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Biomedical subjects

K Kelly

Publications and source records attributed to K Kelly.

At least 55 records · Page 3Linked to original sources
PubMed2000

What nursing home residents value in their doctors.

Patient satisfaction is influenced by multiple factors, and different populations are expected to define satisfaction in terms of their novel perspectives. Despite growing interest in patient satisfaction, an extensive literature search reveals no studies of nursing home residents' satisfaction with respect to medical care. In an initial qualitative study using transcripts of interviews conducted as part of a state quality control mandate, categories are identified that make up this population's construct of satisfaction and dissatisfaction. These categories serve as building blocks for designing future studies investigating these issues and allowing for comparison of nursing home residents' ideas of satisfaction and dissatisfaction to other older patients, including those in an outpatient geriatric setting.

Aged↗
PubMed2000

Glutamic acid decarboxylase autoantibodies in controlled and uncontrolled epilepsy: a pilot study.

There have been anecdotal reports of raised glutamic acid decarboxylase (GAD) autoantibodies in patients with refractory epilepsy. We measured serum GAD autoantibodies in 105 patients with idiopathic or symptomatic epilepsy. There was no significant difference in the absolute titre of GAD autoantibody between patients with controlled and uncontrolled epilepsy. However, four female patients with uncontrolled epilepsy had levels that were over three times above the highest detected in the seizure-free group, three of whom also tested positive for pancreatic islet cell antibodies. Larger scale studies, perhaps comparing different epilepsy syndromes, are required to determine the exact clinical role of GAD autoantibodies in epilepsy.

Adolescent↗
PubMed2000

Docking of sulfonamides to carbonic anhydrase II and IV.

Starting with a known active site of a protein and a database of compounds, one would like to quickly identify a few compounds that "dock" into the active site and obtain "good" binding free energies. The main goal of current automated docking procedures is to predict the "best" substrate-enzyme complex while other programs such as UHBD and DelPhi can be used to compute binding free energies. In this paper, we will focus on the application of docking methods and parameters to study substrate-enzyme interactions of a metalloenzyme system. Specifically, we report on the docking of sulfonamides to carbonic anhydrase II and IV, which are of interest due to their application in glaucoma therapy. Using a standard docking protocol, it is possible to correctly predict not only the orientation of inhibitors to a specific isozyme, but also determine the qualitative affinity for a group of inhibitor for an isozyme.

Algorithms↗
PubMed2000

A cortisol surge mediates the enhanced expression of pig intestinal pyrroline-5-carboxylate synthase during weaning.

Citrulline synthesis from glutamine is enhanced remarkably in enterocytes of weanling pigs, but the molecular mechanism(s) involved are not known. The objective of this study was to determine whether a cortisol surge mediates the enhanced expression of intestinal citrulline-synthetic enzymes during weaning. Jejunal enterocytes were prepared from 29-d-old weanling pigs treated with or without metyrapone (an inhibitor of cortisol synthesis), or from age-matched unweaned pigs. The mRNA levels and activities of phosphate-dependent glutaminase (PDG), pyrroline-5-carboxylate synthase (P5CS), ornithine aminotransferase (OAT), carbamoyl-phosphate synthase I (CPS-I) and ornithine carbamoyltransferase (OCT) were determined. The mRNA levels for PDG, P5CS, OAT and OCT were 139, 157, 102 and 55% higher, respectively, in weanling pigs compared with suckling pigs. The activities of PDG and P5CS were 38 and 692% higher, respectively, in weanling pigs compared with unweaned pigs, but the activities of OAT, CPS-I and OCT did not differ between these two groups of pigs. The effects of metyrapone administration to weanling pigs were as follows: 1) prevention of a cortisol surge, 2) abolition of the increases in both mRNA levels and activity of P5CS, 3) no alteration in the mRNA levels and activities of PDG and CPS-I, 4) increases in the mRNA levels for OAT (216%) and OCT (39%) and in OAT activity (30%), and 5) prevention of the increase in intestinal synthesis of citrulline from glutamine. These results suggest that increased P5CS activity reflects in large part the increased levels of P5CS mRNA and is responsible for the increased synthesis of citrulline from glutamine in enterocytes of weanling pigs; these increases may be mediated by a cortisol surge during weaning that can be blocked by metyrapone administration.

Animals↗
PubMed2000

Adjuvant and neoadjuvant chemotherapy for non-small cell lung cancer: a time for reassessment?

Surgical resection has limited success in curing non-small cell lung cancer (NSCLC), particularly among patients with locally advanced disease (stage IIIA). Combined modality regimens, utilizing surgery, radiotherapy, and chemotherapy, have improved response rates, although they have not been shown to significantly impact survival among patients with completely resected stage I and II NSCLC. Future improvements in NSCLC therapy, currently under investigation, are likely to come from newer agents shown to be active in this disease and from alternative schedules, such as neoadjuvant or concurrent combined modality treatments. Neoadjuvant cisplatin-based chemotherapy has already been shown to increase cure rates in stage IIIA NSCLC, from 10 to 15% to 25 to 30%. Newer active agents, such as paclitaxel, vinorelbine, and gemcitabine, may be able to advance the cure rate even further. Radiotherapy, which has been shown to decrease the rate of local recurrence, may play a role as well.

Antineoplastic Agents↗
PubMed2000

New combinations in the treatment of lung cancer: a time for optimism.

Strides have been made in the treatment of lung cancer in the last decade that warrant a more optimistic outlook toward the disease. The recent development of several new agents with single-agent activity, including paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan, is important, and those agents offer even greater potential when they are used in combination chemotherapy regimens or in combined-modality programs. The experience to date with therapy results with these agents in the treatment of lung cancer is reviewed and is compared to results documented with the current standard treatments for lung cancer, namely, cisplatin and cisplatin-based combination regimens. Published and ongoing trials are outlined, and directions for future research and the future goals of lung cancer therapy are outlined. The availability of newer chemotherapeutic agents that are active in lung cancer has led to response rates as high as 40% in the treatment of non-small cell lung cancer. These drugs have been shown to be active in combination drug regimens as well as when combined with radiotherapy. Future research will focus on using these agents in two- and three-drug regimens as radiation sensitizers and in combination programs with new drugs and biological agents with apparent activity against this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

New chemotherapy agents for small cell lung cancer.

BACKGROUND: Approximately 45,000 new cases of small cell lung cancer (SCLC) will be diagnosed in the United States this year. Combination chemotherapy is the cornerstone of treatment for all stages of this disease and results in high response rates (65 to 85%), leading to a meaningful survival advantage for these patients. Patients with limited-stage disease enjoy a median survival of 10 to 15 months with chemotherapy, as compared to 3 months without drug therapy. With addition of chest radiotherapy, survival is further prolonged to 12 to 20 months. Patients with extensive-stage disease experience an average survival of 1.5 months without chemotherapy and 7 to 11 months with chemotherapy. However, no further improvement in survival has been demonstrated since combination chemotherapy regimens were introduced in the late 1970s and early 1980s, despite evaluating numerous strategies; the 5-year survival for all patients remains dismal at 5%. Clearly, new chemotherapy agents with novel mechanisms of action are needed. FOCUS: This article will review the experience to date with six new agents that are active against SCLC. It includes two taxanes (paclitaxel and docetaxel), vinorelbine, two camptothecin derivatives (topotecan and irinotecan), and gemcitabine. Single-agent activity as well as combination regimens with other agents and radiotherapy will be discussed. The role of maintenance therapy with oral matrix metalloproteinase inhibitors also is evaluated.

Antineoplastic Agents↗
PubMed2000

Combinations of three chemotherapeutic agents and two chemotherapeutic agents plus a targeted biologic agent in the treatment of advanced non small-cell lung cancer.

Lung cancer is the most common cause of cancer death in the world. In the United States, more than 28% of all cancer deaths are from lung cancer. In the past decade, a number of new drugs were introduced into the treatment of lung cancer including taxanes, gemcitabine, vinorelbine, and irinotecan. Combinations of one of these drugs with cisplatin, with carboplatin, or with one another were shown to be superior to best supportive care, to single-agent cisplatin, and in some instances, to a podophyllotoxin and cisplatin. Comparisons of the various two-drug combinations showed that they are equivalent in efficacy although there are differences in convenience, cost, and toxicity. Many of these two-drug combinations are less toxic than older combinations, which allowed for the development of three-drug combinations that could be given in full dose and with acceptable toxicity. Phase II trials of several three-drug combinations including carboplatin/paclitaxel/gemcitabine and cisplatin/vinorelbine/gemcitabine showed response rates and survival rates that were somewhat higher than anticipated with a two-drug combination. These data led to three randomized trials of a doublet combination versus a triplet combination. Each of these trials showed a higher response rate and higher toxicity rates with the triplet combination. The toxicity rates were still acceptable with the triplet combinations. The survival was also superior in the triplet arms of each of the randomized trials. Unfortunately, the sample size in each of these studies was small and the survival differences are not statistically significant. Therefore, additional larger randomized trials are sorely needed. During the past decade, new molecularly targeted agents were introduced into the treatment of lung cancer and completed phase I and II trials. Objective responses were noted with many of these new agents. Several combinations of doublet chemotherapy with a new targeted agent have completed phase II trials with encouraging results. Some of these new triplets are now in phase III randomized trials.

Journal Article↗
PubMed2000

Determination of the tissue sites responsible for the catabolism of large high density lipoprotein in the African green monkey.

In vivo multicompartmental modeling of the turnover of HDL subfractions has suggested that HDL containing four molecules of apoA-I per particle and no other apolipoproteins (large LpA-I) are terminal particles in plasma. We hypothesized that these terminal particles were the end product of HDL metabolism and, as such, would be cleared preferentially by the liver. Thus, the purpose of this study was to determine: 1) the tissue sites of catabolism of large LpA-I in African green monkeys, and 2) whether saturated versus n;-6 polyunsaturated dietary fat affected tissue accumulation. Large LpA-I were isolated, without ultracentrifugation, by size exclusion and immunoaffinity chromatography and radiolabeled with either the residualizing compound, (125)I-labeled tyramine cellobiose (TC), or with (131)I. After injection into recipient animals, the plasma die-away of the radiolabels was followed for 12 or 24 h, after which the animals were killed and tissues were collected for determining radiolabel sites of catabolism. The plasma die-away of the (125)I-labeled TC-LpA-I and (131)I-labeled LpA-I doses was similar suggesting that the TC radiolabeling did not modify the metabolism of the large LpA-I dose. The liver, adrenal, kidney, and spleen had the greatest accumulation of large LpA-I degradation products on a per gram tissue basis. On a whole organ basis, the liver was the major site of large LpA-I degradation in both the 12-h (15.4 +/- 0.3% of injected dose) and 24-h (9.1 +/- 0.6% of injected dose) catabolic studies. The kidney, compared to the liver, had less uptake of large LpA-I radioactivity in either study (1.3 +/- 0.4% and 1.2 +/- 0.3% of injected dose). There was no apparent influence of dietary fat type on the tissue accumulation of large LpA-I. We conclude that the liver is the primary site of catabolism of large LpA-I in the African green monkey.

Animals↗
PubMed2000

Cost savings associated with changes in routine laboratory tests ordered for victims of trauma.

Not all trauma victims evaluated by the trauma service require a full complement of laboratory tests upon admission. This study set out to determine the cost savings and safety of limited laboratory testing of trauma victims. Before 1998, our admission trauma protocol included 11 laboratory tests for all trauma victims. In 1998, we created two categories: Trauma Blue--severe injury likely (Glasgow Coma Score <13; systolic blood pressure <100 mm Hg at any time; significant head, chest, abdominal, or proximal long bone injury; or clinical suspicion of need for operative or intensive care unit management) and Trauma Yellow--severe injury unlikely. The triage decision was made by the team leader or attending physician. Trauma Blue laboratory tests included an arterial blood gas, blood alcohol, type and screen or crossmatch, and urine dipstick. All patients who did not meet Trauma Blue criteria were entered in the Trauma Yellow group. There were only two tests for the Trauma Yellow group, a venous blood gas and blood alcohol. All arterial and venous blood gases measured pH, pO2, pCO2, HCO3, base deficit, hemoglobin, sodium, potassium, and ionized calcium. Other laboratory tests were done if requested by the trauma team leader or attending physician. All trauma admissions for a 3-month period were entered into this prospective study. The admitting trauma surgeon was surveyed after each admission to evaluate any problems in patient care. The test group was compared with a historical control of 100 consecutive patients under the original laboratory trauma protocol. One hundred and forty-eight (148) patients were entered into the study. Average laboratory cost per patient was $29.82 less with the study protocol. No patient care problem was identified. A cost savings of $29.82 per patient or $20,000.00 a year was realized for our institution, with no change in the quality of patient care. Trauma protocols designed to reflect a patient's potential for serious injury can result in a significant cost savings while preserving patient safety.

Clinical Protocols↗
PubMed2000

Respiratory symptoms and use of medical care associated with child day care and health care plan among preschool children.

This study compared the risk of respiratory infections in pre-school children (under 6-year-old) attending day care center and those taken care of at home by controlling for the type of health plan and sociodemographic characteristics. The study population consists of members of two health plans residing in two South Carolina counties. Results show that the risks of respiratory symptoms were higher among children attending day care settings than those taken care of at homes although this relationship is more apparent among Medicaid children than among HMO children. While the type of child care has weak influence on medical care utilization, the type of health plan exerts strong influence on utilization for both day care and home care groups.

Chi-Square Distribution↗
PubMed2000

A phase I/II trial of paclitaxel, carboplatin, and gemcitabine in untreated patients with advanced non-small cell lung cancer.

Paclitaxel and carboplatin is widely used in the treatment of patients with advanced non-small cell lung cancer (NSCLC); however, median survival remains < 1 year. One strategy to improve survival is to add a third active drug with a differing mechanism of action. Gemcitabine is a novel antimetabolite with considerable activity in NSCLC. The primary objective of this Phase I/II study was to determine the maximally tolerated dose of gemcitabine administered with fixed doses of paclitaxel and carboplatin in untreated patients with advanced NSCLC.

Adenocarcinoma↗
PubMed1999

Haemochromatosis mutations in North-East Scotland.

The HFE gene and its mutations C282Y and H63D cause hereditary haemochromatosis (HH). Among 54 affected individuals from North-East Scotland, 91% were homozygous for C282Y and 5.5% were compound heterozygotes for C282Y and H63D. The general population allele frequencies were high (8% and 15.7% for C282Y and H63D respectively). Although it is likely that HH is under diagnosed, these figures suggest that disease expression is variable, and many of those with the genetic predisposition HH will never develop the clinical consequences of iron overload. This has implications for diagnosis and predictive testing.

Female↗
PubMed1999

Structural characterization of mouse CD97 and study of its specific interaction with the murine decay-accelerating factor (DAF, CD55).

CD97 is a newly identified, activation-associated human leucocyte antigen with seven putative transmembrane domains. It has an extended extracellular segment containing several adhesion molecule structure motifs, and has been shown to interact with the human complement regulator, decay-accelerating factor (DAF, CD55). To understand further the interaction between CD97 and DAF, as well as the structure and function of CD97 in general, we have cloned the mouse CD97 cDNA and studied the encoded protein for its membrane association property and ability to interact specifically with the murine decay-accelerating factor. The full-length mouse CD97 cDNA that we have cloned and characterized encodes a protein that is 60% identical to the three epidermal growth factor (EGF) domain-containing form of human CD97 but does not contain the Arg-Gly-Asp (RGD) motif which is present in human CD97. Two other alternatively spliced forms of mouse CD97 were also identified. These forms differ by the number of EGF-like sequence repeats present in the N-terminal region. Northern blot analysis revealed that CD97 is expressed widely in mouse tissues and in resting as well as activated cultured mouse splenocytes. Transient transfection of human embryonic kidney (HEK) 293 cells with the mouse CD97 cDNA in a green-fluorescence protein vector (pEGFP-N1) showed plasma membrane targeting of the expressed protein. Western blot analysis confirmed its membrane association and identified the existence of a processed C-terminal fragment, supporting the notion that CD97 on the cell membrane is composed of post-translationally generated subunits. Adhesion studies demonstrated that normal, but not DAF knockout mouse erythrocytes and splenocytes adhered to mouse CD97-transfected HEK cells. The interaction of CD97 and DAF was found to be species-restrictive in that human erythrocytes were unable to bind to mouse CD97-transfected HEK cells. These results indicate that the general structure, membrane association property and DAF-binding ability of CD97 are conserved and that the adhesive interaction between CD97 and DAF is independent of the RGD motif. The finding that CD97 is distributed widely among various mouse tissues suggests that CD97 may have other roles beyond lymphocyte activation.

Amino Acid Sequence↗