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Biomedical subjects

C O'Brien

Publications and source records attributed to C O'Brien.

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

Consistency in the observation of features used to classify duct carcinoma in situ (DCIS) of the breast.

AIM: To determine interobserver and intra-observer agreement in the assessment of cytological grade and intraduct necrosis in pure duct carcinoma in situ (DCIS) of the breast. METHODS: Sixty unselected cases with illustrated diagnostic criteria were circulated to 19 practising histopathologists. RESULTS: Overall agreement was moderate for cytological grade in three categories: 71% agreement; weighted kappa (kappa w), 0.36; intraduct necrosis in three categories (absent, present, extensive): 76% agreement; kappa w, 0.57; and the Van Nuys classification system: 73% agreement; kappa w, 0.48. Agreement was no better among observers participating in the National External Quality Assurance Programme. Intra-observer agreement for cytological assessment (69.6% agreement; kappa w, 0.52) and intraduct necrosis (68.3% agreement; kappa w, 0.48) was moderate, suggesting that individual variation rather than precision of criteria contributes to the lack of agreement. CONCLUSIONS: Moderate agreement on observations can be achieved by non-specialist pathologists, with better agreement on necrosis than cytological grade. There was evidence of consistent individual bias towards over or under scoring cytological grade, which could be corrected with adequate and prompt feedback.

Breast Neoplasms↗
PubMed2000

Physiological and radiological characterisation of patients diagnosed with chronic obstructive pulmonary disease in primary care.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common although often poorly characterised, particularly in primary care. However, application of guidelines to the management of such patients needs a clear understanding of the phenotype. In particular, the British guidelines for the management of COPD recommend that the diagnosis is based on appropriate symptoms and evidence of airflow obstruction as determined by a forced expiratory volume in one second (FEV(1)) of <80% of the predicted value and an FEV(1)/VC ratio of <70%. METHODS: A study was undertaken of 110 patients aged 40-80 years who had presented to their general practitioner with an acute exacerbation of COPD. The episode was treated at home and, when patients had recovered to the stable state (two months later), they were characterised by full lung function tests and a high resolution computed tomographic (HRCT) scan of the chest. RESULTS: There was a wide range of impairment of FEV(1) which was in the normal range (>/=80%) in 30%, mildly impaired (60-79%) in 18%, moderately impaired (40-59%) in 33%, and severely impaired (<40%) in 19% of patients. A reduced FEV(1)/VC ratio was present in all patients with an FEV(1) of <80% predicted but also in 41% of those with an FEV(1) of >/=80% predicted. Only 5% of patients had a substantial bronchodilator response suggesting a diagnosis of asthma. Emphysema was present in 51% of patients and confined to the upper lobes in most (73% of these patients). HRCT evidence of bronchiectasis was noted in 29% of patients and was predominantly tubular; most (81%) were current or ex-smokers. A solitary pulmonary nodule was seen on 9% of scans and unsuspected lung malignancy was diagnosed in two patients. CONCLUSIONS: This study confirms that COPD in primary care is a heterogeneous condition. Some patients do not fulfil the proposed diagnostic criteria with FEV(1) of >/=80% predicted but they may nevertheless have airflow obstruction. Bronchiectasis is common in this group of patients, as is unsuspected malignancy. These findings should be considered when developing recommendations for the investigation and management of COPD in the community.

Adult↗
PubMed2000

Role of core temperature as a stimulus for cold acclimation during repeated immersion in 20 degrees C water.

The relative importance of skin vs. core temperature for stimulating cold acclimation (CA) was examined by 5 wk of daily 1-h water immersions (20 degrees C) in resting (RG) and exercising (EG) subjects. Rectal temperature fell (0.8 degrees C; P < 0.05) during immersion only in RG. Skin temperature fell (P < 0.05) similarly in both groups. Physiological responses during cold-air exposure (90 min, 5 degrees C) were assessed before and after CA. Body temperatures and metabolic heat production were similar in both groups with no change due to CA. Cardiac output was lower (P < 0.05) in both groups post-CA (10.4 +/- 1.2 l/min) than pre-CA (12.2 +/- 1. 0 l/min), but mean arterial pressure was unchanged (pre-CA 107 +/- 2 mmHg, post-CA 101 +/- 2 mmHg). The increase in norepinephrine was greater (P < 0.05) post-CA (954 +/- 358 pg/ml) compared with pre-CA (1,577 +/- 716 pg/ml) for RG, but CA had no effect on the increase in norepinephrine for EG (pre-CA 1,288 +/- 438 pg/ml, post-CA 1,074 +/- 279 pg/ml). Skin temperature reduction alone may be a sufficient stimulus during CA for increased vasoconstrictor response, but core temperature reduction appears necessary to enhance sympathetic activation during cold exposure.

Adaptation, Physiological↗
PubMed2000

Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD.

STUDY OBJECTIVES: To stratify COPD patients presenting with an acute exacerbation on the basis of sputum color and to relate this to the isolation and viable numbers of bacteria recovered on culture. DESIGN: Open, longitudinal study of sputum characteristics and acute-phase proteins. SETTING: Patients presenting to primary-care physicians in the United Kingdom. Patients were followed up as outpatients in specialist clinic. PATIENTS: One hundred twenty-one patients with acute exacerbations of COPD were assessed together with a single sputum sample on the day of presentation (89 of whom produced a satisfactory sputum sample for analysis). One hundred nine patients were assessed 2 months later when they had returned to their stable clinical state. INTERVENTIONS: The expectoration of green, purulent sputum was taken as the primary indication for antibiotic therapy, whereas white or clear sputum was not considered representative of a bacterial episode and the need for antibiotic therapy. RESULTS: A positive bacterial culture was obtained from 84% of patients sputum if it was purulent on presentation compared with only 38% if it was mucoid (p < 0.0001). When restudied in the stable clinical state, the incidence of a positive bacterial culture was similar for both groups (38% and 41%, respectively). C-reactive protein concentrations were significantly raised (p < 0.0001) if the sputum was purulent (median, 4.5 mg/L; interquartile range [IQR], 6. 2 to 35.8). In the stable clinical state, sputum color improved significantly in the group who presented with purulent sputum from a median color number of 4.0 (IQR, 4.0 to 5.0) to 3.0 (IQR, 2.0 to 4. 0; p < 0.0001), and this was associated with a fall in median C-reactive protein level to 2.7 mg/L (IQR, 1.0 to 6.6; p < 0.0001). CONCLUSIONS: The presence of green (purulent) sputum was 94.4% sensitive and 77.0% specific for the yield of a high bacterial load and indicates a clear subset of patient episodes identified at presentation that is likely to benefit most from antibiotic therapy. All patients who produced white (mucoid) sputum during the acute exacerbation improved without antibiotic therapy, and sputum characteristics remained the same even when the patients had returned to their stable clinical state.

Acute Disease↗
PubMed2000

Physiological problems associated with wearing NBC protective clothing during cold weather.

This report considers how thermal balance of soldiers wearing nuclear, biological and chemical (NBC) protective clothing in combination with the Extreme Cold Weather Clothing System (ECWCS) is affected during work in cold weather. A review of published reports concerning physiological consequences of wearing NBC protective clothing during cold exposure was completed. The findings reported in the experimental literature were too limited to adequately forecast the effects of adding NBC clothing to ECWCS. To remedy the information gap, simulation modeling was employed to predict body temperature changes during alternating bouts of exercise and rest throughout 8 h of exposure to three different severely cold conditions. Published findings indicate that NBC protective clothing may inadequately protect against hand and finger cooling, especially during rest following strenuous activity. No evidence substantiates suggestions that wearing NBC protective masks increases susceptibility to facial frostbite. Collectively, the limited experimental work and the results of simulation modeling argue against any increased risk of hypothermia associated with wearing NBC protective clothing while working in the cold. However, wearing NBC protective clothing during strenuous activity in cold weather may increase the risk of hyperthermia, and cause sweat accumulation in clothing which may compromise insulation and increase the risk of hypothermia during subsequent periods of inactivity.

Body Temperature↗
PubMed2000

Distribution of glucocorticoid and mineralocorticoid receptors and 11beta-hydroxysteroid dehydrogenases in human and rat ocular tissues.

PURPOSE: The administration of glucocorticoids as topical or systemic medications may lead to the development of ocular hypertension through the induction of morphologic and biochemical changes in the trabecular meshwork leading to a reduction in the facility of aqueous outflow. Glucocorticoids exert their physiological effects by binding to and activating glucocorticoid and mineralocorticoid receptors. The activity of glucocorticoids is critically regulated at a prereceptor level by the two isozymes of 11beta-hydroxysteroid dehydrogenase. The purpose of this study was to determine the distribution of glucocorticoid target receptors and the isozymes of 11beta-hydroxysteroid dehydrogenase (11 beta-HSD) that regulate the activity of glucocorticoids at a prereceptor level in human and rat ocular tissues. METHODS: Horizontal sections of normal adult human and rat eyes were cut and hybridized with 35S-labeled cRNA probes specific for the glucocorticoid receptor, mineralocorticoid receptor, and 11beta-HSD types 1 and 2 using in situ hybridization. Immunohistochemical analysis of glucocorticoid and mineralocorticoid receptors using monoclonal antibodies was carried out on rat eye tissue sections. Whole rat eyes were homogenized and the activity of 11beta-HSD types 1 and 2 in the eye assessed as the percentage conversion of tritiated corticosterone to tritiated 11-dehydrocortico-sterone when corticosterone was added to the homogenate. RESULTS: In the rat ocular tissues mRNAs encoding glucocorticoid receptor, mineralocorticoid receptor, and 11beta-HSD types 1 and 2 were detected in nonpigmented ciliary epithelium, trabecular meshwork, corneal epithelium and endothelium, and anterior lens epithelium. Immunohistochemistry confirmed the presence of glucocorticoid and mineralocorticoid receptors at these sites. Activity of both isozymes of 11beta-HSD was demonstrated in homogenized rat eyes (percentage conversion of tritiated corticosterone to 11-dehydrocorticosterone; mean +/- SD, 11beta-HSD 1 = 15% +/- 5.3%, 11beta-HSD 2 = 7.9% +/- 2.8%). In both human and rat eyes, expression of mRNAs encoding glucocorticoid receptor and 11beta-HSD type 1 was high in the trabecular meshwork and lens epithelium, whereas expression of mRNAs encoding the mineralocorticoid receptor and 11beta-HSD type 2 was high in nonpigmented ciliary epithelium and corneal epithelium and endothelium. CONCLUSIONS: Glucocorticoid target receptors and the enzymes regulating glucocorticoid activity at these receptors are present in mammalian ocular tissues, which regulate aqueous humor formation and outflow. Alteration in the number or affinity of receptors or in the activity of regulatory enzymes may alter the susceptibility of certain individuals to the effects of glucocorticoids on intraocular pressure.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

Combating information overload: a six-month pilot evaluation of a knowledge management system in general practice.

A six-month prospective study was conducted on the usefulness and usability of a representative electronic knowledge management tool, the WAX Active Library, for 19 general practitioners (GPs) evaluated using questionnaires and audit trail data. The number of pages accessed was highest in the final two months, when over half of the access trails were completed within 40 seconds. Most GPs rated the system as easy to learn, fast to use, and preferable to paper for providing information during consultations. Such tools could provide a medium for the activities of knowledge officers, help demand management, and promote sharing of information within primary care groups and across NHSnet or the Internet.

Adult↗
PubMed1999

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with type A-resistant cervical dystonia (CD). BACKGROUND: Local intramuscular injections of BoNT are an effective therapy for CD. After repeated use, some patients become resistant to therapy. BoNT/B, effective in type A toxin-responsive patients, is proposed as an alternative therapy for type A-resistant patients. METHODS: The authors performed a 16-week, double-blind, placebo-controlled trial of BoNT/B in type A-resistant patients with CD. After resistance to therapy was confirmed with the frontalis-type A test, placebo or 10,000 U BoNT/B was administered in a single session into two to four clinically involved muscles. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was the primary efficacy measurement. TWSTRS-Total, three visual analog scales (Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, Patient Analog Pain Assessment), and adverse events were assessed at baseline and weeks 2, 4, 8, 12, and 16. RESULTS: A total of 77 patients participated (38 placebo, 39 active). Improvements in severity, disability, and pain were documented in the BoNT/B-treated group. TWSTRS-Total scores were improved in the BoNT/B-treated group at weeks 4 (p = 0.0001), 8 (p = 0.0002), and 12 (p = 0.0129). All three visual analog scales demonstrated improvements at week 4 (p < 0.0001, 0.0001, and 0.001). A Kaplan-Meier analysis supported a duration of effect of 12 to 16 weeks in the active group. Dry mouth and dysphagia were self-limited adverse effects, reported more commonly in the BoNT/B group. CONCLUSIONS: Botulinum toxin type B (BoNT/B) (NeuroBloc) is safe and efficacious for the management of patients with type A-resistant cervical dystonia with an estimated duration of treatment effect of 12 to 16 weeks.

Adult↗
PubMed1999

Hyperimmune bovine colostrum specific for recombinant Cryptosporidium parvum antigen confers partial protection against cryptosporidiosis in immunosuppressed adult mice.

Preparturient cows were immunized three times over a six-week period with recombinant plasmid DNA encoding the Cryptosporidium parvum CP15/60 antigen by injecting the DNA in the mammary gland. Serum was collected at each immunization and first colostrum was collected after parturition; all were assayed for Cryptosporidium-specific antibodies (Ab). A serological response to C. parvum sporozoite and oocyst antigen was detected in cows immunized with pCP15/60 plasmid DNA. Colostrum from these cows, unlike colostrum from normal controls, contained Ab specific for C. parvum sporozoites and oocysts as indicated by immunofluorescence Ab (IFA) staining. Colostrum was also tested for conferring passive immunity against C. parvum infection by oral administration to immunosuppressed adult inbred mice. Immune colostrum and control colostrum were administered to separate groups of dexamethasone (DEX)-treated adult C57BL/6NCr mice beginning 12 h before and at 12 h intervals for 3 days after oral C. parvum oocyst infection. Cryptosporidium development was assayed in ilea of immune- and control-colostrum-treated mice 96 h postinfection by semiquantitative PCR. Mice receiving immune colostrum showed partial protection (about 50% reduction) against intestinal C. parvum development compared to mice receiving control colostrum. This protection was evident at a challenge dose of 10(3) C. parvum oocysts per mouse; no differences were noted in parasite development between groups receiving immune or control colostrum and infected with 10(4) oocysts. This study showed that serum and colostrum Ab response to C. parvum can be elicited in preparturient cows by direct injection of recombinant pCP15/60 plasmid DNA and that passive protection against cryptosporidiosis can be obtained by treating immunosuppressed mice with immune colostrum before and after C. parvum infection.

Animals↗
PubMed1999

Thrombocytopenia after liver transplantation.

BACKGROUND: Thrombocytopenia after orthotopic liver transplantation (OLT) is a well recognized and prevalent early postoperative complication. The etiology, as well as the effect of this phenomenon on transplant outcome, however, are vague. The aims of this study are to identify factors contributing to thrombocytopenia and to ascertain whether there is any correlation with early rejection and ultimate survival. METHODS: This study examines 541 OLTs (541 grafts in 494 patients) that were transplanted at the University of Miami during the 3-year period from June 1994 to September 1997. The patients with severe postoperative thrombocytopenia (nadir platelet count [PLT] < 20,000/mm3), as well as the whole group of patients, were analyzed. The preoperative PLT, intra-operative platelet transfusion requirements, cross-match, recipient and donor cytomegalovirus (CMV) status, infusion of donor bone marrow cells (DBMC), occurrence of early rejection episodes (in the first posttransplant month), and re-transplantation were factors examined for any association with thrombocytopenia. Total bilirubin (TB) and direct bilirubin (dB), hematocrit, white blood cell count (WBC), aspartate aminotransferase and alanine aminotransferase, determined on the day that platelets reached a nadir (nadir day), were also analyzed. RESULTS: In 90.9% of the cases, there was a 56.5%+/-23.5% fall in platelets in the immediate posttransplant period (first 2 weeks), but the mean PLT exceeded preoperative levels during the 3rd and 4th postoperative weeks. The nadir of the drop in the PLT most commonly occurred on posttransplant day 4. For preoperative PLT, platelet transfusions during the operation, re-transplantation, early rejection, cross-match, and recipient CMV status, there was significant statistical correlation with any degree of postoperative thrombocytopenia. Four of these factors, preoperative PLT, intra-operative platelet transfusions, re-transplantation, and early rejection, were found to be independently associated with thrombocytopenia in general. None of them was found to be independently correlated with severe thrombocytopenia. A statistically significant correlation between bilirubin and WBC on the nadir day and the degree of thrombocytopenia was observed. No correlation was found between infusion of DBMC or donor CMV serology and thrombocytopenia. Both the nadir PLT and the percentage of the platelet fall were independent predictive factors (p<0.01 and 0.005, respectively) of patient and graft survival. CONCLUSIONS: Thrombocytopenia in the immediate posttransplant period is correlated with low preoperative PLT, massive platelet transfusions, and re-transplantation. These factors reflect a poor preoperative condition. There is also a correlation with allograft dysfunction, rejection, and poorer patient and graft survival. A rise in the mean PLT after the 2nd postoperative week reflects proper graft function.

Adolescent↗
PubMed1999

Bioimpedance assessment of hypohydration.

PURPOSE: This study examined the utility of bioimpedance spectroscopy (BIS) for assessing total body water (TBW) changes associated with moderate (6-7% TBW), hypertonic (HH), and isotonic (IH) hypohydration. METHODS: The TBW of nine men was measured using BIS (TBWBIS) when euhydrated (EU) and during HH and IH. These measurements were compared with TBW measurements obtained using isotope dilution (deuterium oxide; TBWD20) during EU, and the estimated TBWD20 during hypohydration calculated from body weight change. RESULTS: Body weight loss was similar (P > 0.05) for HH (3.4 +/- 0.7 kg) and IH (2.9 +/- 0.7 kg). Plasma osmolality was higher (P < 0.05) on HH (292 +/- 4 mOsmol x kg(-1)) than EU (280 +/- 4 mOsmol x kg(-1)) and IH (284 +/- 3 mOsmol x kg(-1)), and higher (P < 0.05) during IH than EU. The measurements reflected a similar decrease (P < 0.05) in TBW during HH (TBWD20: 45.4 +/- 7.3 L, TBWBIS: 42.2 +/- 5.1 L) and IH (TBWD20: 45.8 +/- 7.5 L, TBWBIS: 42.0 +/- 4.9 L), compared with EU (TBWD20: 48.8 +/- 7.5 L, TBWBIS: 44.3 +/- 5.0 L), but TBWD20 was consistently higher (3.9 +/- 4.0 L, P < 0.05) than TBWBIS during all tests. TBWD20 and TBWBIS were correlated (P < 0.05) during EU (r = 0.87), HH (r = 0.84), and IH (r = 0.84). The change in TBW from EU during HH was greater (P < 0.05) for TBWD20 (3.5 +/- 0.8 L) than TBWBIS (2.1 +/- 0.9 L), but during IH the change in TBW reflected by TBWD20 (3.0 +/- 0.6 L) and TBWBIS (2.3 +/- 0.8 L) did not differ. The change in TBWD20 and TBWBIS between EU and hypohydration was correlated for HH (r = 0.77, P < 0.05), but not IH. CONCLUSION: These findings indicate that BIS is sufficiently sensitive to detect moderate hypohydration; however, the resolution of this technique diminished with isotonic fluid loss.

Adolescent↗
PubMed1999

Patients' perception of visual impairment in glaucoma: a pilot study.

BACKGROUND/AIMS: There is a paucity of useful information on the level of visual disability suffered by glaucoma patients. The aims of this study were to determine and rank the frequency of self reported visual disability in daily tasks performed by glaucoma patients; to examine the interrelation between disabilities using factor analysis; to study the relation between perceived visual difficulty and a measure of the severity of visual field loss; to develop a glaucoma specific subgroup of questions; and examine the validity and reliability of this subgroup of questions. METHODS: 63 glaucoma patients completed a questionnaire containing 62 questions covering 10 broad aspects of daily life activities using a five point answer scale. Patients were classified into three groups as having mild, moderate, and severe field loss on the basis of the perimetric results. The relation between a measure of the severity of visual field loss and subjective visual disability in the three groups was examined. RESULTS: Using factor analysis, the most frequently reported problems were grouped into the following four categories: outdoor mobility, glare and lighting conditions and activities demanding functional peripheral vision, household tasks, and personal care. These four factors accounted for 72% of the variability in the patients' questionnaire responses. With increasing severity of binocular visual field loss there was an increase in the number of self reported visual problems. A loss of confidence in performing some routine daily tasks tended to precede self reported specific visual disabilities. The factor "glare and lighting and activities demanding functional peripheral vision" was found to have a significant relation with a measure of visual field loss and was used to create a glaucoma specific subset of questions. Cronbach's alpha showed a high degree of reliability and internal consistency (alpha =0.96) in this glaucoma specific subset of questions. Furthermore, the validity of this new subset of questions was shown to be significant (r=0.037, p<0.05) for the correlation between a measure of the severity of binocular visual field loss and the mean score of the variables used in the glaucoma specific subgroup of questions. CONCLUSIONS: Outcome measures and quality of life issues need to be addressed in glaucoma. This pilot study identified common problems encountered by patients which at the present time are not assessed in routine glaucoma care. It also identified a subgroup of questions that seems to be specific for glaucoma. Further research is required if a significant impact on the quality of life of glaucoma patients is to be achieved.

Aged↗
PubMed1999

Evaluating physiological strain during cold exposure using a new cold strain index.

A cold strain index (CSI) based on core (T(core)) and mean skin temperatures (T(sk)) and capable of indicating cold strain in real time and analyzing existing databases has been developed. This index rates cold strain on a universal scale of 0-10 and is as follows: CSI = 6.67(T(core t) - T(core 0)). (35 - T(core 0))(-1) + 3.33(T(sk (t)) - T(sk 0)). (20 - T(sk 0))(-1), where T(core 0) and T(sk 0) are initial measurements and T(core t) and T(sk t) are simultaneous measurements taken at any time t; when T(core t) > T(core 0), then T(core t) - T(core 0) = 0. CSI was applied to three databases. The first database was obtained from nine men exposed to cold air (7 degrees C, 40% relative humidity) for 120 min during euhydration and two hypohydration conditions achieved by exercise-heat stress-induced sweating or by ingestion of furosemide 12 h before cold exposure. The second database was from eight men exposed to cold air (10 degrees C) immediately on completion of 61 days of strenuous outdoor military training, 48 h later, and after 109 days. The third database was from eight men repeatedly immersed in 20 degrees C water three times in 1 day and during control immersions. CSI significantly differentiated (P < 0.01) between the trials and individually categorized the strain of the subject for two of these three databases. This index has the potential to be widely accepted and used universally.

Adult↗
PubMed1999

Blood flow velocity in the peripheral circulation of glaucoma patients.

Using the laser Doppler technique we measured finger blood flow velocity in 25 untreated primary open-angle glaucoma (POAG), 22 untreated low-tension glaucoma (LTG) and 19 age-matched normal subjects. Four blood flow measurements were recorded: baseline flow, after immersion in warm water for 2 min (40 degrees C maximum flow), after 10 s exposure to cold water (4 degrees C minimum flow) and time to recover to baseline flow after cold immersion. Significant differences between the LTG group and both the normal and POAG groups were found in a greater maximum flow (p = 0.03 and p = 0.01, respectively), a lower minimum flow (p = 0.04 and p = 0.03, respectively) and a longer recovery time to baseline flow (p = 0. 0001 for both the normal and POAG groups). A longer recovery time to baseline flow (p = 0.008) in POAG was the only difference between the normal and POAG groups. Both glaucoma groups had more systemic vascular disease than normal, and there were more smokers in the POAG group than normals. Subgroup assessment performed with migraine, vascular disease and smoking subjects excluded from the analysis did not alter the overall results. We conclude that systemic vasospasm is a strong feature of low-tension glaucoma.

Aged↗
PubMed1999

The anatomy of a crisis. One perspective.

In this article, the author analyzes the influx of breast implant class action lawsuits in the past decade. He discusses the responses of the medical community and the manufacturers as well as the impact the media has had on this issue. The author recounts the steps he took in his representation of the defense and examines the significance of these lawsuits for the industry and the general public.

Breast Implantation↗
PubMed1999

Growth of human tumor cells in macroporous microcarriers results in p53-independent, decreased cisplatin sensitivity relative to monolayers.

Multicellular contact has been shown to influence the in vitro sensitivity of cells to drug treatment. We investigated the use of macroporous gelatin microcarriers, CultiSpher-G, as a convenient laboratory system for the molecular analysis of this "contact effect". We determined that human A549 cells can be grown in CultiSphers with growth and cell cycle parameters similar to those of monolayers. In addition, cells in CultiSphers express less p27/kip1, an indicator of cell cycle arrest, than equivalent cells in monolayers. When treated with drugs, A549 cells grown in CultiSphers or monolayers accumulate equivalent amounts of platinum-DNA adducts and similar amounts of doxorubicin. Moreover, A549 and KB-3-1 cells in CultiSphers have significantly decreased sensitivity to cis-platinum(II)diammine dichloride (cisplatin), 4-hydroperoxycyclophosphamide, doxorubicin, and paclitaxel (taxol) compared with cells in monolayers when assayed by clonogenic survival. Cisplatin treatment in monolayers or CultiSphers did not result in apoptotic cell death. In contrast, paclitaxel caused a significant amount of sub-G1 DNA, an indicator of apoptosis, which was diminished when cells were grown in CultiSphers compared with monolayers. When grown in CultiSphers, cells with abrogated p53 function (A549/16E6 and NCI-H1299) were less sensitive to cisplatin than the corresponding monolayer cells, indicating that the decrease in sensitivity is p53 independent. Taken together, the data suggest that CultiSpher-G microcarriers are a useful in vitro system to examine the effects of three-dimensional cell contact on drug sensitivity of human tumor cells.

Antineoplastic Agents↗