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Biomedical subjects

J Tucker

Publications and source records attributed to J Tucker.

At least 19 recordsLinked to original sources

UK neonatal intensive care services in 1996. On behalf of the UK Neonatal Staffing Study Collaborative Group.

A census of activity and staff levels in 1996 was conducted in UK neonatal units and achieved a 100% response from 246 units. Among the 186 neonatal intensive care units, the median (interquartile range) number of total cots was 18(14-22); level 1 intensive care cots 4(2-6); total admissions 318(262-405); very low birthweight admissions 40(28-68); and the number ventilated or given CPAP by endotracheal tube 52(32-83). Forty six (25%) intensive care units lacked the recommended minimum of one consultant with prime responsibility for neonatal medicine. As a conservative estimate 79% of intensive care units had a lower nursing provision than that recommended in previously published guidelines. There was substantial variation in activity and staffing levels among units.

Hospital Bed Capacity

ST segment elevation and the prediction of hospital life-threatening complications: the role of right ventricular and posterior leads.

UNLABELLED: Accurate prognosis in suspected acute myocardial infarction (AMI) is essential for appropriate use of thrombolytic therapy and primary angioplasty. However, previous models may be limited because the 12-lead electrocardiogram (ECG) does not examine the right ventricular (RV) and posterior myocardium. We evaluated ST segment elevation (STSE) in posterior (V7-V9) and RV (V4R-V6R) leads to determine their predictive value for hospital life-threatening complications (HLTCs). METHOD AND RESULTS: This prospective trial of seven Midwestern hospital emergency departments (EDs) had inclusion criteria of age 35 years, chest pain suggestive of ischemia, and coronary care unit (CCU) admission. ECG leads were test positive if STSE was > 0.1 mV. Patients were positive for HLTCs if ED or inpatient hospital course included: ventricular fibrillation or tachycardia, second- or third-degree block, shock, arrest, or death. Univariate and multivariate analyses were performed to test each lead's association with HLTCs. Of 533 patients, 64.7% (345/533) had AMI and 15.8% (85/533) had HLTCs. The sensitivity of 18 leads for HLTCS was increased by 5.8%, but specificity decreased by 8.2%. ECG subgroups by STSE were associated with the following HLTC rates: inferior/+RV (32.4%); anterior (29.5%), lateral (23.1%), inferior RV (17.9%), and posterior (16.2%). V1 (odds = 3.2) and V6R (odds = 3.1) were statistically significant independent predictors. CONCLUSION: Posterior and RV leads did not increase the ECG's overall prognostic value, but in the presence of inferior STSE, were associated with low and high complication rates, respectively. Right and left precordial leads were the best predictors of HTLCs.

Adult

Use of a two-color genetic screen to identify a domain of the global regulator Lrp that is specifically required for pap phase variation.

The global regulator Lrp plays a central role as both a repressor and an activator in Pap phase variation. Unlike most other members of the Lrp regulon such as ilvIH, activation of papBA transcription requires the coregulator PapI and is methylation dependent. We developed a two-color genetic screen to identify Lrp mutations that inhibit Pap phase variation but still activate ilvIH transcription, reasoning that such mutations might identify PapI binding or methylation-responsive domains. Amino acid substitutions in Lrp at position 126, 133, or 134 greatly reduced the rate of Pap switching from phase off to phase on but had much smaller effects on ilvIH transcription. In vitro analyses indicated that the T134A and E133G Lrp variants maintained affinities for pap and ilvIH DNAs similar to those of wild-type Lrp. In addition, both mutant Lrp's were as responsive to PapI as wild-type Lrp, evidenced by an increase in affinity for pap Lrp binding sites 4, 5, and 6. Thus, in vitro analyses did not reveal the step(s) in Pap phase variation where these Lrp mutants were inhibited. In vivo analyses showed that both the T134A and E133G Lrp mutants activated transcription of a phase-on-locked pap derivative containing a mutation in Lrp binding site 3. Further studies indicated that the T134A Lrp mutant was blocked in a step in Pap phase variation that does not involve PapI. Our data suggest that these mutant Lrp's are defective in a previously unidentified interaction required for the switch from the phase-off to the phase-on pap transcription state.

Amino Acid Sequence

Value of posterior and right ventricular leads in comparison to the standard 12-lead electrocardiogram in evaluation of ST-segment elevation in suspected acute myocardial infarction.

In this multicenter prospective trial, we studied posterior (V7 to V9) and right ventricular (V4R to V6R) leads to assess their accuracy compared with standard 12-lead electrocardiograms (ECGs) for the diagnosis of acute myocardial infarction (AMI). Patients aged >34 years with suspected AMI received posterior and right ventricular leads immediately after the initial 12-lead ECG. ST elevation of 0.1 mV in 2 leads was blindly determined and inter-rater reliability estimated. AMI was diagnosed by World Health Organization criteria. The diagnostic value of nonstandard leads was determined when 12-lead ST elevation was absent and present and multivariate stepwise regression analysis was also performed. Of 533 study patients, 64.7% (345 of 533) had AMI and 24.8% received thrombolytic therapy. Posterior and right ventricular leads increased sensitivity for AMI by 8.4% (p = 0.03) but decreased specificity by 7.0% (p = 0.06). The likelihood ratios of a positive test for 12, 12 + posterior, and 12 + right ventricular ECGs were 6.4, 5.6, and 4.5, respectively. Increased AMI rates (positive predictive values) were found when ST elevation was present on 6 nonstandard leads (69.1%), on 12 leads only (88.4%), and on both 6 and 12 leads (96.8%; p <0.001). Treatment rates with thrombolytic therapy increased in parallel with this electrocardiographic gradient. Logistic regression analysis showed that 4 leads were independently predictive of AMI (p <0.001): leads I, II, V3, V5R; V9 approached statistical significance (p = 0.055). The standard ECG is not optimal for detecting ST-segment elevation in AMI, but its accuracy is only modestly improved by the addition of posterior and right ventricular leads.

Aged

Quantitative evaluation of neurotensin receptor purification by immobilized metal affinity chromatography.

Immobilized metal affinity chromatography has recently been used for purification of histidine-tagged membrane proteins in the presence of detergents with varying success. Strong binding to the metal resin is essential for purification when expression levels are low. We have investigated the influence of tag length and type of detergent on the purification of a neurotensin receptor fusion protein expressed in Escherichia coli at a level of about 0.1% of membrane protein. Receptors with six C-terminal histidine residues did not bind to nickel resin in the presence of the anionic detergent sodium dodecyl sulfate. In contrast, partial purification assessed by densitometry of Coomassie-stained gels was achieved using the nonionic detergents dodecyl maltoside or Triton X-100 (53% pure), or a detergent mixture containing the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (46% pure). Linking a highly charged epitope tag to the histidine tail did not affect the nickel-binding properties of receptors. The level of purification was substantially improved (72% pure) by extending the histidine tail to 10 residues because this allowed stringent washes at high imidazole concentration to remove nonspecifically bound contaminants. This strategy not only resulted in efficient purification of receptors from crude membranes, but also worked particularly well for single-step purification from total cell lysates, resulting in 340-fold purification of functional neurotensin receptor.

Chromatography, Affinity

Using willingness to pay to value alternative models of antenatal care.

Recent years have seen the development of different models of antenatal care, especially for low risk women. More specifically, there has been a move for more general practitioner and midwifery involvement in such care. Given the current changes that are taking place in the provision of antenatal care, it is becoming increasingly important to carry out economic evaluations of alternative models of care. This paper applies the economic instrument of willingness to pay to assess the benefits of two alternative forms of antenatal care: general practitioner/midwife routine led care versus obstetrician led care. The results suggest a willingness to pay of pounds 2500 for antenatal care, with no significant difference between the types of care provided. It is concluded that before firm policy conclusions can be reached, further studies should be undertaken to address methodological issues around the willingness to pay technique.

Adult

Delphian lymph node in laryngeal carcinoma: a whole organ study.

The incidence of Delphian or cricothyroid lymph node involvement in laryngeal carcinoma was studied in whole organ sections of 92 laryngectomy specimens. Histologic examination revealed that of the 92 whole organ sections, 8 were noted to have cricothyroid node involvement (8.7%). All 8 patients had submucosal involvement of the conus elasticus, 7 had involvement of the subglottic mucosa, and 6 had invasion of the cricoid cartilage. Four of the 8 patients with cricothyroid node involvement died of the disease, 3 of whom had stomal recurrence. None of the patients who died of disease had surgical management of the paratracheal lymph nodes or postoperative radiation therapy. The benefit of surgical margins of the paratracheal lymph node bed as well as the role of radiation therapy are discussed.

Carcinoma

DNA measurement of overlapping cell nuclei in thick tissue sections.

The paper describes an improved image analysis procedure for measuring the DNA content of cell nuclei in thick sections of liver tissue by absorption densitometry. Whereas previous methods only permitted the analysis of isolated nuclei, the new technique enables both isolated and overlapping nuclei to be measured. A 3D segmentation procedure determines whether each object is an isolated nucleus or a pair of overlapping nuclei; in the latter case the combined optical density is redistributed to the individual nuclei. A selection procedure ensures that only complete nuclei are measured. The method has been tested on specially-prepared Feulgen-stained 20micro sections of normal liver tissue. The overall distribution of the nuclear DNA measurements shows well-defined diploid and tetraploid peaks, with coefficient of variations of less than 10%. Similar distributions were obtained from both the isolated nuclei and overlapped nuclei sub-populations.

Cell Nucleus

Thyroid hormones and cytogenetic outcomes in backpack sprayers using ethylenebis(dithiocarbamate) (EBDC) fungicides in Mexico.

Ethylenebis(dithiocarbamate) (EBDC) fungicides are used heavily in the United States. EBDCs (e.g., mancozeb, maneb) are metabolized to ethylene thiourea (ETU). The EPA classifies ETU as a carcinogen, based on thyroid and other cancers in rodents, and has restricted the use of EBDCs, while requiring workers to use protective equipment. There are no data on the potential carcinogenicity of EBDCs in humans, and there is only one study on human genotoxicity. ETU is known to cause decreases of thyroxine (T4) and increases in thyroid-stimulating hormone (TSH) in rodents. We have studied cytogenetic outcomes and serum thyroid hormone levels among 49 heavily exposed workers without protective equipment spraying EBDC on tomatoes in Mexico. We also studied 14 lightly exposed landowners and 31 nonexposed controls. Urinary ETU was used to compare exposure between groups. We found an increase in TSH (p = 0.05) among applicators compared to controls, but no decrease in thyroid hormone (T4). We found increases in sister chromatid exchange (p = 0.03) and in chromosome translocations (chromosome aberrations that persist through cell division) for applicators compared to controls (p = 0.05). However, the subset of reciprocal translocations showed a lesser increase (p = 0.24). Our data suggest that EBDCs affect the thyroid gland and the lymphocyte genome among heavily exposed workers. However, our data are limited to subclinical outcomes, are of borderline statistical significance, and should be interpreted with caution.

Adult

Eosinophilic colitis presenting as a left-sided colocolonic intussusception with secondary large bowel obstruction: an uncommon entity with a rare presentation.

Eosinophilic gastroenteritis is a quite uncommon clinical entity usually involving the stomach or small bowel. Occasionally, the colon is involved. We have encountered a case of eosinophilic colitis leading to a left-sided colocolonic intussusception and subsequent large bowel obstruction. This is a unique presentation that, to our knowledge, has not been previously reported. We present our case in detail as well as a review of the literature to better understand this rare clinical entity.

Adult

Study design and baseline characteristics of the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E: SECURE.

Atherosclerotic cardiovascular disease remains a major cause of mortality and morbidity in most developed countries. Experimental and clinical evidence suggests that angiotensin-converting enzyme inhibitors and vitamin E therapy may retard the atherosclerotic process; however, definitive proof in humans is lacking. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) is designed to assess the effects of ramipril--an angiotensin-converting enzyme inhibitor, at 2 doses: 2.5 mg daily (which has little effect on lowering blood pressure) and 10 mg daily--and the antioxidant vitamin E, 400 IU daily, on atherosclerosis progression in 732 patients using a factorial 3 x 2 study design. High-risk patients with a documented history of significant cardiovascular disease or with diabetes and additional risk factors were enrolled and will be followed for 4 years. The extent and progression of atherosclerosis are assessed noninvasively by B-mode carotid ultrasonography. The SECURE trial is a substudy of the larger Heart Outcomes Prevention Evaluation (HOPE) study of 9,541 high-risk patients evaluating the effects of ramipril and vitamin E on major cardiovascular events (cardiovascular death, myocardial infarction, and stroke). The 2 studies are complementary. Whereas HOPE is expected to provide information on major clinical outcomes, SECURE will shed light on the mechanisms by which these effects may be mediated.

Aged

Purification of a rat neurotensin receptor expressed in Escherichia coli.

A truncated rat neurotensin receptor (NTR), expressed in Escherichia coli with the maltose-binding protein fused to its N-terminus and the 13 amino acid Bio tag fused to its C-terminus, was purified to apparent homogeneity in two steps by use of the monomeric avidin system followed by a novel neurotensin column. This purification protocol was developed by engineering a variety of affinity tags on to the C-terminus of NTR. Surprisingly, expression levels varied considerably depending on the C-terminal tag used. Functional expression of NTR was highest (800 receptors/cell) when thioredoxin was placed between the receptor C-terminus and the tag, indicating a stabilizing effect of the thioredoxin moiety. Several affinity chromatography methods were tested for purification. NTR with the in vivo-biotinylated Bio tag was purified with the highest efficiency compared with NTR with the Strep tag or a hexa-histidine tail. Co-expression of biotin ligase improved considerably the in vivo biotinylation of the Bio tag and, therefore, the overall purification yield. Proteolysis of the NTR fusion protein was prevented by removing a protease-sensitive site discovered at the N-terminus of NTR. The ligand binding properties of the purified receptor were similar to those of the membrane-bound protein and the native receptor. The scale-up of this purification scheme, to provide sufficient protein for biophysical studies, is in progress.

Amino Acid Sequence

Associative learning in patients with cerebellar ataxia.

It has been claimed that patients with cerebellar pathology are impaired at associative learning. Patients with cerebellar ataxia (n = 7) were taught a visual-motor associative task. The task was chosen so as to allow comparisons with data currently being collected on the effects of cerebellar lesions on associative learning in monkeys. As a group the patients were as impaired at learning the task as a group of 8 patients with Huntington's disease. When each patient was individually matched with a control of the same age and IQ, some patients with cerebellar ataxia were found to be clearly impaired, but 2 were not. Of the 4 patients who were most clearly impaired, 2 had brainstem pathology and 2 did not. The relevance of these findings is discussed in relation to views concerning the functions of the cerebellum.

Adult

Medicare health maintenance organizations. An industry analysis for the elderly in the USA.

Provides a review and analysis of Medicare health maintenance organizations in the USA. The Porter model of industry structure is used. Discusses the issues of suppliers, buyers, market entry and substitutes. Indicates there is currently no intense rivalry among Medicare risk-based HMOs. However, the Porter model reveals crucial information regarding the forces which drive industry competition. Trends in the field of managed care and Medicare financing continue to be a real challenge regarding future research.

Aged

Evaluation of HER-2/neu (c-erbB-2) oncogene expression in whole organ sections of supraglottic squamous cell carcinoma.

Adequate pathologic material and careful clinical follow-up are prerequisites for the analysis of the expression of particular oncogenic proteins that are prognostically important in squamous cell carcinoma of the larynx. The Gabriel Tucker, Jr, Collection of 150 whole organ specimens allows for the potential immunohistochemical study of the entire tumor. Sections from 32 supraglottic carcinomas were studied immunohistochemically for the presence of HER-2/neu (c-erbB-2) oncogene expression. Long-term follow-up data were available in all cases to assist in determining the prognostic significance of the specified oncogene in supraglottic squamous cell carcinoma. Our study revealed that joint presentation of immune staining for c-erbB-2 and positive lymph node status was significantly associated with distant metastasis (p=.00760).

Adult

The costs of alternative types of routine antenatal care for low-risk women: shared care vs care by general practitioners and community midwives.

OBJECTIVES: To compare the costs to the health service, women and their families of routine antenatal care provided by either traditional obstetrician-led shared care or general practitioner (GP)/community midwife care. METHOD: A multicentre randomized controlled trial in 51 general practices linked to nine maternity hospitals in Scotland: 1667 low-risk pregnant women provided information on costs to the health service. 704 of these women provided information on non-health service costs. RESULTS: GP/midwife antenatal care was found to cost statistically significantly less than shared care. This was the case for investigations carried out at routine antenatal visits (GP/midwife = 87.25 Pounds, shared care = 91.15 Pounds, P = 0.05), staffing costs at routine antenatal visits (GP/midwife = 127.76 Pounds, shared care = 131.09 Pounds, P = 0.001), and non-health service costs incurred by women and their companions (GP/midwife = 118.53 Pounds, shared care = 133.49 Pounds, P = 0.001). While non-routine care in the GP/midwife arm of the trial costs less than in the shared care arm, the difference was not statistically significant (GP/midwife = 83.74 Pounds, shared care = 94.43 Pounds, P = 0.46). The total societal cost of antenatal care was 417.28 Pounds per women in the GP/midwife arm of the trial and 450.19 Pounds in the shared care arm of the trial. This difference was statistically significant (P < 0.001). The application of sensitivity analysis did not change these results. CONCLUSIONS: GP/midwife antenatal care is a satisfactory option for low-risk pregnant women in Scotland provided that clinical outcomes and women's satisfaction are at least the same as those of women with shared care.

Cost Savings