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Biomedical subjects

S Kay

Publications and source records attributed to S Kay.

At least 37 records · Page 2Linked to original sources
PubMed2000

Release from apoptosis correlates with tumor progression in the AKR lymphoma.

Disturbance of apoptosis is an established factor in tumorigenesis. The role of apoptosis in tumor progression is not yet clear. In the present study we compared the tendency to spontaneous apoptosis (and the proliferative capacity) of tumor cells derived from primary (PT) and metastatic tumor (MT) cells of several AKR lymphoma variants. Apoptosis-related gene expression was also compared. Our results indicate that release from apoptosis has a role in the tumor progression of this T cell lymphoma. At the cellular level, a markedly lower apoptotic tendency was observed in MT than in PT cells. The existence of macrophages only in PT also supports the presence of apoptotic cells in local but not in MTs. By contrast, proliferative capacity does not determine tumor aggressiveness in this system. At the molecular level, we found a higher staining intensity for bcl-2 in MT than in PT cells, suggesting that bcl-2 might be responsible for the reduced apoptosis in MT compared to PT cells. Evidence for p53 overexpression was found in the MT cells of one of the variants but in none of the PT. Comparison of Fas receptor, unexpectedly showed an increased expression in MT versus PT cells, possibly indicating resistance to Fas-induced apoptosis in the MT cells.

Animals↗
PubMed2000

Sensitivity to macrophages decreases with tumor progression in the AKR lymphoma.

Resistance to immune reactions, innate or acquired, may be one of the mechanisms responsible for the progression of tumors. We have, indeed shown higher numbers of macrophages surrounding low- as compared to high-malignancy cells. In the present study we examined the level of cell surface molecules known to determine sensitivity to macrophages, namely galactose (GAL) and sialic acid (SA) residues. A histochemical assay for identification of SA by electron microscopy showed a higher cell surface content on metastatic (MT) than on primary (PT) tumor cells. The FACS data seen with fluorescent lectins showed a higher binding of Sambucus nigra agglutinin, which identifies SA attached to terminal GAL in -2.6 or -2.3 linkage, in MT than in PT cells. Binding of Maakia amurensis lectin (MAL-1), which identifies SA at position 3 of GAL, showed that the MT cells contain two subpopulations, one binding more MAL-1 and another less. Cell sorting showed a more aggressive behavior of the first population. The comparison of Peanut agglutinin (PNA) binding, which identifies GAL, demonstrated a decreased amount of PNA receptors in MT as compared to PT cells. Western blot analysis of the membranal proteins with different lectins, identified 3 sialylated glycoproteins. The 88 kDa glycoprotein had no significance for metastatic potential. The 130 kDa glycoprotein was higher in MT than on PT cells. The 220 kDa glycoprotein was practically present only on MT cells. The tendency observed was of a higher level of membranal glycoconjugates terminally sialylated with subterminal galactose residues, inMT cells as compared to PT cells. This may explain the recently found decrease in apoptotic cell death with increasing aggressiveness of the AKR lymphoma and suggests a lower sensitivity to macrophages with tumor progression. Treatment based on the reduction in sialic acid content might render the tumor cells more vulnerable to macrophages. We found, indeed, that Wheat germ agglutinin (WGA) injected in vivo, exerted an inhibitory effect on growth of the lymphoma. We found moreover that WGA-treated tumor cells were more sensitive than nontreated cells to macrophages in vitro.

Animals↗
PubMed2000

Managing people on sip feeds in the community.

Community nurses often have the difficult task of identifying and coordinating the care of under-nourished patients in the community. Studies have shown that patients who are underweight are likely to visit to their general practitioner more often, need more medication and be admitted to hospital. Nutritional sip feeds have been shown to clinically benefit underweight patients suffering from chronic conditions as well as the older people. Adapting ordinary food to meet the patient's nutritional requirements should be considered first, but sip feeds provide an additional source of nutrients when this proves insufficient. All patients on sip feeds should have a clear aim for this nutritional intervention (e.g. the healing of a pressure area) and be monitored regularly.

Community Health Nursing↗
PubMed2000

Apoptosis and cell proliferation capacity in AKR lymphoma malignancy variants.

Dysregulation in apoptotic cell death has recently emerged as a factor in tumorigenesis, but its effect in tumor progression is not yet established. In the present study we evaluated the levels of proliferative and apoptotic cell fractions in a T-cell lymphoma tumor progression model. We compared these features and the expression of apoptosis-related genes in primary tumors of several AKR lymphoma malignancy variants. According to DNA flow cytometry, a considerable proportion of cells (35-40%) was in the proliferative (S + G2/M) phase in all variants, but a slight augmentation with increasing malignancy was noted. Apoptotic cell content was, unexpectedly, the lowest in the less malignant variant. This might be due to the higher content in macrophages observed in this variant, which possibly partly eliminated apoptotic bodies. We found an increase in bcl-2 level with increasing malignancy that was probably counterbalanced by the simultaneous increase observed in the Fas receptor.

Animals↗
PubMed2000

The communicative function of clinical narrative in radiology reporting.

Clinical narrative is often taken as a direct representation of real objects and events such as patients, diseases and treatments. We refer to this conceptualisation as the 'referential function' of clinical narrative. We introduce a complimentary perspective, taking clinical narrative as a construction relative to the situated intentions and routines of communication between author and reader. This perspective, that we call the 'communicative function', highlights the value of some underused features of clinical narrative. In this paper we bring together models of narrative structure and of communication to present a theory of the communicative function of clinical narrative. We pay particular attention to clinical narrative in radiology reporting.

Communication↗
PubMed1999

Revisiting the role of routine retropleural drainage after repair of esophageal atresia with distal tracheoesophageal fistula.

PURPOSE: The aim of this study was to review routine retropleural drainage in esophageal atresia with distal tracheoesophageal fistula (TEF). METHODS: The charts of 52 patients diagnosed with TEF between 1987 and 1997 were reviewed. Data collected included gestational age, birth weight, associated congenital anomalies, respiratory status, operative technique and timing, size of gap, tension on the anastomosis, complications related to the drain, and esophageal anastomotic leak (incidence, diagnosis, and treatment). RESULTS: A total of 52 cases of TEF were identified. Data on sex, gestation age, birth weights, and malformations are summarized. Forty-seven patients underwent a single-stage extrapleural repair. Only one leak was identified in the single-stage group on routine day 7 esophagogram: a Waterson C patient who was clinically well with minimal drainage. The only other leak was in a class C patient who had undergone a staged repair because of an initial long gap. None of the favorable Waterston class patients suffered a leak. CONCLUSIONS: A routine retropleural drain placed near the anastomosis may not be necessary in all cases of TEF. Good prognosis patients (Waterston class A and B) who undergo an uncomplicated extrapleural repair without undue tension do not appear to benefit from having a chest drain in place, and there is potential for complications. In complicated cases, however, retropleural drainage remains a reasonable adjunct.

Anastomosis, Surgical↗
PubMed1999

Prenatal percutaneous needle drainage of cystic sacrococcygeal teratomas.

Prenatal ultrasound (US) permits in utero diagnosis of sacrococcygeal teratoma (SCT), follow-up of tumor size, and the early identification of complications, allowing for a more timely and appropriate delivery. The recommended management of large SCTs is delivery by cesarean section (CS) to prevent dystocia, tumor rupture, hemorrhage, and death. However, even delivery by CS can be difficult, necessitating a large hysterotomy that adds to maternal morbidity. The authors report two cases of cystic SCTs in which prenatal percutaneous drainage allowed for an uncomplicated vaginal delivery. In the first case, a large unilocular cystic SCT was diagnosed at 31 weeks' gestation on prenatal US. The fetal presentation was breech, and the mass was steadily increasing in size, preventing spontaneous version. At 37 5/7 weeks, the cyst was percutaneously drained under US guidance allowing for successful external version. Repeat drainage just before induction of labor permitted a successful vaginal delivery. In the second case, the cystic SCT was percutaneously drained just before induction of labor at full term, again allowing for an uncomplicated vaginal delivery. Prenatal percutaneous needle drainage of cystic SCTs offers an alternative to CS that results in decreased risks for both mother and fetus.

Adult↗
PubMed1999

Apoptotic cell death and related gene expression in metastatic tumors of AKR lymphomas of varying malignancy.

Resistance to apoptosis may be related to tumor progression, due to the implications it might have on both tumor mass and genetic instability. We compared the tendency to spontaneous apoptosis and the proliferative capacity of metastatic growths of several AKR lymphoma variants (TAU-45, TAU-47, TAU-44, TAU-33, TAU-42 and TAU-46, in the order of increasing metastatic potential). We further compared the expression of several apoptosis-related genes. Cell proliferative capacity did not appear to determine malignant behavior since, on the whole, a decrease in S + G2M fraction was observed with increasing malignancy. Sensitivity to apoptotic cell death decreased with increasing malignancy when comparing the TAU-45, TAU-47, TAU-44 and TAU-33 variants, suggesting a role of reduced apoptosis in this T-cell lymphoma. An increase in Bcl-2 content with increasing aggressiveness among these variants, implicates this protein in this tumor progression-related resistance to apoptosis. However, the two variants of highest malignancy, TAU-42 and TAU-46, did not follow the same trend, since they displayed a relatively high content in apoptotic cells and a low Bcl-2 content. Fas receptor expression did not correlate with tendency to apoptosis, indicating that malignant behavior in the AKR lymphoma does not depend on CD95/Fas/APO1 downregulation. Overexpression of p53 was observed only in one of the variants of lowest malignancy.

Journal Article↗
PubMed1999

A patient preference study comparing raltitrexed ('Tomudex') and bolus or infusional 5-fluorouracil regimens in advanced colorectal cancer: influence of side-effects and administration attributes.

Current chemotherapy regimens used in advanced colorectal cancer (ACRC) are similar in terms of efficacy, but differ importantly in terms of side-effects and administration profiles. These differences may impact significantly on patients' lives. We have evaluated patient preferences between raltitrexed ('Tomudex') and 5-fluorouracil-based chemotherapy regimens, with regard to side-effect attributes (raltitrexed and Mayo regimens) and administration attributes (raltitrexed, Mayo, De Gramont and Lokich regimens) in a study based on 82 patients with ACRC. Patients completed a series of rating tasks on how 'upsetting' these attributes were to them using a visual analogue scale (VAS) in a structured interview conducted by a research nurse. Mucositis and asthenia were the most and least upsetting side-effects, respectively. The side-effect profile of raltitrexed was clearly preferred by 78% of patients versus 14% for Mayo (P < 0.001). When side-effects and administration attributes were combined into an overall profile, 91% of patients selected raltitrexed as their clearly preferred regimen, versus 6% for Mayo (P < 0.001). The administration regimen of raltitrexed was ranked most acceptable (mean rank score 1.5 compared with Mayo 2.6, De Gramont 2.7, and Lokich 3.3). Given similar palliative effects, patients with ACRC exhibit preferences for raltitrexed over other regimens, based on administration and/or side-effect attributes. Such preferences should constitute an important part of decisions relating to the choice of chemotherapy regimen in ACRC.

Adult↗
PubMed1999

Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women.

The possibility that the heightened cardiovascular risk associated with the menopause can be reduced by increasing dietary isoflavone intake was tested in 17 women by measuring arterial compliance, an index of the elasticity of large arteries such as the thoracic aorta. Compliance diminishes with age and menopause. An initial 3- to 4-week run-in period and a 5-week placebo period were followed by two 5-week periods of active treatment with 40 mg and then 80 mg isoflavones derived from red clover containing genistein, daidzein, biochanin, and formononetin in 14 and 13 women, respectively, with 3 others serving as placebo controls throughout. Arterial compliance, measured by ultrasound as a pressure (carotid artery) and volume (outflow into aorta) relationship, was determined after each period; plasma lipids were measured twice during each period. Urinary output of isoflavones was also determined. Arterial compliance rose by 23% relative to that during the placebo period with the 80-mg isoflavone dose and slightly less with the 40-mg dose (mean +/- SEM: placebo, .197 +/- .015; 40 mg, .237 +/- 0.007; 80 mg, .244 +/- .014). In the three women receiving continuous placebo, compliance was .16 +/- .022, similar to that during the run-in period for the remaining subjects (.17 +/- .021) [corrected]. ANOVA showed a significant (P = < 0.001) difference between treatments; by Bonferroni multiple comparisons and by paired t test, differences were significant between placebo and 40- and 80-mg isoflavone doses (by paired t test: P = 0.039 for placebo vs. 40 mg; P = 0.018 for placebo vs. 80 mg). Plasma lipids were not significantly affected. An important cardiovascular risk factor, arterial compliance, which diminishes with menopause, was significantly improved with red clover isoflavones. As diminished compliance leads to systolic hypertension and may increase left ventricular work, the findings indicate a potential new therapeutic approach for improved cardiovascular function after menopause.

Adult↗
PubMed1999

Microsurgical reconstruction in abnormalities of children's hands.

Microsurgical reconstruction offers unique opportunities for improving function and appearance in children's hands affected by congenital anomalies or following trauma. Strong parallels exist between the surgery for congenital and post-traumatic defects. This article defines some of the methods used in replacement of skin, the creation of new digits, and the transfer of muscles.

Amputation, Traumatic↗
PubMed1999

Developing shared understanding through simulation.

In this article relevant key findings of a review of selected published work are used to provide a foundation for a new approach to developing a shared understanding of aspects of health care delivery. The new approach makes use of simulation models. It is hoped that this approach will provide support for improved decision-making and for the development of more appropriate enabling tools.

Community Health Services↗
PubMed1999

Constructing scenarios for validating the electronic health care record architecture.

The CEN TC 251 Electronic Health Care Record Architecture is the first part of a four part communication prestandard intended to facilitate the safe communication of clinical information, irrespective of circumstances related to time, distance, and responsibility. The work has important implications for a diversity of stakeholders and must embody clinical principles if it is to succeed. The issue at hand is how to enable clinicians to validate the reference architecture, which is necessarily a technical document, so that they have confidence that it can meet the clinical requirement for safe communication. A model of communication that has been used to ground the architecture is shown to be useful in creating relevant clinical scenarios to permit the first steps towards coherent validation in a systematic way.

Computer Communication Networks↗
PubMed1999

Architecture models to facilitate communication of clinical information.

This is an account of the development and use of a context model for facilitating the communication of clinical information. Its function is to articulate the principle of context within a reference architecture for the Electronic Health Care Record (EHCR). The work required a re-examination of established models of communication, the purpose being to use them to support an architecture that could be reasonably expected to accommodate future, and by definition unforeseeable, developments in EHCR communication. The Context Model is built upon seven recognized constituents of communication. These constituents, although having their origin in the engineering of signal communication, have been found to be useful for explication both in the verbal and textual communication of narratives between people. The electronic health care record architecture supported by the model is the European prestandard ENV13606-1.

Medical Records Systems, Computerized↗
PubMed1998

Coexisting kinetically distinguishable forms of dialkylglycine decarboxylase engendered by alkali metal ions.

The pyridoxal phosphate (PLP) dependent enzyme dialkylglycine decarboxylase (DGD) specifically binds alkali metal ions near the active site. Large ions (Rb+, K+) activate the enzyme while smaller ones (Na+, Li+) inhibit it. Crystallographic results have shown that DGD undergoes a metal ion size dependent structural switch [Hohenester, E., Keller, J. W., and Jansonius, J. N. (1994) Biochemistry 33, 13561], but no evidence for multiple conformations in crystalline DGD was obtained. Here, evidence is presented that DGD-K+ in solution exists in two conformations differing in catalytic competence. Initial rate traces for DGD-K+ exhibit a high degree of curvature due to decreasing activity over time. DGD remains tetrameric under the assay conditions as demonstrated by gel filtration experiments, arguing against the possibility of subunit dissociation as the source of activity loss. Likewise, the mass spectrum of DGD shows a single covalent form. A hysteretic model that assumes two slowly interconverting enzyme forms accounts well for the initial rate data when kinetic parameters from biphasic pre-steady-state kinetics are employed. The fit of the model to the data yields an estimate of 59 +/- 1% for the fast form. A cooperative model cannot account for the data. Double reciprocal plots for coenzyme binding to DGD exhibit two linear phases. Similarly, two kinetic phases are observed in PLP association kinetics. The substitution of Na+ or Rb+ for K+ alters the steady-state kinetic parameters of DGD. Preincubation of DGD-K+ with the competitive inhibitor 1-aminocyclopropane-1-carboxylate (ACC) lowers both kcat and KAIB apparently by drawing the enzyme toward the less active, tighter binding form observed in the pre-steady-state kinetics. These results suggest that the structure of the protein around the alkali metal ion determines the conformational distribution. The transamination reaction with l-alanine was coupled in the pre-steady-state to the LDH-catalyzed oxidation of NADH. This experiment yields an estimate of 68 +/- 4% for the fast form, in agreement with the hysteretic fit to the steady-state data. The reaction of DGD with dithiobis(nitrobenzoate) was used to probe the preexisting forms of DGD. Preincubation of DGD with ACC, like the exchange of Na+ for K+, shifts the conformational distribution, in agreement with the steady-state kinetics. These experiments clearly demonstrate that DGD is a hysteretic enzyme whose conformational distribution is controlled by the identity of the alkali metal ion bound near the active site, and that cooperativity does not play a role in catalysis or regulation.

Alanine↗
PubMed1998

Determinants of the selection of phosphatidylcholine molecular species for secretion into bile in the rat.

Certain phosphatidylcholine (PC) molecular species appear to be secreted into bile preferentially, but the mechanism for this selection remains obscure. We used multivariate analysis to examine the relationship between PC structure and the odds of secretion for individual PC species secreted into bile. PC was isolated from Folch extracts of bile and liver from rats, and individual molecular species of PC were quantified with reverse-phase high-performance liquid chromatography (HPLC). The odds of secretion for a given PC species were quantified as the ratio of its mole% in bile/mole% in liver. Regression analysis indicated that the odds of secretion were significantly related to length of both the sn-1 and sn-2 acyl chains (P < .0001 for both) and to relative hydrophobicity as determined by reverse-phase HPLC (P < .0001). In addition, the relationship between odds of secretion and sn-1 chain length was best described by a parabolic function. Considered together, these characteristics accounted for 88% of the observed differences in odds of secretion. This relationship between PC structure and odds of secretion was strikingly similar to the relationship between PC structure and affinity for bovine PC transfer protein. When multivariate models were used to predict both the odds of secretion and the affinity for PC transfer protein for a set of biologically plausible PC species, there was a linear relationship between the two. The likelihood of a given PC species being secreted into bile can be related to the structural characteristics of the acyl chains without having to postulate the existence of a special pool of PC destined for biliary secretion. Second, the structural characteristics that dictate selection of PC species for secretion into bile are similar to those that determine binding affinity for PC transfer protein, suggesting that the likelihood of a PC being secreted into bile is, in fact, closely related to its binding affinity for PC transfer protein (PC-TP).

Androgen-Binding Protein↗