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Biomedical subjects

B Jennings

Publications and source records attributed to B Jennings.

At least 19 recordsLinked to original sources

From the urban to the civic: the moral possibilities of the city.

Relating bioethics to the philosophy of the city creates the possibility for developing the field along paths not yet explored. In the Western tradition, the city has been understood as the venue for two quite different forms of activity and two different types of moral possibility. In one guise, the city is an urbs, a center of commerce, market exchange, and social individualism. In another guise, the city is a civitas or polis, the space of active democratic citizenship, equality under law, and civic virtue. As civitas, classical philosophers regarded the city as the place of moral growth and full human self-realization. These two possibilities of human moral and political experience in the city have given rise to distinct traditions of political theory--liberalism and civic republican and democratic theory. This article traces these conceptual configurations into the domain of contemporary bioethics, arguing that most work in the field has drawn on the liberal tradition and hence has been insufficiently critical of the moral paradigm of market individualism and unduly inattentive to the values of civitas and the civic tradition. It argues for the creation of a form of civic bioethics and explores some of the theoretical foundations that type of bioethics would require.

Bioethics↗

A novel germ line juxtamembrane Met mutation in human gastric cancer.

Activating mutations in the Met receptor tyrosine kinase, both germline and somatic, have been identified in human papillary renal cancer. Here we report a novel germline missense Met mutation, P1009S, in a patient with primary gastric cancer. The dosage of the mutant Met DNA was elevated in the tumor when compared to its matched normal DNA. Therefore, as with hereditary renal papillary cancer, the mutant Met allele may also be selectively duplicated in the tumor. Different from previously reported Met mutations, which occur in the tyrosine kinase domain, this missense mutation is located at the juxtamembrane domain, and is not constitutively activated. However, following treatment with HGF/SF, the P1009S mutant Met protein, expressed in NIH3T3 cells, displays increased and persistent tyrosine phosphorylation compared to the wild-type Met. Importantly, these cells also form colonies in soft agar, and are highly tumorigenic in athymic nude mice. A second nucleotide change in this region of Met, T1010I, was found in a breast cancer biopsy and a large cell lung cancer cell line. Although this previously reported 'polymorphism' did not stimulate NIH3T3 cell growth in soft agar, it was more active than the wild-type Met in the athymic nude mice tumorigenesis assay, suggesting that it may have effects on tumorigenesis. Met has been shown to be highly expressed in human gastric carcinoma cell lines, and our results raise the possibility that activating missense Met mutations could contribute to tumorigenesis of gastric cancer.

3T3 Cells↗

Predictors of 30-day hospital readmission after coronary artery bypass.

BACKGROUND: Risk factors for 30-day hospital readmission following coronary artery bypass grafting (CABG) have not been established. METHODS: We prospectively followed 485 consecutive patients who underwent isolated primary CABG at our institution in 1997. Patients were contacted by telephone at 30 days following operation to determine readmission status. RESULTS: The overall readmission rate was 16% (76 of 485). Female gender (25% versus 11%, p = 0.001) and diabetes (22% versus 12%, p = 0.005) were associated with significantly higher readmission rates. The relationship between female gender and readmission persisted after correcting for age and other comorbidities. Congestive heart failure trended towards a significant relationship with increased readmission rate (22% versus 14%, p = 0.09). There were no significant associations between 30-day readmission rate and age, hypertension, chronic obstructive pulmonary disease, history of myocardial infarction, peripheral vascular disease, creatinine level of > or = 1.4 mg/dL, or decreased left ventricular ejection fraction (< 40%). CONCLUSIONS: These data show that most of the classic risk factors for postoperative mortality are not necessarily associated with increased readmission. However, female gender and diabetes are associated with greater than twice the risk of 30-day readmission following CABG.

Aged↗

Screening for diabetic retinopathy using computer based image analysis and statistical classification.

Diabetic retinopathy is one of the most common causes of blindness in Europe. However, efficient therapies do exist. An accurate and early diagnosis and correct application of treatment can prevent blindness in more than 50% of all cases. Digital imaging is becoming available as a means of screening for diabetic retinopathy. As well as providing a high quality permanent record of the retinal appearance, which can be used for monitoring of progression or response to treatment, and which can be reviewed by an ophthalmologist, digital images have the potential to be processed by automatic analysis systems. We have described the preliminary development of a tool to provide automatic analysis of digital images taken as part of routine monitoring of diabetic retinopathy in our clinic. Various statistical classifiers, a Bayesian, a Mahalanobis, and a KNN classifier were tested. The system was tested on 134 retinal images. The Mahalanobis classifier had the best results: microaneurysms, haemorrhages, exudates, and cotton wool spots were detected with a sensitivity of 69, 83, 99, and 80%, respectively.

Biometry↗

Collaboration in disability policies--collaboration between stakeholders of disability policies in the South and in the North.

Four studies have been recently undertaken at the Centre for International Child Health on the collaboration between the stakeholders of disability policies, in Southern and Northern countries. Informed by the literature, the authors have explored the roles disabled people's organizations, non-governmental organizations, government and professionals play in the design, provision and evaluation of services for disabled people. They also highlight the different forms participation can take and their most relevant features. The main factors influencing collaboration processes are then classified in three different categories: social factors, ideology-related factors and project-related factors. They are subsequently analysed. The first group encompasses the societal framework in which collaboration may take place, while the identity of the stakeholders is reflected in the ideology-related factors. The nature of the activities undertaken by stakeholders is characterized by the third group of factors. In the conclusion it is suggested that stakeholders, and especially disabled people's counterparts, should increase their awareness of the social model of disability, adopt participatory practices and promote participation at higher levels. However, they should acknowledge that it implies more trust between partners and an alteration of their structures.

Community Networks↗

Hospital readmission after cardiac surgery. Does "fast track" cardiac surgery result in cost saving or cost shifting?

BACKGROUND: Intense medical and economic pressures have created "fast track" cardiac surgery in which clinical services are streamlined and early discharge is encouraged. Does this strategy promote significant cost saving or merely cost shifting? In a global system of reimbursement, the economic benefit of decreasing patient length of stay may be offset by high rates of patient readmission. This study was undertaken to determine the 30-day readmission rate after cardiac surgery and to analyze trends of readmission diagnoses. METHODS AND RESULTS: From October 1, 1996 to July 31, 1997, 460 consecutive cardiac surgical operations were performed at 1 institution. There were 25 deaths and 8 patients who remained as inpatients at the 30-day postoperative deadline for readmission. Two patients had 2 operations. Therefore, 527 operations were performed on 525 patients. There were 110 readmissions after 527 operations for a readmission rate of 20.9%. A significant number of readmissions (49%) were to outside hospitals. Readmission diagnoses were: atrial fibrillation (23%); angina, congestive heart failure, or ventricular tachycardia (20%); leg wound (15%); sternal wound (5%); pneumonia (5%); gastrointestinal complaints (5%); neurologic event (2%); and miscellaneous (25%). Patients discharged > or = 7 days postoperatively were twice as likely to be readmitted as those discharged on postoperative days 4, 5, or 6. CONCLUSIONS: Readmission after cardiac surgery is common and frequently (49%) to outside institutions. Patients discharged > or = 7 days postoperatively represent the patients at greatest risk of readmission and, therefore, warrant closer scrutiny before discharge.

Adult↗

Beyond retinal screening: digital imaging in the assessment and follow-up of patients with diabetic retinopathy.

Many screening methods are available for detecting diabetic retinopathy. However, once patients develop retinopathy, it is unclear as to what method should be used for their review. We describe a novel and integrated system for the screening and treatment of diabetic retinopathy using high street optometrists for primary screening and digital imaging as a secondary screening tool, with referral to a joint retinal clinic only where ophthalmological intervention may be required. Of 3586 patients screened by optometrists, 328 were classified as having moderate/severe pre-proliferative retinopathy or diabetic maculopathy. Patients with proliferative retinopathy (1% of the total) were recalled directly to the joint retinal clinic. A consecutive sample (281) of these patients, together with a further 100 classified by the optometrists as having no or background retinopathy were compared using digital images and standard 35 mm colour transparencies. These, together with the original optometrist reports, were reviewed independently and individually by an ophthalmologist. A further sample of 124 patients who had undergone both digital imaging and ophthalmologist slit-lamp examination were also compared. Comparison of 35 mm colour transparencies with optometrist reports showed the latter had a sensitivity for detecting sight-threatening retinopathy (STR) of 62%, a specificity of 84%, and a kappa score of 0.62. The results for digital images were 90%, 97%, and 0.90, respectively, although the extent of retinopathy was under-reported in 10 patients. With ophthalmologist slit-lamp examination as the gold standard, the sensitivity of digital imaging was 90% with a substantial level of agreement between them (kappa 0.61). We conclude that digital images provide an efficient method for the follow-up of patients with established or previously treated retinopathy.

Adult↗

Comparison of 3 different doses of budesonide and placebo on the early asthmatic response to inhaled allergen.

BACKGROUND: A simple laboratory method to evaluate relative potency of inhaled corticosteroids in asthma would be valuable. Single-dose studies with the allergen-induced late asthmatic response have failed to show a useful dose-response relationship. Treatment for several days with inhaled corticosteroids will also inhibit the allergen-induced early asthmatic response. METHODS: Twelve atopic asthmatic subjects were studied during a season when no medications were required except ipratropium bromide as needed. These subjects had positive allergen and methacholine inhalation tests and FEV1 greater than 70% of predicted value. A double-blind, randomized, cross-over study compared placebo and budesonide 100, 200, and 400 microg administered by means of Turbuhaler twice daily for 7 days with 6-day washout periods. Methacholine PC20 was measured before and after 6 days of treatment, and allergen PC15 was measured after 7 days of treatment. RESULTS: The allergen PC15 (n = 11) was significantly larger (P = .0001) for all doses of budesonide compared with placebo, but there was no significant difference between the 3 doses of budesonide, and no dose response was demonstrated. The methacholine PC20 was significantly larger after all budesonide treatments compared with placebo (P = .024), but there was no difference between the 3 doses. There was a progressive increase in the allergen PC15 chronologically (sequence effect) that was not explained by improvement in FEV1 or airway responsiveness; sequence effects were not seen for FEV1 or for pretreatment or posttreatment methacholine PC20. Statistical adjustment for sequence effect did not alter allergen PC15 statistics. CONCLUSION: A 7-day course of budesonide administered by means of Turbuhaler at 200, 400, or 800 microg per day provided marked and significant inhibition of the allergen-induced early asthmatic response compared with placebo. There was, however, no difference between the 3 doses. Therefore this method with these doses is not useful for providing assessment of relative potency.

Administration, Inhalation↗

Genetic analysis of the phi X174 DNA binding protein.

The phi X174 J protein is 37 amino acids in length and contains 12 basic residues. There are no acidic amino acids in the protein. The basic residues are concentrated in two clusters in the N-terminus which are separated by a proline-rich region. To investigate the morphogenetic functions of the J protein and possible mechanisms by which it may bind DNA, a genetic analysis was conducted. Lysine --> leucine and arginine --> leucine substitutions were generated within the basic amino acid clusters. At least three substitutions were required to eliminate viability in vivo. Lethal mutants with three or four substitutions exhibit dominant lethal phenotypes, indicating that the mutant proteins retain enough function to interfere with productive assembly. In cells infected with a dominant lethal mutant, noninfectious packaged particles were produced. Infectivity can be restored by second-site suppressors in the viral coat protein which disrupt polar interactions atop the threefold axis of symmetry in the capsid. The viability of strains containing compensating frameshift mutations within the proline-rich region suggests that only the proline residues in this segment are critical for efficient function.

Amino Acid Sequence↗

Comparison of the antiasthmatic, oropharyngeal, and systemic glucocorticoid effects of budesonide administered through a pressurized aerosol plus spacer or the Turbuhaler dry powder inhaler.

To determine therapeutically and systemically equivalent dosages of budesonide inhaled through the Turbuhaler dry powder inhalation device (Astra Pharma Production AB, Södertälje, Sweden) or pressurized metered-dose inhaler (pMDI) plus Nebuhaler spacer (Astra Pharma Production AB), we compared these devices in a randomized, open, parallel-group trial. Adults with moderate to severe asthma inhaled budesonide (0.4, 0.8, 1.6, and 2.4 mg/day), for 2 weeks at each dose level, through the Turbuhaler (n = 30) or pMDI + Nebuhaler (n = 28). Dose-dependent effects were demonstrated on asthma symptoms (p = 0.0001), daily peak expiratory flow (p = 0.02), blood eosinophils (p = 0.0001), urinary cortisol output per day (p = 0.0001), serum cortisol (p = 0.006), serum osteocalcin (p = 0.0001), and the oropharyngeal Candida colony count (p = 0.0007. analysis of covariance). The ratio of the responses to the two inhalation devices approximated 1.0 for each index measured; that is, no significant between-device difference was found (p > or = 0.29). However, the 95% confidence limits for the ratio of their respective systemic effects on osteocalcin production were 0.83 to 1.48. Thus in adults who use inhalation devices efficiently and have optimally controlled asthma, conversions from the pMDI + Nebuhaler to the Turbuhaler may reasonably be made at milligram equivalent doses of budesonide, then down-titrated to minimize possible systemic effects. Because earlier studies have shown that the Turbuhaler can double intrapulmonary drug delivery in comparison with a pMDI without a spacer, a 50% dose reduction may be indicated when converting from a pMDI to the Turbuhaler.

Administration, Inhalation↗

Evaluation of single-dose inhaled corticosteroid activity with an allergen challenge model.

BACKGROUND: Inhaled corticosteroids are the most commonly used antiinflammatory agents for asthma. There is no simple way to compare objectively the relative potency of inhaled corticosteroids. The allergen-induced late asthmatic response (LAR) can be suppressed by a single dose of inhaled corticosteroid. OBJECTIVE: This study was undertaken to evaluate LAR as a model for the determination of the relative potency of single doses of inhaled corticosteroids. METHODS: We compared doses of 200 and 800 microg of a highly active inhaled corticosteroid (budesonide) with placebo and a marginally active investigational inhaled corticosteroid (D5159). Ten atopic patients with asthma completed a randomized, double-blind, double-dummy, multicenter, four-way, crossover trial. A standardized allergen challenge with the identical dose of allergen was performed 10 minutes after each of four blinded, single-dose treatments: 200 microg of budesonide, 800 microg of budesonide, 8 mg of D5159, and placebo, all administered from Turbuhaler. The LAR was recorded as the maximum percent fall in FEV1 between 4 and 7 hours, and the allergen-induced increase in methacholine airway responsiveness at 24 hours was recorded as the A log PC20 from the day before to the day after allergen challenge. RESULTS: There were no significant differences in the early asthmatic responses during the 4 days; the mean maximum percent in FEV1 fall ranged between 19.5% and 22%. D5159 produced a slight inhibition of the LAR with maximum percent fall in FEV1 recorded as 28.8% +/- 5.0% for D5159 versus 34.1% +/- 4.8% for placebo (p < 0.05). There was a greater reduction recorded after administration of the two doses of budesonide. The mean LAR was 15.1% +/- 3.8% for 200 microg of budesonide and 11.2% +/- 2.3% for 800 microg of budesonide (p < 0.01 compared with placebo and D5159). The two doses of budesonide were not statistically different. Airway responsiveness to methacholine increased by 1.07 doubling doses 24 hours after allergen challenge. This increased airway responsiveness was slightly, but not significantly, reduced by the three active treatments (0.6 to 0.91 doubling doses). CONCLUSION: The allergen-induced LAR model was able to differentiate a single dose of an active inhaled corticosteroid from placebo and a highly potent inhaled corticosteroid from a weak inhaled corticosteroid. The model did not differentiate between 2 fourfold doses of the highly active inhaled corticosteroid (at the doses used in this study), neither for the fall in FEV1 nor for the increase in airway hyperresponsiveness.

Administration, Inhalation↗

Individual rights and the human good in hospice.

Hospice care today faces economic, cultural, and social challenges that will force it to rethink its basic ethical mission and its basic values if it is to grow and prosper. Three different values can be said to inspire the hospice movement: palliation and the relief of suffering, enhancing individual control and autonomy at the end of life, and the value of healing or maintaining meaning and personal integrity in the dying process. An emphasis on palliation alone will not be sufficient to sustain a comprehensive hospice benefit in the future. An emphasis on patient autonomy alone is not in keeping with the history or spirit of the hospice movement, which in fact has had a vision of "good" dying. The notion of healing or making whole provides the richest and most adequate concept upon which to ground the social and ethical case for hospice care in the future.

Ethics, Professional↗

Directive counseling on long-acting contraception.

National rates of unintended births are a major public health concern. The availability of highly effective long-acting contraceptives has prompted some public officials to promote the coercive use of these methods to reduce such problems as intergenerational poverty and child abuse. Broad-brush public policies that require long-term contraceptive use are unethical. However, persuasion to use these methods can be appropriate. One place for exerting ethically justified influence is in family planning counseling. The dominant nondirective counseling model, which excludes the possibility of vigorous persuasion, is overly rigid. Family planning professionals should develop practice protocols that permit and guide the exercise of directive counseling to use long-acting contraception.

Child↗