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Biomedical subjects

J Slater

Publications and source records attributed to J Slater.

At least 19 recordsLinked to original sources

An observational study of practice during transfer of patients from anaesthetic room to operating theatre.

We observed practice during transfer of 80 patients from anaesthetic room to operating theatre, to determine the duration of apnoea and the time without monitoring during the transfer process. Median (IQR [range]) time from disconnection of the breathing system in the anaesthetic room to the first breath in theatre was 54 (44-65 [27-196]) s, and from disconnection of the pulse oximetry probe to the first reading in theatre was 90 (74-103 [44-182]) s. In four patients (5%) arterial oxygen saturation fell to 94%, with the greatest desaturation observed 11%. The transfer process may represent a window of opportunity for the occurrence of harm or the first step in a chain of events leading to harm, and is difficult to justify on patient safety grounds.

Adult↗

Association between air pollution exposure and exhaled nitric oxide in an elderly population.

BACKGROUND: Animal models suggest that the cardiovascular effects of air pollution result in part from inflammation caused by proinflammatory mediators originating in the lung. In a human study of the cardiovascular effects of air pollution, we aimed to evaluate the potential association between air pollution levels and the fraction of exhaled nitric oxide (FE(NO)), a non-invasive measure of airway inflammation. METHODS: Breath samples were collected weekly between September and December 2000 in a community based group of elderly subjects (median age 70.7 years) in Steubenville, Ohio. The samples were analysed for NO. Air pollution levels were measured concurrently at a central site monitor. RESULTS: An increase in the 24 hour average PM(2.5) concentration of 17.7 micro g/m(3) was associated with an increase in FE(NO) of 1.45 ppb (95% CI 0.33 to 2.57) in models adjusted for subject, week of study, day of the week, hour of the day, ambient barometric pressure, temperature, and relative humidity. This represents a change of approximately 15% compared with the mean FE(NO) in the cohort (9.9 ppb). A significant association was also observed for a 24 hour moving average of ambient NO (0.83 ppb increase, 95% CI 0.26 to 1.40). In two-pollutant models, the magnitude and precision of the PM(2.5) effect was not reduced and the ambient NO effect was no longer significant. The associations between FE(NO) and PM(2.5) were significantly higher in subjects with a doctor's diagnosis of COPD (p value for interaction = 0.03). CONCLUSIONS: Ambient pollution may lead to airway inflammation as measured by FE(NO). These subclinical inflammatory changes may be an important step in the pathogenesis of the cardiopulmonary effects induced by exposure to air pollution.

Aged↗

Testicular germ cell tumour presenting as thyrotoxicosis.

A case is reported of a patient who presented to his family doctor with a short history of cough with signs and symptoms of thyrotoxicosis. Carbimazole treatment had little effect and his symptoms worsened to include severe shortness of breath. He was investigated further and found to have multiple lung and liver metastases from an unknown primary site. Biopsy and subsequent post-mortem investigations revealed a testicular tumour and a grossly elevated serum human chorionic gonadotrophin (hCG) concentration. The biochemical and clinical thyrotoxicosis is presumed to be due to the thyrotrophic activity of excess hCG secretion, in a situation analogous to that seen in hydatidiform mole or in hyperemesis gravidarum.

Antithyroid Agents↗

Early revascularization is associated with improved survival in elderly patients with acute myocardial infarction complicated by cardiogenic shock: a report from the SHOCK Trial Registry.

AIMS: The SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK (SHOCK) Trial showed no benefit of early revascularization in patients aged >/=75 years with acute myocardial infarction and cardiogenic shock. We examined the effect of age on treatment and outcomes of patients with cardiogenic shock in the SHOCK Trial Registry. METHODS AND RESULTS: We compared clinical and treatment factors in patients in the SHOCK Trial Registry with shock due to pump failure aged <75 years (n=588) and >/=75 years (n=277), and 30-day mortality of patients treated with early revascularization <18 hours since onset of shock and those undergoing a later or no revascularization procedure. After excluding early deaths covariate-adjusted relative risk and 95% confidence intervals were calculated to compare the revascularization strategies within the two age groups. Older patients more often had prior myocardial infarction, congestive heart failure, renal insufficiency, other comorbidities, and severe coronary anatomy. In-hospital mortality in the early vs. late or no revascularization groups was 45 vs. 61% for patients aged <75 years (p=0.002) and 48 vs. 81% for those aged >/=75 years (p=0.0003). After exclusion of 65 early deaths and covariate adjustment, the relative risk was 0.76 (0.59, 0.99; p=0.045) in patients aged <75 years and 0.46 (0.28, 0.75; p=0.002) in patients aged >/=75 years. CONCLUSIONS: Elderly patients with myocardial infarction complicated by cardiogenic shock are less likely to be treated with invasive therapies than younger patients with shock. Covariate-adjusted modeling reveals that elderly patients selected for early revascularization have a lower mortality rate than those receiving a revascularization procedure later or never.

Aged↗

Solving inequities in provider distribution: loan repayment.

The distribution of primary health care professionals in England and Wales is inequitable, with relatively lower concentrations of professionals in deprived areas. The objective of the present study was to determine whether graduate health professionals would be willing to work in under-served areas in return for educational loan repayment. The study group consisted of a convenience sample of 50 newly qualified and trainee general practitioners, and 50 newly qualified community nurses and health visitors in mid- and west Wales. At interview, the subjects were presented with descriptions of general practices and asked to indicate their preferred practice. Practice descriptions varied systematically in terms of location (i.e. urban, suburban and rural), population deprivation (i.e. deprived or mixed affluent/deprived) and availability of loan repayment (i.e. none or loans paid off over a period of between one and 4 years). The main outcome was the probability that a practice with loan repayment was chosen. Compared with a suburban practice, a one-year loan repayment option made the rural and urban deprived practices 1.6 times and 1.2 times more likely to be chosen, respectively. Nurses were generally more willing than doctors to work in a deprived area in return for loan repayment. The findings suggest that loan repayment may offset health professionals' aversion to working in deprived areas. Such a scheme needs to be piloted to see whether it does offer value for money in recruiting health professionals to under-served areas.

Adult↗

Changes in the practice of percutaneous coronary intervention: a comparison of enrollment waves in the National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry.

The National Heart, Lung, and Blood Institute Dynamic Registry includes 15 clinical sites in wave 1, and 16 sites in wave 2 as well as a data-coordinating center. The first wave of enrollment began in July 1997 and was completed in February 1998. The second wave began in February 1999 and ended in June 1999. There were a total of 2,526 patients in wave 1 and 2,109 patients in wave 2. Comprehensive pre-, intra-, and postprocedure (in-hospital) data were analyzed for changes between recruitment waves. Patients in wave 2 were more frequently nonwhite (p < or = 0.001), hypertensive by history (p < or = 0.001), had more significant noncardiac comorbidity (p < or = 0.01), and had more frequently undergone prior percutaneous coronary intervention (p < 0.05). Patients in wave 2 underwent percutaneous coronary intervention in a setting of acute coronary syndromes more frequently than wave 1 patients (p < or = 0.001). However, most interventions in both waves were performed on 1 vessel, irrespective of the extent of disease. Attempted lesions in wave 2 were longer (p < or = 0.001), less frequently totally occluded (p < or = 0.001), and more frequently in vessels with a prior stent (p < or = 0.01). Using the American Heart Association/American College of Cardiology lesion classification scheme, attempted lesions in wave 2 were less complex than those in wave 1 (p < or = 0.001). Stent use increased significantly from wave 1 (67%) to wave 2 (79%, p < or = 0.001) as did the use of platelet glycoprotein IIb/IIIa antagonists (wave 1, 24%; wave 2, 32%: p < 0.001). Procedural outcomes (angiographic success without major in-hospital adverse events) were excellent in both waves 1 (94.6%) and 2 (95.6%) and were not significantly different. However, the frequency of significant procedural coronary dissection and in- and out-of-laboratory abrupt closure were significantly less in wave 2 (p < or = 0.001) Discharge medications were more likely to include angiotensin-converting enzyme inhibitors, beta-adrenergic blocking agents, and hypolipidemic treatment in wave 2 than in wave 1 (p < or = 0.001). These data indicate a continuing aggressive approach to patient care over the time interval analyzed. Although overall procedural outcomes are excellent, procedural safety has been further enhanced. There is also a growing awareness of the importance of secondary prevention among interventional cardiologists.

Aged↗

Use of an electronic medical record in disease management programs: a case study in hyperlipidemia.

Disease management programs seek to improve the health of a population of patients with a disease through a multidisciplinary approach founded in the collection, analysis and feedback of disease-specific outcomes. Currently, the majority of disease management programs have been conducted by insurers or external vendors. Limitations of these programs derive from separation of care from primary care and the inability to rapidly and accurately obtain the necessary clinical data. The utility offered by an electronic medical record allows physician organizations to conduct disease management programs of higher quality at lower cost.

Coronary Disease↗

Percutaneous coronary intervention in the current era compared with 1985-1986: the National Heart, Lung, and Blood Institute Registries.

BACKGROUND: Although refinements have occurred in coronary angioplasty over the past decade, little is known about whether these changes have affected outcomes. METHODS AND RESULTS: Baseline features and in-hospital and 1-year outcomes of 1559 consecutive patients in the 1997-1998 Dynamic Registry who were having first coronary intervention were compared with 2431 patients in the 1985-1986 National Heart, Lung, and Blood Institute Registry. Compared with patients in the 1985-1986 Registry, Dynamic Registry patients were older (mean age, 62 versus 58 years; P:<0.001) and more often female (32.1% versus 25.5%; P:<0.001). In the Dynamic Registry, procedures were more often performed for acute myocardial infarction (22.9% versus 9.9%; P:<0.001) and treated lesions were more severe (84.5% versus 82.5% diameter reduction; P:<0.001), thrombotic (22.1% versus 11.3%; P:<0.001) or calcified (29.5% versus 10.8%; P:<0.001). Stents were used in 70.5% of Dynamic Registry patients, whereas 1985-1986 patients received balloon angioplasty alone. Procedural success was higher in the Dynamic Registry (92.0% versus 81.8%; P:<0.001) and the rate of in-hospital death, myocardial infarction, and emergency coronary bypass surgery combined was lower (4.9% versus 7.9%; P:=0.001) than in the 1985-1986 Registry. The 1-year rate for CABG was lower in the Dynamic Registry (6.9% versus 12.6%; P:<0.001). CONCLUSIONS: Although Dynamic Registry patients had more unstable and complex coronary disease than those in the 1985-1986 Registry, their rate of procedural success was higher whereas rates of complications and subsequent CABG were lower. Results of percutaneous coronary intervention have improved substantially over the past decade.

Angioplasty, Balloon, Coronary↗

Centripetal versus centrifugal bias in visual line bisection: focusing attention on two hypotheses.

A variety of stimulus factors have been shown to influence the degree of leftward displacement of perceived line midpoint (i.e., pseudoneglect), which typifies the performance of normal subjects in line bisection tasks [M.E. McCourt & G. Jewell: Neuropsychologia 37, 843-855 (1999); G. Jewell & M.E. McCourt: Neuropsychologia 38, 93-110 (2000)]. One such factor is the position of lines within the visual field, where two conflicting patterns of bisection error have been reported. Some authors report a centrifugal pattern of error, where perceived line midpoint shifts away from the vertical midline, regardless of line position, i.e., relatively leftward for leftward displaced lines and vice versa. Others have reported a centripetal pattern of bisection error, where perceived line midpoint is always displaced centrally, toward the vertical midline, regardless of line position. There is no satisfactory explanation for these discrepant findings. An experiment using a tachistoscopic forced-choice line bisection protocol is described which discloses that neurologically normal right-handed subjects (N=82) typically display a centrifugal pattern of bisection error when lines are azimuthally displaced over a relatively small range, whereas a centripetal pattern is observed when lines are displaced over a wider range. Results from ancillary control experiments, in which eye position was measured during testing, confirm that systematic differences in gaze direction do not occur as a function of line position, and thus cannot account for the different patterns of bisection error. We conclude that stimulus context significantly modulates the strategy with which observers deploy spatial attention. When line position is constant, or varies over a narrow range, observers hold attention steady and widen its aperture to accommodate the relevant range of spatial location. Centrifugal bisection error is thus produced by the asymmetric cueing effect of laterally displaced lines, according to the activation-orientation theory [M. Kinsbourne: Acta Psychologica 33, 193-201 (1970)]. When the range of line position exceeds the aperture of focal attention, we hypothesize that observers adopt a strategy in which attention is dynamically scanned in the direction of azimuthally displaced lines. The effects of attentional scanning on line bisection performance are quite robust. The centripetal scanning proposed to occur for widely displaced lines is consistent with the centripetal pattern of bisection error in this condition.

Adult↗

Cardiogenic shock due to cardiac free-wall rupture or tamponade after acute myocardial infarction: a report from the SHOCK Trial Registry. Should we emergently revascularize occluded coronaries for cardiogenic shock?

OBJECTIVES: We sought to compare the characteristics and outcomes of patients with acute myocardial infarction (MI) and cardiogenic shock (CS) caused by rupture of the ventricular free wall or tamponade versus shock from other causes. BACKGROUND: Free-wall rupture is a recognized cause of mortality in patients with acute MI. Some of these patients present subacutely, which provides an opportunity for intervention. Recognition of factors that distinguish them from the overall shock cohort would be beneficial. METHODS: The international SHOCK Trial Registry enrolled patients concurrently with the randomized SHOCK Trial. Thirty-six centers consecutively enrolled all patients with suspected CS after MI, regardless of trial eligibility. RESULTS: Of the 1,048 patients studied, 28 (2.7%) had free-wall rupture or tamponade. These patients had less pulmonary edema, less diabetes, less prior MI, and less prior congestive heart failure (all p < 0.05). They more often had new Q waves in two or more leads (51.9% vs. 31.5%, p < 0.04), but MI location and time to shock onset after MI did not differ. Of patients with rupture or tamponade, 75% had pericardial effusions. No hemodynamic characteristics identified patients with rupture/tamponade. Most patients with rupture/tamponade had surgery and/or pericardiocentesis (27/28); their in-hospital survival rate was identical to that of the group overall (39.3%). Women and older patients with rupture/tamponade tended to survive intervention less often. CONCLUSIONS: Free-wall rupture and tamponade may present as CS after MI, and survival after intervention is similar to that of the overall shock cohort. All patients with CS after MI should have echocardiography in order to detect subacute rupture or tamponade and initiate appropriate interventions.

Aged↗

Cost effectiveness analysis of school based Mantoux screening for TB infection.

OBJECTIVE: To assess the cost-effectiveness of adding school based Mantoux screening programs to the New South Wales current TB prevention strategy. METHOD: A decision analysis model compared the costs and consequences of screening strategies against the current no-screen strategy. Costs associated with screening and with treating future cases of TB were considered. Consequences considered were deaths and adult cases of TB prevented. The study was based on data from prevalence surveys conducted in 1992 and 1994 in Central and South Western Sydney, New South Wales. Screening strategies considered were screening all or only overseas born (OSB) 6 year olds and all or only OSB 14 year olds in school settings. RESULTS: Screening 14 year olds prevented more deaths and adult cases of TB than screening 6 year olds for a similar cost. For both age groups targeted screening of OSB children was more cost-effective than screening all children. Targeted screening of 14 year olds--the most cost effective option--cost $17,956 (costs and benefits discounted at 5%) per adult case prevented, equivalent to approximately $130,000 per life year saved. The cost-effectiveness ratios decline substantially if lower discount rates and less conservative assumptions are applied. CONCLUSION: Targeted screening was more cost effective than screening all children, however, there are ethical implications of targeting a group based on their origin of birth. IMPLICATIONS: As prevention and control of TB continues to be a high priority for NSW, the implications of a school based screening program should be seriously considered.

Adolescent↗

Skin prick test reactivity to recombinant latex allergens.

BACKGROUND: Allergy to latex has become a serious and increasingly common health problem, particularly for healthcare workers and patients who undergo frequent surgical procedures. Testing for latex allergy currently involves in vitro tests and skin prick testing using crude preparations of natural rubber latex (NRL). To date, 10 latex proteins have received designation as allergens (Hev b 1 to Hev b 10) and, except for Hev b 4, have been cloned as recombinant proteins. Our aim was to compare the skin prick test (SPT) reactivity of six recombinant latex allergens with SPT reactivity to natural rubber latex proteins in known latex-allergic individuals. METHODS: Six recombinant proteins were expressed in Escherichia coli, and tested as the intact fusion proteins (Hev b 2, 5, 6, 8) or as purified proteins (Hev b 3 and 7). SPT with the six recombinant latex allergens was performed using 10-fold serial dilutions on 31 latex-allergic subjects to determine the level of reactivity to each recombinant allergen. Latex-specific IgE was determined using the AlaSTAT assay. RESULTS: All six recombinant allergens were reactive by SPT in at least 1 latex-allergic patient but not in any of the control patients. The frequency of sensitization to the various recombinant allergens was similar to previous studies using the native proteins isolated from NRL. The minimal level of protein for a positive skin test was 70 pg/ml for NRL and 1 ng/ml for one recombinant allergen (Hev b 7). In our patients, the use of a combination of recombinant latex allergens Hev b 5, 6 and 7 diagnosed latex allergy with 93% sensitivity and 100% specificity. CONCLUSION: Recombinant latex allergens are clinically reactive, can be produced in a standardized manner, and could potentially provide safe, sensitive and specific reagents for the diagnosis of latex allergy.

Adult↗

Equine immunity to viruses.

The identification of some of the adaptive immune responses to infection with equine viruses has been the first step toward rational immunoprophylactic design. Sufficient knowledge of infection-induced immunity and informed estimates of the requirements for long-term immunity for EIV have now been obtained. Thus, the future for inactivated EIV vaccines is promising now that new adjuvants have been applied to induce cellular immunity and safe methods have been designed to stimulate virus-neutralizing (VN) antibody at mucosal surfaces. Adenoviruses induce circulating VN antibody, the presence of which appears to correlate with protection from reinfection. Therefore, the potential of vaccines to induce VN antibody and protect from challenge is an important next step with this virus. With persistent viruses such as EHV-1, antibody-mediated protection from infection can be achieved only at the site of initial infection, that is, the nasopharynx and upper respiratory tract. Systemic dissemination is very rapid and consequently VN antibody is unlikely to play a major role in prevention of disease once the initial infection event has occurred. Cellular immune responses, particularly CTLs, play a dominant role in protection and recovery and are important in immune surveillance and determination of the outcome of reactivation of latent virus. Therefore, the key to future EHV-1 vaccine design is to focus on stimulation of CTL responses, and this requires the successful presentation of vaccine-derived antigenic peptides to MHC class I molecules that are recognized by specific receptors on CTL. There is some evidence that stimulation of EHV-1-specific CTL precursors may correlate with immunity to this virus. By analogy with gamma herpesviruses in humans, CTL precursor frequency may also function as an immune correlate for EHV-2. Although EAV infection induces strong immunity in females and geldings, persistent infection of the genital tract is an important route of dissemination from stallions. Although inactivated vaccines induce strong immunity (which depends upon VN activity of serum antibody) to first infection, the immunologic control of persistent infection is currently poorly understood; however, analogy with other persistent viruses suggests that CTLs are also likely to play an important role in the control of persistent EAV infections.

Acute-Phase Proteins↗

Stimulus dependence of the development of the zebrafish (Danio rerio) vestibular system.

It has been suggested that stimulus dependence is a general feature of all developing sensory systems. We tested this idea for the developing zebrafish vestibular system using a bioreactor the National Aeronautic and Space Agency designed to simulate microgravity for cells in culture on earth. We replaced the culture medium with aquarium water and maintained zebrafish eggs/hatchlings in the bioreactor for either 72 or 96 h postfertilization. These experimental animals displayed a swimming behavior that was indistinguishable from the control animals when illuminated from above. However, when illuminated from below, experimental animals swam not only dorsal surface up, but also lying on their side; they corkscrewed, swam vertical loops, and occasionally even swam upside down. When incubated in the bioreactor for 96 h, the saccular otolith was significantly smaller than normal, suggesting that otolith development was either delayed or slower than normal. When incubated in the bioreactor for 72 h, some animals were missing one or more otoliths. In contrast, control animals all had two otoliths on each side. This supports the idea that otolith development was delayed. Immediately upon removal from the bioreactor at 96 h, experimental animals showed some signs of compensatory eye rotation, but with a much less clear relationship between the orientation of the eye and the direction of gravity than the age-matched control animals. This difference was still obvious 1 day later. These results support the idea that development of the vestibular system in zebrafish is dependent on the presence of the normal stimulus the system is designed to detect.

Animals↗

Access to coronary artery bypass surgery by race/ethnicity and gender among patients who are appropriate for surgery.

OBJECTIVE: The study sought to determine if there were race/ethnicity or gender differences in access to coronary artery bypass graft (CABG) surgery among patients who have been designated as appropriate and as necessary for that surgery according to the RAND methodology. METHODS: RAND appropriateness and necessity criteria were used to identify a race/gender stratified sample of postangiography patients who would benefit from coronary artery bypass graft surgery. These patients were tracked for 3 months to determine if they had undergone coronary artery bypass graft surgery in New York State. Subjects were a total of 1,261 postangiography patients in eight New York hospitals in 1994 to 1996. Measures included percentages of patients for whom coronary artery bypass graft surgery was appropriate and necessary undergoing surgery by race/ethnicity and gender, as well as multivariate odds ratios for race/ethnicity and gender. RESULTS: After controlling for age, payer, number of vessels diseased, and presence of left main disease, African-American and Hispanic patients were found to be significantly less likely to undergo coronary artery bypass graft surgery than white non-Hispanic patients (respective odds ratios 0.64 and 0.60). When "necessity" was used as a criterion instead of "appropriateness," significant differences in access for African-American patients remained. The gatekeeper physician recommended surgery only 10% of the time that patients did not undergo "appropriate" coronary artery bypass graft surgery, and this percentage did not vary significantly by race/ethnicity or gender of the patient. CONCLUSIONS: Even after controlling for appropriateness and necessity for coronary artery bypass graft surgery in a prospective study, African-American patients had significant access problems in obtaining coronary artery bypass graft surgery. These problems appeared not to be related to patient refusals.

Black or African American↗

Prolonged discordant xenograft survival and delayed xenograft rejection in a pig-to-baboon orthotopic cardiac xenograft model.

OBJECTIVE: Our objectives were to study delayed xenograft rejection and the effectiveness of pretransplantation total lymphoid irradiation combined with immunosuppression on rejection in a pig-to-baboon cardiac xenograft model. METHODS: Baboons were treated with pretransplantation total lymphoid irradiation, cyclosporine A (INN: ciclosporin), and methotrexate. Orthotopic pig-to-baboon cardiac transplantations were performed after depletion of circulating xenoreactive natural antibody by pretransplantation donor organ hemoperfusion. Tissue samples were collected for immunologic and immunopathologic evaluation. RESULTS: Pig cardiac xenografts survived more than 18 and 19 days without evidence of hyperacute rejection. Immunologic analysis of serum samples demonstrated that circulating xenoreactive natural antibody levels did not return to pretransplantation levels. The production of xenoreactive natural antibodies from the recipient's splenocytes was inhibited completely. Histologic examination of xenografts showed the feature of acute vascular rejection. Immunohistochemical studies demonstrated infiltration of cardiac xenografts by large numbers of macrophages, small numbers of natural killer cells, and a few T cells. The infiltrating macrophages also showed expression of interleukin-1 and tumor necrosis factor. Diffuse deposition of immunoglobulin G, C1Q, C3, and fibrin on xenograft vasculature was observed. Interleukin-2 expression was not found in rejected cardiac xenografts. Xenograft endothelial cells also showed evidence of activation (expression of cytokines interleukin-1 and tumor necrosis factor). CONCLUSIONS: This study demonstrates prolonged discordant cardiac xenograft survival and delayed xenograft rejection in a pig-to-baboon model. The delayed xenograft rejection is mediated by both humoral and cellular mechanisms. Pretransplantation total lymphoid irradiation combined with cyclosporine A and methotrexate can inhibit xenoreactive natural antibody production but not elicited antipig antibody production and the xenoreactivity of macrophages.

Animals↗

Homozygous deletions at 9p21 in childhood acute lymphoblastic leukemia detected by microsatellite analysis.

To gain a fuller understanding of the role of deletions of chromosome 9 in the development of childhood acute lymphoblastic leukemia (ALL), we performed detailed deletional mapping of chromosome 9 in 54 primary ALL samples with matched normal DNA using 22 highly polymorphic markers; and this information was combined with our previous data concerning the presence of deletions of CDKN2/INK4A/p16 and CDKN2B/INK4B/p15 in these samples. We have found a very high frequency of loss of heterozygosity (LOH) (31 of 54 cases (57%)) on chromosome arm 9p. As expected, the smallest region of LOH was between D9S1747 and D9S1748 at 9p21, including CDKN2/INK4A/p16, but excluding CDKN2B/INK4B/p15. Homozygous deletions at 9p21 occurred in 23 of 54 (43%) samples (seven of 11 (64%) T-ALL, 16 of 45 (36%) precursor-B ALL). We detected seven cases of homozygous deletions at 9p21 which had not been detected by Southern blot hybridization, showing the power of microsatellite analysis in detecting homozygous deletions. In most cases, homozygous deletions were limited to the region between D9S1747 and CDKN2B/INK4B/p15. We have attempted to determine the mechanism and timing of 9p deletions. Of the 23 samples with homozygous deletions at 9p21, 21 samples had surrounding large LOH. Of the 29 samples with LOH of 9p, homozygous deletion at 9p21 was identified in 22 cases. In addition, six patients have been studied at diagnosis and relapse, all six showed the same 9p21 structure at relapse (normal, three patients; hemizygous deletions, two patients; homozygous deletion, one patient) as their initial presentation. Finally, three patients (homozygous deletion, one patient; hemizygous deletion, two patients) had the IFN-alpha rather than CDKN2/INK4A/p16 deleted. In summary, these data further emphasize the importance of 9p21 loss in the development of childhood ALL.

Carrier Proteins↗