ABSTRACT
Results of a community HIV testing pilot (fasTest) targeting men who have sex with men (MSM) in Brighton are reported and service users are compared with those testing in genitourinary medicine (GUM) clinics. FasTest offers rapid HIV testing in a weekly evening drop-in session staffed by GUM professionals in a community organisation. It was prospectively evaluated from November 2004 to March 2006 using a self-completed paper questionnaire assessing demographics, previous use of GUM, HIV testing history and sexual behaviour. Follow-up through GUM/HIV services was monitored. A simplified questionnaire was completed by MSM accessing the GUM clinic over the same time period. Men were included in the analysis if they identified as gay or bisexual or had recent sex with a man, tested for HIV and received a result. In both the fastest and GUM groups, men reported high rates of unprotected anal sex in the last 3 months. fasTest clients were significantly younger and less likely to test positive for HIV. This difference was independent of age and HIV testing history. There was no difference in rates of recent infection between the two. We conclude that community HIV testing is feasible and reaches the target group of high risk MSM.
Subject(s)
Ambulatory Care Facilities/statistics & numerical data , Community Health Services/statistics & numerical data , HIV Infections/diagnosis , Patient Acceptance of Health Care/statistics & numerical data , Adult , England/epidemiology , HIV Infections/epidemiology , Humans , Male , Middle Aged , Pilot Projects , Program Evaluation , Sexual Behavior , Young AdultABSTRACT
The effects of glycerol and moisture contents on the thermal transitions of whey protein isolate (WPI) powder-glycerol-water mixtures were studied. Mixtures with ratios of 100:0, 70:30, 60:40, and 50:50 WPI:glycerol on a dry basis (db) were preconditioned to 0.34 +/- 0.01 (25.4 +/- 0.4 degrees C) and 0.48 +/- 0.02 (25.9 +/- 2.2 degrees C) water activity. Differential scanning calorimetry (DSC) showed the existence of an endothermic peak starting at 148.3 +/- 0.7 degrees C for 100% WPI preconditioned to a water activity of 0.34 +/- 0.01. The onset temperature of this peak decreased with addition and increase of glycerol content, as well as with the increase in water activity from 0.34 +/- 0.01 to 0.48 +/- 0.02. An additional endothermic transition, important for extruding the mixtures into flexible sheets, occurred in mixtures containing 50% glycerol db, preconditioned to 0.48 +/- 0.02 water activity. The onset temperature of the peak was 146 +/- 2.0 degrees C. Whey protein-based sheets containing 45.8%, 48.8%, and 51.9% glycerol db were obtained using a Haake-Leistritz corotating twin-screw extruder. All samples were obtained at a screw speed of 250 rpm and a final barrel-temperature profile of 20, 20, 20, 80, 110, and 130 degrees C. Melt temperature at the time of sheet formation was 143 to 150 degrees C. Average thickness of the sheets was 1.31 +/- 0.02 mm. Samples with 45.8% glycerol db had significantly higher tensile strength (TS) than samples with higher glycerol contents. Also, as glycerol concentration increased, sheet elastic modulus (EM) decreased significantly (P= 0.05). Extrusion of whey protein-based sheets is an important step toward extrusion of thinner edible films for food wraps, layers, or pouches.
Subject(s)
Glycerol , Hot Temperature , Milk Proteins/chemistry , Plasticizers , Calorimetry, Differential Scanning , Color , Food Handling/methods , Tensile Strength , Thermodynamics , Water/analysis , Whey ProteinsSubject(s)
Cardiac Tamponade/etiology , Heart Aneurysm/complications , Heart Defects, Congenital/complications , Heart Rupture/complications , Adult , Angiocardiography , Cardiac Surgical Procedures/methods , Cardiac Tamponade/diagnostic imaging , Cardiac Tamponade/surgery , Female , Heart Aneurysm/diagnostic imaging , Heart Aneurysm/surgery , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/surgery , Heart Rupture/surgery , Heart Ventricles/pathology , Heart Ventricles/surgery , Humans , Magnetic Resonance Imaging , Thoracotomy , Treatment OutcomeABSTRACT
OBJECTIVE: To evaluate the safety, efficacy, and feasibility of the technician run open access exercise electrocardiography service at Freeman Hospital. DESIGN: Questionnaire analysis of the responses of the general practitioners of randomly selected patients who used the service. SETTING: A tertiary care cardiac centre, providing an open access service to general practitioners in the community. PATIENTS: 269 patients randomly selected from 552 who underwent open access exercise electrocardiography over a 2.5 year period. OUTCOME MEASURES: Utilisation of service: the reasons for referral, whether the service was optimally used by the general practitioners, and its effect on their management practice; effect on number of cardiology referrals; benefit to the patients; safety, efficacy, and feasibility of a technician run service; general practitioners' assessment of the service. RESULTS: 147 of 178 general practitioners (82.6%) responded to the questionnaire, on 247 of 269 patients (91. 8%). General practitioners used the service for diagnosing ischaemic heart disease in 72.5% of cases, for prognostic purposes in 17.8%, or both in 5.3%. In 197 cases (79.8%), the general practitioners felt that the service had changed the way they managed their patients. The exercise test was positive in 90 patients (36.5%) and identified 38 as at high risk. The service was effective in optimising the cardiology service by reducing referrals by 47%. CONCLUSIONS: The service was used by general practitioners primarily for diagnosing ischaemic heart disease and not so often for prognosis. The utilisation of the service was optimal as assessed by the high positivity rate. The service meets its primary objective of assisting general practitioners in the management of patients with suspected ischaemic heart disease, and may have helped to optimise resources by reducing the number of referrals to cardiologists. It has helped prioritize patient management and may have benefited high risk patients by facilitating rapid identification and referral. It can be run safely and effectively by trained technicians.
Subject(s)
Allied Health Personnel , Cardiology Service, Hospital/organization & administration , Electrocardiography , Health Services Accessibility/organization & administration , Myocardial Ischemia/diagnosis , Adult , Age Distribution , Aged , Aged, 80 and over , England , Exercise Test , Family Practice/organization & administration , Feasibility Studies , Female , Humans , Male , Middle Aged , Referral and Consultation/organization & administration , Sex Distribution , Surveys and QuestionnairesABSTRACT
The primary concern in food safety issues focuses on microorganisms and microbial toxins. Effective food preservation requires that the growth and proliferation of hazardous microorganisms be well controlled, and that the presence of significant quantities of microbial toxins in foods be prevented. The traditional effective preservation methodologies, such as canning, are being supplemented by new technologies which are less destructive of the food qualities. New strategies are therefore needed to prevent the transmission of microbial contamination or to prevent the formation of microbial toxins which remain in food. This paper discusses the role of modern processing methodologies in helping protect consumers from hazards of microbial origin.
Subject(s)
Bacterial Toxins/adverse effects , Food Microbiology , Food-Processing Industry , Foodborne Diseases/prevention & control , Food Irradiation , Food Preservation , Frozen Foods , Hot Temperature , Humans , Hydrogen-Ion Concentration , Microwaves , Refrigeration , Water/chemistryABSTRACT
OBJECTIVE: To provide and evaluate telemedicine services for rural physicians and patients in Nova Scotia. MATERIALS AND METHODS: As a pilot project, three telemedicine services (videoconference continuing medical education [CME], teledermatology, and teleradiology) were provided to four hospitals in Nova Scotia communities. All four sites received CME (a total of 269 physicians, 53 other health care professionals); three sites received teledermatology (66 consultations), and two sites received teleradiology (808 radiologic examinations). At the consulting site, 12 faculty members presented 24 one-hour videoconferences, and there was one consulting radiologist and dermatologist. Each service was evaluated independently. Methods included participant questionnaires; focus groups; numbers and categories of participants or examinations; comparison of operational costs, capitol costs (teledermatology and teleradiology), and travel costs (CME); technical assessments of hardware, software, and telecommunications; assessment of clinical diagnostic procedures (teledermatology); and comparative study of original and digitized films (teleradiology). RESULTS: Despite growing pains, the technologies effectively provided the three services: the services were acceptable to referring and consulting physicians and patients. Improvements in patient care and outcomes comparable to those of traditional methods were demonstrated in teleradiology and teledermatology, especially for emergencies. Physician access to CME and patient access to dermatology consultation services were improved. Financial savings were demonstrated for CME, but further investigation is required to determine the savings attributable to teleradiology and teledermatology. CONCLUSIONS: The telemedicine services supported rural physicians, their patients, and their communities. Although telemedicine is not a panacea for all concerns of rural physicians, the pilot project provided a strong foundation for further development and study.
Subject(s)
Telemedicine , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Education, Medical, Continuing , Female , Humans , Infant , Male , Middle Aged , Nova Scotia , Pilot Projects , Rural Population , TeleradiologyABSTRACT
The aim of this study was to describe the sexual behaviour of men who had sex with both men and women in the preceding five years (behaviourally bisexual men), specifically to examine their needs in relation to HIV prevention. Anonymous telephone interviews were carried out with respondents recruited though advertisements in UK newspapers and magazines with (sexual) 'personal' or 'contact' sections. Data are reported from 745 respondents. Respondents report relatively high and approximately equal numbers of male and female sexual partners in the year preceding interview. There is a clear patterning of sexual activity by type of partner (regular or casual). A high proportion report anal intercourse with female and male partners. A third disclose their homosexual practices to regular female partners. Although self-reported HIV seroprevalence is low (less than 1%), the levels of unprotected sex with multiple sexual partners indicate substantial potential for transmission of sexually transmitted infections, including HIV. While low seroprevalence suggests that there is little overlap with existing core groups of HIV infection, the study provides information to judge the priority of targeting HIV prevention initiatives and suggests ways in which initiatives could be undertaken.
PIP: Findings are reported from an investigation of the sex and HIV risk reduction behaviors during the past 5 years of behaviorally bisexual men in the UK, men who have sex with both men and women regardless of their stated sexual identity. Anonymous telephone interviews were conducted with 745 respondents recruited through advertisements in UK newspapers and magazines with sexual "personal" or "contact" sections. The final sample of respondents from 107 postcode regions of the country was obtained from 60,368 ineffective calls and 7398 effective calls made to the survey hotline over an 8-week period. The men were 16-73 years old, of median and mean ages 32 and 33.3 years, respectively. The sample closely approximated the UK general population of men in terms of educational status and social and occupational classes, but slightly under-represented Blacks, other ethnic minorities, and married men. 1 man reported being diagnosed with HIV infection and 9.1% had attended a STD clinic in the preceding year. In the year before the interview, although 94.7% had female partners and 91.9% had male partners, only 43.9% described themselves as bisexual and less than 1% identified as gay or homosexual. The men more often reported having regular female partners than regular male partners, and casual female partners were reported by more men than casual male partners. 67.1% of the 93.8% of men who reported having vaginal intercourse used no condom. 22.6% of the 44.4% of men who reported having anal intercourse with women used no condom. 18.2% of the 62.2% men who had anal sex with men used no condom. 33% disclose their homosexual behavior to regular female partners.
Subject(s)
Bisexuality , HIV Infections/psychology , Adolescent , Adult , Aged , Awareness , Coitus , Condoms/statistics & numerical data , Contact Tracing , Female , Humans , Male , Middle Aged , Risk-Taking , Sexual Partners , Truth DisclosureABSTRACT
Simple sugars, especially disaccharides, stabilize biomaterials of various composition during air-drying or freeze-drying. We and others have provided evidence that direct interaction, an interaction that we believe is essential for the stabilization, between the sugar and polar groups in, for example, proteins and phospholipids occurs in the dry state. Some researchers, however, have suggested that the ability of the sugar to form a glass is the only requirement for stabilization. More recently, we have shown that both glass formation and direct interaction of the sugar and headgroup are often required for stabilization. In the present study, we present a state diagram for trehalose glass and suggest that the efficacy of this sugar for stabilization may be related to its higher glass transition temperatures at all water contents. We also show that trehalose and trehalose:liposome preparations form trehalose dihydrate as well as trehalose glass when rehydrated with water vapor. Formation of the dihydrate sequesters water, which might otherwise participate in lowering the glass transition temperature to below ambient. Because samples remain in the glassy state at ambient temperatures, viscosity is high and fusion between liposomes is prevented.
Subject(s)
Liposomes , Phosphatidylcholines/chemistry , Preservatives, Pharmaceutical , Trehalose , Calorimetry, Differential Scanning , Drug Stability , Fluoresceins , Fluorescent Dyes , Freeze Drying , Kinetics , Spectrometry, Fluorescence , Sucrose , ThermodynamicsABSTRACT
OBJECTIVES: To examine aggregate changes in homosexual HIV risk-taking among gay men attending the Gay Pride festival in the United Kingdom over a 3-year period during which HIV prevention activity targeted at this population increased considerably. DESIGN: Three cross-sectional self-completion questionnaires at yearly intervals asking identical questions on sexual behaviour in the preceding year. SETTING: Lesbian and Gay Pride festival held in London, June 1993, 1994 and 1995. PARTICIPANTS: Men attending the festival who were UK resident, had ever had sex with another man and who were willing to fill out a questionnaire (n = 1620, 1753 and 1168 in 1993, 1994 and 1995, respectively). MAIN OUTCOME MEASURES: Self-reported numbers of sexual partners, sexual partners with whom anopenile intercourse occurred and sexual partners with whom anopenile intercourse occurred without a condom. RESULTS: Over the 3-year period there were no changes in the proportion of men engaging in any of the sexual behaviour measures. At each cross-section, one in three men (514 out of 1566, 511 out of 1612, 351 out of 1059 in 1993, 1994 and 1995, respectively) had engaged in anopenile intercourse without a condom with at least one male partner in the preceding year and one in 10 (162 out of 1566, 156 out of 1612, 103 out of 1059 in 1993, 1994 and 1995, respectively) had done so with more than one male partner. CONCLUSION: Despite an increase in prevention work targeted at this population, aggregate levels of sexual risk-taking have remained very stable. A reassessment of the efficacy of current HIV prevention messages and methods with this population is urgently required.
Subject(s)
HIV Infections/psychology , Risk-Taking , Adult , Condoms , Cross-Sectional Studies , HIV Infections/epidemiology , HIV Infections/prevention & control , Holidays/psychology , Homosexuality, Male/psychology , Humans , Male , Surveys and Questionnaires , United Kingdom/epidemiologyABSTRACT
A major goal of experimental and clinical hematology is the identification of mechanisms and conditions that support the expansion of transplantable hematopoietic stem cells. In normal marrow, such cells appear to be identical to (or represent a subset of) a population referred to as long-term-culture-initiating cells (LTC-ICs) so-named because of their ability to produce colony-forming cell (CFC) progeny for > or = 5 weeks when cocultured with stromal fibroblasts. Some expansion of LTC-ICs in vitro has recently been described, but identification of the factors required and whether LTC-IC self-renewal divisions are involved have remained unresolved issues. To address these issues, we examined the maintenance and/or generation of LTC-ICs from single CD34+ CD38- cells cultured for variable periods under different culture conditions. Analysis of the progeny obtained from cultures containing a feeder layer of murine fibroblasts engineered to produce steel factor, interleukin (IL)-3, and granulocyte colony-stimulating factor showed that approximately 20% of the input LTC-ICs (representing approximately 2% of the original CD34+ CD38- cells) executed self-renewal divisions within a 6-week period. Incubation of the same CD34+ CD38- starting populations as single cells in a defined (serum free) liquid medium supplemented with Flt-3 ligand, steel factor, IL-3, IL-6, granulocyte colony-stimulating factor, and nerve growth factor resulted in the proliferation of initial cells to produce clones of from 4 to 1000 cells within 10 days, approximately 40% of which included > or = 1 LTC-IC. In contrast, in similar cultures containing methylcellulose, input LTC-ICs appeared to persist but not divide. Overall the LTC-IC expansion in the liquid cultures was 30-fold in the first 10 days and 50-fold by the end of another 1-3 weeks. Documentation of human LTC-IC self-renewal in vitro and identification of defined conditions that permit their extensive and rapid amplification should facilitate analysis of the molecular mechanisms underlying these processes and their exploitation for a variety of therapeutic applications.
Subject(s)
Culture Media, Serum-Free/pharmacology , Hematopoietic Stem Cells/cytology , Animals , Bone Marrow Cells , Cell Division/drug effects , Cell Survival , Cells, Cultured , Coculture Techniques , Fibroblasts/metabolism , Granulocyte Colony-Stimulating Factor/genetics , Granulocyte Colony-Stimulating Factor/metabolism , Hematopoietic Stem Cells/drug effects , Humans , Interleukin-3/genetics , Interleukin-3/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Methylcellulose , Mice , Nerve Growth Factors/genetics , Nerve Growth Factors/metabolism , Recombinant Proteins/metabolism , Stem Cell Factor/genetics , Stem Cell Factor/metabolismABSTRACT
BACKGROUND: In acute myocardial infarction patients who do not reperfuse their infarct arteries shortly after thrombolytic treatment have a high morbidity and mortality. Management of this high risk group remains problematic, especially in centres without access to interventional cardiology. Additional thrombolytic treatment may result in reperfusion and improved left ventricular function. METHODS: Failure of reperfusion was assessed non-invasively as less than 25% reduction of ST elevation in the electrocardiographic lead with maximum ST shift on a pretreatment electrocardiogram. 37 patients with acute myocardial infarction who showed electrocardiographic evidence of failed reperfusion 30 minutes after 1.5 MU streptokinase over 60 minutes were randomly allocated to receive either alteplase (tissue type plasminogen activator (rt-PA) 100 mg over three hours) (19 patients) or placebo (18 patients). 43 patients with electrocardiographic evidence of reperfusion after streptokinase acted as controls. Outcome was assessed from the Selvester Q wave score of a predischarge electrocardiogram and a nuclear gated scan for left ventricular ejection fraction 4-6 weeks after discharge. RESULTS: Among patients in whom ST segment elevation was not reduced after streptokinase, alteplase treatment resulted in a significantly smaller electrocardiographic infarct size (14% (8%) v 20% (9%), P = 0.03) and improved left ventricular ejection fraction (44 (10%) v 34% (16%), P = 0.04) compared with placebo. This benefit was confined to patients who failed fibrinogenolysis after streptokinase (fibrinogen > 1 g/l). In patients in whom ST segment elevation was reduced after streptokinase, infarct size and left ventricular ejection fraction were not significantly different from those in patients treated with additional alteplase. CONCLUSION: Patients without electrocardiographic evidence of reperfusion after streptokinase may benefit from further thrombolysis with alteplase.
Subject(s)
Fibrinolytic Agents/therapeutic use , Myocardial Infarction/drug therapy , Streptokinase/therapeutic use , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/therapeutic use , Drug Therapy, Combination , Electrocardiography , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/physiopathology , Prospective Studies , Radionuclide Imaging , Stroke Volume , Treatment OutcomeABSTRACT
BACKGROUND: Patients who have coronary artery surgery normally occupy intensive care beds for less than 24 hours. Longer stays may result in under use of cardiac surgical capacity. One approach to optimise surgical throughput is prospectively to identify fast track patients--that is, those who occupy an intensive care bed for less than 24 hours. A prospective audit of patients was performed to identify fast track patients by simple clinical criteria. Total length of hospital stay was also assessed in an attempt to predict which patients were likely to have a short postoperative stay, defined as < or = 7 days. METHODS: Baseline demographic details, cardiovascular risk factors, angiographic and operative details were recorded for 431 consecutive patients who underwent coronary surgery at a regional centre over a nine month period. Outcome measures were the duration of the stay in the intensive care unit in hours and total duration of the postoperative stay in hospital in days. In addition, two groups of patients who were thought to be fast track were identified prospectively. Fast track 1 patients were identified by criteria selected by cardiovascular physicians. These were age less than 60 years, stable angina, good left ventricular function (ejection fraction > 50%), good renal function (serum creatinine < 120 mumol/l), and no obesity, diabetes, or other serious disease. Fast track 2 patients were identified by criteria defined by cardiovascular surgeons. These were male sex, age less than 65 years, good left ventricular function and no peripheral vascular disease, diabetes, or other serious disease. The efficacy of both sets of criteria in predicting outcome was tested. RESULTS: 344 (79.8%) patients were fast track. Significant factors for the prediction of fast track patients by univariate analysis (with positive predictive accuracy and sensitivity) were left ventricular ejection fraction > 50% (83%, 80%), left ventricular end diastolic pressure < 13 mm Hg (90%, 59%), creatinine less than 120 mumol/l (83%, 87%), and one or two vessel coronary disease (89%, 34%). Of the patients categorised as fast track 1 89% proved to be fast track (sensitivity 24%), however, the fast track 2 characteristics were not significant. Age, sex, obesity, diabetes, hypertension, a history of obstructive pulmonary disease and unstable angina were not predictive of the duration of intensive care stay. Multivariate analysis indicated that only left ventricular end diastolic pressure and the number of diseased coronary arteries predicted fast track patients. These criteria separated patients into three groups. Those who were good risk had one or two vessel disease and left ventricular end diastolic pressure < 13 mm Hg. They comprised 19% of the total and 93% of them were fast track. Those who were intermediate risk had either three vessel disease or left ventricular end diastolic pressure > 13 mm Hg but not both. They comprised 49% of the total and 85% of them were fast track. Those who were poor risk had both three vessel disease and left ventricular end diastolic pressure > 13 mm Hg. They comprised 32% of the total and 62% of them were fast track. The 106 (24%) patients who spent < or = 7 days in hospital after surgery were significantly younger (mean (SD) 55(8) v 58(8) years; P < 0.001) with a lower incidence of previous myocardial infarction (positive predictive accuracy 30%, sensitivity 53%), were less likely to have a history of obstructive pulmonary disease (25%, 98%), and more likely to have one or two vessel coronary disease (33%, 41%). They were more likely to have an internal mammary artery as a bypass conduit (27%, 89%) and more likely to need fewer than three distal anastomoses of the vein graft (29%, 63%). By multivariate analysis only age was significantly predictive of hospital stay. Total hospital stay could not be satisfactorily modelled on the basis of the criteria tested here. Sex, obesity, diabetes, hypertension, unstable angina, renal function, and left ventricular function were not associated with hospital stay. CONCLUSIONS-Most patients who had coronary artery surgery spent less than or equal to 24 hours in intensive care, but most spent > 7 days in hospital. The chance of a patient spending less than or equal to 24 hours in intensive care could be predicted by the number of coronary arteries diseased and the left ventricular end diastolic pressure. Poor risks patients (32%) had only a 62% chance of an intensive care unit stay of less than or equal to 24 hours. A policy of scheduling no more than one such patient for surgery per day would be simple to institute and would maximise the use of surgical capacity.
Subject(s)
Coronary Artery Bypass , Coronary Care Units , Length of Stay , Medical Audit , Coronary Disease/pathology , Coronary Disease/physiopathology , Coronary Vessels/pathology , Diastole , Female , Humans , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Risk Factors , Ventricular PressureABSTRACT
Class I homeobox (Hox) genes encode a major group of transcription factors controlling embryonic development and have been implicated in the continuing process of hematopoietic cell differentiation. They are clustered on four chromosomes and, in early development, exhibit spatially restricted expression with respect to their 3'-->5' chromosomal position. By using an improved PCR-based method for amplifying total cDNA derived from limited cell numbers, we now describe the expression of class I Hox genes in highly purified CD34+ cell subpopulations isolated from normal human bone marrow that represent functionally distinct stem and progenitor cell compartments. Our data indicate that at least 16 different Hox genes, mainly from the A and the B clusters, are expressed in one or more of these subpopulations of human hematopoietic cells. Moreover, markedly elevated expression of some of the Hox genes found at the 3' end of the A and B clusters (e.g., HoxB3) was a unique feature of the subpopulations that contained the most primitive functionally defined cells, whereas genes located in the 5' region of each cluster (e.g., HoxA10) were found to be expressed at nearly equal levels in the CD34+ subpopulations analyzed. In contrast to the findings for CD34+ cells, expression of two selected Hox genes, HoxB3 and HoxA10, was virtually extinguished in the CD34- fraction of bone marrow cells. These results demonstrate the expression of a broad range of Hox genes in primitive hematopoietic cells and point to the existence of a regulated program of Hox gene expression during their normal development.
Subject(s)
Antigens, CD , Bone Marrow/metabolism , Gene Expression , Genes, Homeobox , Hematopoietic Stem Cells/metabolism , Antigens, CD/analysis , Antigens, CD34 , Base Sequence , Bone Marrow Cells , Cell Division , Colony-Forming Units Assay , DNA Primers , DNA, Complementary , Flow Cytometry , Gene Expression Regulation , Hematopoietic Stem Cells/cytology , Humans , Molecular Sequence Data , Multigene Family , Polymerase Chain ReactionABSTRACT
A 62-year-old lady who was receiving corticosteroids for rheumatoid arthritis was admitted suffering from dehydration due to salmonella enteritis. Despite rehydration and appropriate chemotherapy she remained unwell and developed hypotension and elevation of her jugular venous pressure. Echocardiography and subsequent aspiration demonstrated a purulent pericardial effusion from which S typhimurium was cultured. Following aspiration and a change of antibiotic therapy, her condition improved dramatically.
Subject(s)
Enteritis/complications , Pericardial Effusion/etiology , Salmonella Infections/complications , Female , Humans , Middle Aged , Salmonella typhimurium/isolation & purificationABSTRACT
In-hospital delays to thrombolysis were significantly shorter when thrombolysis was available on admission to the accident and emergency department than after transfer to the coronary care unit (median 60 min v 84 min, p < 0.0001). With direct admission by general practitioners to a coronary care unit the subsequent in-hospital delay was shorter (median 39 min p = 0.0004), but overall delay to thrombolysis longer (median 220 v 170 min, p = 0.0019) because of longer pre-hospital delays. Overall delay was shortest with emergency ambulance referral and thrombolysis being administered in the accident and emergency department.
Subject(s)
Myocardial Infarction/drug therapy , Thrombolytic Therapy , Aged , Female , Humans , Male , Middle Aged , Time FactorsABSTRACT
The total number of clonogenic cells present in 5-week-old long-term cultures (LTC) initiated by seeding normal human marrow cells on competent adherent cell feeder layers allows for the quantitation of a more primitive hematopoietic input precursor cell type referred to as an LTC-initiating cell (LTC-IC). Previous studies have suggested that LTC-IC also circulate because production of clonogenic cells continues for many weeks when cells from the light-density (< 1.077 g/mL), T-cell-depleted fraction of normal blood are maintained on irradiated, marrow-derived feeder layers in LTC medium. We now show that the number of clonogenic cells present in such reconstructed LTC after 5 weeks is linearly related to the input number of peripheral blood (PB) cells over a wide range of cell concentrations, thereby permitting the quantitation of circulating LTC-IC by limiting dilution analysis. Using this approach, we have found the concentration of LTC-IC in the circulation of normal adults to be 2.9 +/- 0.5/mL. This is approximately 75-fold lower than the concentration of circulating clonogenic cells (ie, burst-forming units-erythroid plus colony-forming units [CFU] granulocyte-macrophage plus CFU-granulocyte, erythroid, monocyte, megakaryocyte) and represents a frequency of LTC-IC relative to all nucleated cells that is approximately 100-fold lower than that measured in normal marrow aspirate samples. Characterization studies showed most circulating LTC-IC to be small (low forward light scatter and side scatter), CD34+, Rh-123dull, HLA-DR-, and 4-hydroperoxycyclophosphamide-resistant cells, with differentiative and proliferative potentialities indistinguishable from LTC-IC in normal marrow. Isolation of the light-density, T-cell-depleted, CD34+, and either HLA-DR(low) or Rh-123(dull) fraction of normal blood yielded a highly enriched population of cells that were 0.5% to 1% LTC-IC (approximately 1,500-fold enriched beyond the light-density, T-cell-depletion step), a purity comparable to the most enriched populations of human marrow LTC-IC reported to date. However, purification of PB LTC-IC on the basis of these properties did not allow them to be physically separated from a substantial proportion (> 30%) of the clonogenic cells in the same samples, in contrast to previous findings for LTC-IC and clonogenic cells in marrow. These studies show the presence in the blood of normal adults of a relatively small but readily detectable population of functionally defined, primitive hematopoietic cells that share properties with marrow LTC-IC, a cell type thought to have in vivo reconstituting potential.(ABSTRACT TRUNCATED AT 400 WORDS)
Subject(s)
Hematopoietic Stem Cells/cytology , Adult , Antigens, CD/analysis , Antigens, CD34 , Cell Count , Cells, Cultured , Clone Cells/cytology , Erythroid Precursor Cells/cytology , Fluorescent Dyes , Granulocytes/cytology , HLA-DR Antigens/analysis , Hematopoietic Stem Cells/immunology , Humans , Immunophenotyping , Macrophages/cytology , Megakaryocytes/cytology , Monocytes/cytology , Rhodamine 123 , Rhodamines/metabolismABSTRACT
In this report we describe a quantitative in vitro assay for the most primitive type of leukemic precursors yet defined in patients with chronic myeloid leukemia (CML). This assay is based on the recently described "long-term culture-initiating cell" (LTC-IC) assay for primitive normal human hematopoietic cells. Such cells, when cocultured with competent fibroblast feeder layers, give rise after a minimum of 5 weeks to multiple single and multilineage clonogenic progenitors detectable in secondary semisolid assay cultures. Similar cultures initiated by seeding a highly enriched source of leukemic cells from patients onto normal feeders showed the clonogenic cell output after 5 weeks to be linearly related to the input innoculum over a wide range down to limiting numbers of input cells, thus allowing absolute frequencies of leukemic LTC-ICs to be determined using standard limiting dilution analysis techniques. Leukemic LTC-IC concentrations in CML marrow were found to be decreased, on average to less than 10% of the normal LTC-IC concentration in normal marrow, but were greatly increased (up to greater than 10(5) times) in CML blood. Assessment of the number of clonogenic cells produced per leukemic LTC-IC by comparison to normal blood or marrow LTC-IC values showed this function to be unchanged in leukemic LTC-ICs [i.e., 3.1 +/- 0.4 clonogenic cells per CML LTC-IC (mean +/- SEM, n = 6) versus 3.7 +/- 1.2 (n = 3) and 4.3 +/- 0.4 (n = 5), respectively, for normal blood and marrow LTC-ICs]. In contrast, leukemic LTC-IC maintenance in LTC proved to be highly defective by comparison to normal LTC-IC of either blood or marrow origin. Thus, when cells from primary LTC were subcultured into secondary LTC-IC assays, leukemic LTC-IC rapidly declined (greater than 30-fold) within the first 10 days of culture, whereas normal LTC-IC numbers remained unchanged during this period. These findings illustrate how self-maintenance and differentiation events in primitive human hematopoietic cells can be differentially modulated by an oncogenic process and provide a framework for further studies of their manipulation, analysis, and therapeutic exploitation.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Neoplastic Stem Cells/pathology , Bone Marrow/pathology , Cell Division , Hematopoietic Stem Cells/pathology , Humans , In Vitro Techniques , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood , Time Factors , Tumor Cells, Cultured/pathologyABSTRACT
The aim of this study was to assess whether the incidence of early occlusion following angioplasty was greater among patients with unstable angina and whether the coronary lesions prone to early occlusion could be predicted from their angiographic appearance. Seventy-seven patients who had had a first angioplasty of a native vessel for stable or unstable angina in one twelve month period were included. The angiographic appearances of the angioplastied lesions were classified as either Type 1, which were smooth and unlikely to have thrombus or intimal rupture, or Type 2, which were irregular due to thrombus or intimal rupture. The lesion classification was compared to the patients' clinical features, i.e. stable or unstable angina, and the outcome of the angioplasty. Type 2 lesions occurred in 25% of patients with stable angina but 49% of patients with unstable angina (p less than 0.05). Early sudden occlusion of the angioplastied vessel occurred in 24% of patients with unstable angina but in only 3% of patients with stable angina (p less than 0.05) and in 6% of Type 1 lesions compared with 24% of Type 2 lesions (p less than 0.05). Thus it is possible to identify the clinical characteristics and angiographic appearances of those patients undergoing angioplasty who are most likely to experience early vessel occlusion.
Subject(s)
Angioplasty, Balloon, Coronary , Coronary Disease/epidemiology , Angina Pectoris/complications , Angina Pectoris/diagnostic imaging , Angina Pectoris/therapy , Angina, Unstable/complications , Angina, Unstable/diagnostic imaging , Angina, Unstable/therapy , Angioplasty, Balloon, Coronary/adverse effects , Chi-Square Distribution , Coronary Angiography , Coronary Disease/diagnostic imaging , Coronary Disease/pathology , Coronary Disease/therapy , Humans , Incidence , Prognosis , Recurrence , Reproducibility of ResultsABSTRACT
A 24 year old patient presented with incessant atrial tachycardia during the course of a twin pregnancy. Medical treatment slowed the ventricular response without restoring sinus rhythm. During labour the tachycardia spontaneously reverted to sinus rhythm. Subsequently the same arrhythmia was documented with a slower ventricular response than during pregnancy.
Subject(s)
Pregnancy Complications, Cardiovascular/physiopathology , Pregnancy, Multiple/physiology , Tachycardia, Supraventricular/physiopathology , Adult , Electrocardiography , Female , Humans , Labor, Obstetric/physiology , Pregnancy , TwinsABSTRACT
Despite numerous publications, mostly with small patient populations, the management of post-infarct septal rupture is still not well defined. Although urgent surgery appears to be the therapy of choice it is still unclear whether surgery very early after septal rupture in patients with severe haemodynamic compromise salvages a significant number of patients. In this paper we present the data from a large population of consecutive patients with post-infarct septal rupture from one cardiac centre. From 1980 through 1989, 108 patients with post-infarct septal rupture were seen at this Regional centre of whom 81 had operative repair; 43 (53%) of these survived the early postoperative period. Of 32 patients with cardiogenic shock who had surgery, early operative mortality in those operated on within 48 h of rupture was 90% (18/20) compared with 33% (4/12) in those operated on later (P less than 0.001). All survivors with pre-operative shock had intra-aortic balloon counter-pulsation before operation. Concomitant coronary artery bypass grafting was not associated with improved survival in our patients. Three patients survived long-term without operation. Analysis of population statistics suggest that approximately 270 patients with post-infarction septal rupture were not transferred from peripheral hospitals to the Regional Cardiothoracic Centre for assessment during this decade.