystrophin abundance and the age at loss of independent mobility among boys with DMD and intermediate D/BMD. This indicates that blotting is the most sensitive and accurate technique for diagnosis and prognosis.

Adolescent↗

The effect of acute pharmacological manipulation of central serotonin neurotransmission on osmoregulated secretion of arginine vasopressin in the rat.

To explore the hypothesis that serotonin (5-HT) is important in osmoregulated arginine vasopressin (AVP) secretion, we administered (i.p.) fluoxetine (FL) a 5-HT reuptake inhibitor (10 mg/kg body weight), ritanserin (RIT), an antagonist at the 5-HT2 and 5-HT1c receptor subtypes (1 mg/kg body weight), 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI), a 5-HT2 receptor agonist (1 mg/kg body weight) or vehicle to rats 30 min before they were given an osmotic challenge. Rats received distilled water, normotonic saline (150 mmol NaCl/l) or hypertonic saline (500 mmol NaCl/l) (20 mg/kg i.p.) and were killed 30 min later. The osmotic stimulus alone produced significant (P < 0.001) effects on plasma osmolality and plasma sodium but FL, RIT and DOI did not have any significant effect on this stimulus. FL had no significant effect on the osmotic threshold of AVP release but significantly (P < 0.001) increased basal AVP secretion from 1.6 +/- 1.0 to 3.1 +/- 1.3 (S.E.M.) pmol AVP/l and significantly (P < 0.001) increased the AVP response to changes in plasma osmolality: vehicle-treated, 0.7 +/- 0.4; FL-treated, 1.7 +/- 0.2 pmol AVP/l per mOsm per kg. Neither RIT nor DOI had any significant effect on basal or stimulated AVP secretion. In a second study, RIT was administered 60 min i.p. prior to FL i.p. (doses as above), which was followed 30 min later by a hypertonic stimulus i.p. and rats were killed 30 min after hypertonic saline treatment. RIT had no significant effect on the AVP response to plasma osmolality and did not significantly alter the FL-augmented AVP response, suggesting that neither the 5-HT2 nor the 5-HT1c receptors are involved in the response of AVP to FL. We conclude that FL modulates osmoregulated AVP secretion but that the mechanism of this is unknown and is apparently not through the 5-HT2 or 5-HT1c receptor subtypes.

Amphetamines↗

The '90s paradigm shift for electronic claims.

In the development of any new industry, certain events signal a paradigm shift. Those affected by the "new way" finally seem to grasp that change is inevitable. The paradigm shift has begun for electronic claims submission.

Centers for Medicare and Medicaid Services, U.S.↗

Plasma osmolality, iodine concentration and urographic images following high and low osmolar contrast media.

Three contrast media (sodium iothalamate, iopamidol and sodium/methylglucamine ioxaglate) in a dose of 240 mg iodine per kilogram of body weight were compared in clinical urography. The ionic monomer sodium iothalamate was the only medium to significantly elevate the plasma osmolality though it returned to normal values within 4 min. All three media exhibited first order linear kinetics. When corrected for the effects of diuresis, sodium iothalamate was shown to give the highest urinary iodine concentrations. On visual scoring sodium iothalamate produced better nephrograms and overall urograms than either of the low osmolar agents.

Contrast Media↗