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Biomedical subjects

L Kaufman

Publications and source records attributed to L Kaufman.

At least 19 recordsLinked to original sources

Precision measurement of the neutron spin asymmetryA(n)(1) and spin-flavor decomposition in the valence quark region.

We have measured the neutron spin asymmetry A(n)(1) with high precision at three kinematics in the deep inelastic region at x=0.33, 0.47, and 0.60, and Q(2)=2.7, 3.5, and 4.8 (GeV/c)(2), respectively. Our results unambiguously show, for the first time, that A(n)(1) crosses zero around x=0.47 and becomes significantly positive at x=0.60. Combined with the world proton data, polarized quark distributions were extracted. Our results, in general, agree with relativistic constituent quark models and with perturbative quantum chromodynamics (PQCD) analyses based on the earlier data. However they deviate from PQCD predictions based on hadron helicity conservation.

Journal Article↗

Seasonality in clinical onset of type 1 diabetes in belgian patients above the age of 10 is restricted to HLA-DQ2/DQ8-negative males, which explains the male to female excess in incidence.

AIMS/HYPOTHESIS: Type 1 diabetes arises from an interplay between environmental and genetic factors. The reported seasonality at diagnosis supports the hypothesis that currently unknown external triggers play a role in the onset of the disease. We investigated whether a seasonal pattern is observed at diagnosis in Belgian Type 1 diabetic patients, and if so whether seasonality varies according to age, sex and genetic risk, all known to affect the incidence of Type 1 diabetes. METHODS: The seasonal pattern at clinical diagnosis was assessed in 2176 islet antibody-positive diabetic patients aged 0 to 39 years diagnosed between 1989 and 2000. Additional stratification was performed for age, sex and HLA-DQ genotype. RESULTS: Overall, a significant seasonal pattern at clinical diagnosis of diabetes was observed (p<0.001). More subjects were diagnosed in the period of November to February (n=829) than during the period of June to September (n=619) characterised by higher averages of maximal daily temperature and daily hours of sunshine. However, the seasonal pattern was restricted to patients diagnosed above the age of 10 (0-9 years: p=0.398; 10-19 years: p<0.001; 20-29 years: p=0.003; 30-39 years: p=0.015). Since older age at diagnosis is associated with a male to female excess and a lower prevalence of the genetic accelerator HLA-DQ2/DQ8, we further stratified the patients aged 10 to 39 years (n=1675) according to HLA-DQ genotype and sex, and we found that the seasonal pattern was largely restricted to male subjects lacking DQ2/DQ8 (n=748; p<0.00 vs all others: n=927; p=0.031). CONCLUSIONS/INTERPRETATION: In a subgroup of male patients diagnosed over the age of 10, the later stages of the subclinical disease process may be more driven by sex- and season-dependent external factors than in younger, female and genetically more susceptible subjects. These factors may explain the male to female excess in diabetes diagnosed in early adulthood.

Adolescent↗

Persistent pulmonary hypertension late after neonatal aortic valvotomy: a consequence of an expanded surgical cohort.

BACKGROUND: Survival of neonates with critical aortic stenosis has improved over the past decade. Models based on morphological characteristics have been designed to help determine whether early survival is more likely after biventricular repair (surgical or balloon aortic valvotomy) or after a single ventricle staged palliative surgical strategy. However, late follow up data are lacking. OBJECTIVE: To report follow up data on survivors of neonatal aortic valvotomy who had persistent pulmonary hypertension caused by restriction to left ventricular filling. RESULTS: Of four medium term survivors of neonatal valvotomy for critical aortic stenosis who had persistent pulmonary hypertension, one died aged 4 years and the other three have severe limitation of effort tolerance. CONCLUSIONS: This previously unreported late complication of "successful" biventricular repair for neonatal critical aortic stenosis is an important consideration in determining the initial management.

Aortic Valve Stenosis↗

Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation.

Serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF)-alpha were frequently measured during the first 30 days after allogeneic bone marrow transplantation (BMT) in 84 consecutive adult patients. Major transplant-related complications (MTCs) occurred in 33% of cases and included veno-occlusive liver disease, idiopathic pneumonia syndrome, severe endothelial leakage syndrome and >grade II acute graft-versus-host disease. Compared with patients having minor complications, those with MTCs developed higher levels at times of maximal clinical signs (all cytokines, P<0.001), between days 0-5 post-BMT (IL-6 and IL-8, P<0.05) and days 6-10 (L-6, P<0.001; IL-8 and TNF, P<0.01) post-BMT. We could not discriminate patterns of cytokine release that were specific for any subtype of MTC. Higher levels of IL-8 during days 0-5 were associated (P=0.044) with early (<40 days) death. Multivariate analysis including patient and transplant characteristics as well as post-BMT levels of C-reactive protein showed that high average levels of one or more of the cytokines within the first 10 days post-BMT were independently associated with MTC (Odd's ratio: 2.3 [1.2-4.5], P=0.011). This study shows that systemic release of proinflammatory cytokines contributes to the development of MTC and provides a rationale for pre-emptive anti-inflammatory treatment in selected patients.

Adult↗

Patterns of failure following curative resection of colorectal liver metastases.

AIMS: Several studies have focused on factors determining recurrence and survival rate after curative resection of colorectal liver metastases (LM). Data are lacking with regard to patterns of failure indicating where and when recurrences arise. METHODS: One-hundred-and-five consecutive patients [F/M: 31/74; mean age 61 years (range 36-80 y)] with primary colorectal liver metastases underwent surgical R0 curative resection between 1990-1999. Patient follow-up was closed in January 2002. The common closing date method was used for survival analysis. Multivariate analysis was performed with the Cox proportional hazard technique. RESULTS: The overall (OS) vs disease free survival (DFS) rates at 1, 2, and 5 years were 88.5 vs 63.3, 73.4 vs 40.2, and 36.8 vs 18.1%, respectively. Elevated serum CEA level was the only factor independently related to recurrent disease. Elevated serum CEA level, maximum diameter of liver metastases (LM), and satellitosis were factors significantly related to poor OS. Recurrent liver metastases developed in 43% and extra-hepatic metastases in 60% of the patients. In about half of the patients cancer recurrence was observed within 18 months, almost equally distributed between hepatic and extra-hepatic sites. CONCLUSION: Despite optimal patient selection and curative resection of colorectal liver metastases, more than a half of the patients developed cancer recurrence within 2 years.

Adult↗

Oesophageal pH monitoring in children: how is it perceived by the parents and does the technique change feeding and daily activity?

AIM: To determine whether oesophageal pH monitoring in infants induces changes in daily activity and feeding, and with the help of a questionnaire to evaluate how parents perceive pH monitoring. METHODS: The parents of 100 children, consecutively referred for oesophageal pH monitoring, were asked by one of the authors (A.A.) to respond to a standardized questionnaire immediately after the end of the procedure. Twenty questions were asked, concerning five topics: feeding (4 questions), activity (6 questions), perception of the parents (6 questions), accuracy of the provided information (3 questions), and previous experience with oesophageal pH-metry (1 question). For statistical analysis, every variable was qualified as "no change" and "change" for feeding and activity, as "positive" or "negative" regarding the perception of the test, and as "sufficient" or "insufficient" regarding the information provided. The answers to the questions were also analysed according to the result of the oesophageal pH monitoring (normal vs abnormal), and according to whether or not there was previous experience of oesophageal pH-metry in a first degree relative. RESULTS: Changes in feeding occurred in 28% of cases and changes in activity in 30%, but did not differ according to the oesophageal pH-metry result. Equally, the perception of the parents regarding the test (37% negative), the acceptability of a second pH-metry test (refusal in 52%) and previous experience with oesophageal pH-metry (positive in 25%) were not influenced by the result of the pH monitoring. Parents of infants with abnormal oesophageal pH monitoring were more frequently dissatisfied with the information about the nature of the test provided before the test and also the results than parents of infants with normal results (52% vs 19%, respectively; p < 0.05). CONCLUSION: According to the perception of the parents, pH monitoring induces changes in feeding and activity in 28% and 30%%, respectively; 63% of the parents considered pH monitoring to be well tolerated. Parents of infants with abnormal pH monitoring results need more attention.

Attitude↗

IA-2 autoantibodies predict impending type I diabetes in siblings of patients.

AIMS/HYPOTHESIS: Multiple islet autoantibody positivity is currently believed to best predict progression to Type I (insulin-dependent) diabetes mellitus. We compared its predictive value with that of positivity for a particular type of islet autoantibody, directed against the IA-2 antigen. METHODS: Autoantibodies against islet cell cytoplasm (ICA), insulin (IAA), GAD (GADA) and IA-2 (IA-2A) were measured at initial sampling in 1724 non-diabetic siblings (median age [range]:16 [0-39] years) of Type I diabetic patients with a median follow-up of 50 months. RESULTS: On initial sampling 11% of siblings were positive for one antibody type or more and 2.1% for three of more types. During follow-up, 27 antibody-positive siblings developed diabetes. Using survival analysis, the risk for clinical onset within 5 years was 34% in subjects positive for three or more types compared with 13% in those with one type or more. Progression to diabetes amounted to 12% within 5 years among siblings positive for IAA, 20% for ICA, 19% for GADA but 59% for IA-2A (p<0.001 vs absence of the respective antibody). IA-2A were detected in 1.7% of all siblings and in 56% of the prediabetic subjects on first sampling. Initial positivity for two or three antibody markers was associated with a higher progression rate in IA-2A positive as compared to IA-2A negative siblings (p=0.001). In absence of IA-2A initial positivity for another antibody (IAA, ICA or GADA) conferred a low (<10% within 5 years) risk of diabetes compared to subjects lacking this antibody. CONCLUSIONS/INTERPRETATION: In siblings of Type I diabetic patients, IA-2A positivity is a more direct predictor of impending clinical onset than multiple antibody positivity per se. Assessment of IA-2A status allows us to select subjects with homogeneously high risk of diabetes for participation in prevention trials.

Adolescent↗

An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major complications and 100-day transplant-related mortality after allogeneic bone marrow transplantation.

We monitored levels of C-reactive protein (CRP) in 96 consecutive adult allogeneic BMT patients (age 15-50 years) transplanted in our unit. Major transplant-related complications (MTC) occurred in 32% of cases and included: hepatic veno-occlusive disease, pneumonitis, severe endothelial leakage syndrome and >II acute GVHD. Transplant-related mortality (TRM) before day 100 post-BMT was 13.5%. Variables included in a stepwise logistic regression model were: gender, age, disease category, donor type, T cell depletion, TBI, use of growth factors, bacteremia, mean CRP-levels >50 mg/l between days 0 and 5 (CRP day 0-5) and >100 mg/l between days 6 and 10 (CRP day 6-10) post-BMT. Only high CRP-levels (for MTC and TRM) (P < 0.001) and donor-type (for TRM) (P= 0.02) were independent risk factors. The estimated probability for MTC was 73% (CRP day 6-10 >100 mg/l) vs 17% (CRP day 6-10 <100 mg/l). Using the same cut-off levels, the probabilities for TRM were 36.5% vs 1% in the identical sibling donor situation and 88% vs 12.5% in other donor-type transplants. We conclude that the degree of systemic inflammation, as reflected by CRP-levels, during the first 5-10 days after BMT identifies patients at risk of MTC and TRM. Our data may be useful in selecting patients for clinical trials involving pre-emptive anti-inflammatory treatment.

Adolescent↗

Efficacy of topical corticosteroids in nickel-induced contact allergy.

In this study we used the nickel contact allergy patch (CAP) test to investigate the effect of topical corticosteroids on allergic contact dermatitis (ACD). On day 1, three CAP tests were applied for 48 h on the forearms of 20 female volunteers with a known nickel ACD. CAP of the right forearm contained 5% nickel, and of the left forearm physiological saline. Clinical scoring, transepidermal water loss and skin hydration were measured on day 1 before CAP application, on day 4 (0, 2 and 6 h) after ACD and from days 5 to 8 (0 h). A topical corticosteroid and its vehicle were applied twice daily starting from day 4 on two ACD sites. Transepidermal water loss values were significantly decreased on the topical-corticosteroid-treated sites in the early phase of ACD (day 4, 6 h after the first application) while clinical efficacy showed significant improvement on days 7 and 8. The vehicle was found to improve skin hydration only on day 8. In conclusion the topical corticosteroid improved the skin barrier function in the early inflammatory phase of ACD (day 4, 6 h). The lack of improvement in transepidermal water loss in the later phase of ACD might be accounted for by the secondary effects of the corticosteroid on proliferation and differentiation of keratinocytes.

Administration, Cutaneous↗

A treatment scale for axillary management in breast cancer.

BACKGROUND: We have investigated a method, the Kaufman axillary treatment scale (KATS), to help assign patients with a clinically negative axilla to one of three current options of axillary management: standard axillary dissection, sentinel node sampling followed by axillary dissection if the sentinel node is positive, or no axillary surgery at all. The KATS score uses preoperative data to guide the choice of axillary treatment. METHODS: The KATS score is calculated by adding the preoperative values of tumor size, patient age, and pathologic grade. Values range from 1 to 4 for size (1 to 9 mm, 10 to 14 mm, 15 to 19 mm, and 20 to 30 mm), 1 to 3 for age (70 years and over, 50 to 69 years, less than 50 years), and 1 to 2 for grade (low or not low) to calculate the score. The KATS score ranges from 3 to 9. We have applied this score against the SEER (Surveillance, Epidemiology, and End Results) tumor registry of 529 patients with invasive breast cancer with known pathologic data. We then validated it by applying it to our own set of 190 patients using preoperative data. The chi-square test and logistic regression analysis were used for P values (all two sided), univariate and multivariate analysis, odds ratio and confidence intervals utilizing SPSS statistics software. RESULTS: In the SEER database using American Joint Committee on Cancer pathologic size alone, no sizable group was identified with a positive node rate neither below 8% (T1a) nor above 48% (T2). KATS scores of 3 and 4 (68 patients, group 1) identify patients with an average node positive rate of 4.4% (P <0.02, group 1 versus 2). Those patients with KATS scores of 5, 6, and 7 (341 patients, group 2) carry an average node positive rate of 22% (P <0.001, group 2 versus 3). KATS scores of 8 and 9 (120 patients, group 3) identify patients with an average node positive rate of 50% (P <0.001, group 3 versus 1). Similar results were found on our own group of 190 patients using preoperative available data. KATS scores of 3 or 4 (11 patients, group 1) had no positive nodes. Group 2 (100 patients, KATS score 5, 6, and 7) had an average 30% node positive rate. Group 3 (79 patients, KATS score 8 and 9) had 61% node positive rate. The KATS score allows the clinician to separate patients into three axillary management groups. Group 1 are those patients who may need no axillary surgery at all. Group 2 are patients who would benefit from sentinel node mapping. Group 3 has a node positive rate (61%) similar to that of clinically palpable nodes (since not all clinically palpable nodes are positive). Group 3 patients may be considered for standard axillary dissection, similar to the palpable node patient. If group 3 patients have sentinel node mapping, more than half of these patients require axillary dissection and the impact of false negative sentinel node procedures may become clinically significant. CONCLUSIONS: An axillary treatment score has been developed to aid in the triage of patients toward reasonable axillary treatment choices for the benefit of the patient. The KATS score is a guideline and not a mandate. The KATS score attempts to use breakpoints that are both clinically practical and validated by scientific data. Like many other attempts to categorize patients, there is a continuum of data points along any variable. The treating physician utilizing the full array of available data on each patient makes the final clinical decision of axillary management.

Age Factors↗

Effect of interferon alpha-2b on endometrioma cells in vitro.

OBJECTIVE: To examine the effect of interferon alpha-2b on the growth of endometrioma cells and its effect on the DNA synthesis. METHODS: Cells from four separate endometrioma cell lines were seeded into six-well plates in M199 medium containing increasing levels of interferon alpha-2b: 0 (control), 50, 100, 500, 1000, and 2000 U/mL. All cells were counted on days 0, 3, 6, and 9 in quadruplicate, and the counts were averaged for each condition. A second experiment was run to demonstrate the effect of short-term exposure of interferon alpha-2b on the growth of endometrioma cells in culture. In a separate experiment, cells from two endometriomas were plated in quadruplicate to evaluate the DNA synthesis. On day 3, 1000 and 4000 U/mL of interferon alpha-2b were added and run simultaneously with control (0 U/mL) wells. 3H-thymidine was added to each condition for 24 and 48 hours' incubation. Cells were then harvested and counted in a scintillation counter to study the 3H-thymidine uptake. RESULTS: Interferon alpha-2b suppressed endometrioma cell growth in vitro. This effect increased with increasing concentrations of interferon alpha-2b (50-2000 U/mL) compared with the control (0 U/mL). The suppression of cell growth was statistically significant, but when interferon alpha-2b was removed from the culture cell growth increased. 3H-thymidine uptake by endometrioma cells decreased compared with the control after 24 and 48 hours for interferon alpha-2b concentrations of 1000 and 4000 U/mL, respectively. CONCLUSION: Interferon alpha-2b inhibits the growth and DNA synthesis of endometrioma cells in culture. This finding may have prospects for the treatment of endometriosis.

Antineoplastic Agents↗

Comparison of immunohistochemical and biochemical measurement of steroid receptors in breast cancer: are both still necessary?

In our institute, the oestrogen and progesterone receptors of breast cancer samples are analyzed by biochemistry and immunohistochemistry. The purpose of this study is to evaluate and compare both techniques and establish whether one of them should be used in preference to the other. The probability of getting a positive or negative result with each technique was the same regardless of the method used as reference. The biochemical method uses a larger volume of tissue to determine the receptor status than immunohistochemistry. In some cases, this means a loss of valuable information. If we only use one technique, there is the potential to misclassify +/- 11% of patients. According to these results and in the knowledge that the major interest of steroid receptors' status remains in the domain of therapeutic decisions, we advise using immunohistochemistry first and biochemistry if there is a negative result. This would spare tumour tissue for new research studies.

Journal Article↗

PH monitoring in the distal and proximal esophagus in symptomatic infants.

BACKGROUND: Standard distal esophageal pH monitoring data are sometimes within normal ranges in children with clinically suspected gastroesophageal reflux disease. Therefore, the authors hypothesized that the amount of acid reflux reaching the proximal esophagus may be greater in some subgroups of patients than in healthy controls or in other subgroups of patients. METHODS: The parameters of 24-hour pH monitoring in the proximal part of the esophagus were analyzed in 120 symptomatic infants in who the reflux parameters in the lower esophagus were clearly within normal ranges (reflux index < 5.0%). The infants were classified into four patient groups: excessive regurgitation (n = 41): inconsolable crying (n = 31), apparent life-threatening event (ALTE) (n = 18), and chronic respiratory disorders (n = 30). The control group consisted also of 120 infants. The following parameters were calculated: reflux index, the number of reflux episodes, the number of reflux episodes lasting longer than 5 minutes, the duration of the longest reflux episode, and the acid clearance time (ACT, duration of reflux episodes divided by number of reflux episodes). RESULTS: The patients with chronic respiratory disorders were significantly older than the patients in the other groups and the controls. In the distal esophagus, there was no statistically significant difference between the reflux parameters. As could be expected, every parameter was statistically (paired t test, Wilcoxon signed-rank test) significantly smaller in the proximal than in the distal esophagus, except for the ACT in infants who presented with inconsolable crying. In the proximal esophagus, there was no statistically significant difference between the different patient subgroups or controls, except for the number of reflux episodes in the group with chronic respiratory disorders and the group with inconsolable crying, applying one-way analysis of variance. As determined by applying the Mann-Whitney test, the number of reflux episodes in the upper esophagus was significantly higher in the group with chronic respiratory disorders than in the other patient groups and controls. Therefore, the authors' data do not support the hypothesis that reflux reaching the proximal esophagus is a frequent cause of ALTE. However, the data may suggest that the number of reflux episodes reaching the proximal esophagus in children with chronic respiratory disorders and with distal pH monitoring data within normal ranges may be increased. Whether this finding reflects reality or a statistical coincidence, or is influenced by the older age of this patient group, needs further evaluation. CONCLUSIONS: In theory, dual simultaneous esophageal pH monitoring in the distal and proximal esophagus may increase the diagnostic accuracy of pH monitoring in infants. Our results do not support a substantial advantage of a systematic application of this new technique, especially not in infants presenting with ALTE, excessive regurgitation, or inconsolable crying. In the subgroup of patients with chronic respiratory disorders, more data are needed before conclusions can be determined and recommendations can be made.

Cohort Studies↗

Combination therapy improves the recovery of the skin barrier function: an experimental model using a contact allergy patch test combined with TEWL measurements.

BACKGROUND: Nickel (Ni) allergic contact dermatitis (ACD) alters the skin barrier. OBJECTIVE: Our aim was to compare the efficacy of combination therapies on ACD, using a topical corticosteroid and a corneotherapy agent (barrier cream), with that of a single therapy with corticosteroids. METHODS: On day 1, 3 Ni test patches were applied on each forearm of 14 Ni-patch-test-positive females. Four contained 5% Ni and 2 physiological saline. Either topical corticosteroid or barrier cream were matched with the combination of both products on 3 of the 4 Ni ACD. The fourth was not treated. Clinical scoring, transepidermal water loss (TEWL) and stratum corneum (SC) capacitance were measured before (day 1) and after (days 4-8) ACD. RESULTS: The combination therapy showed a significant decrease in TEWL values and an increase in SC capacitance. CONCLUSION: Combining a topical corticosteroid with corneotherapy agents prevents the delay in the healing process of skin barrier disruption due to ACD.

Administration, Cutaneous↗

Attitudes and knowledge about cancer pain in Flanders. The educational effect of workshops regarding pain and symptom control.

Despite international agreements and recommendations regarding cancer pain therapy, the effectiveness of pain treatment is still a major problem even in Western countries. Part of the problem is that physicians and nurses often lack knowledge of methods for the assessment and treatment of cancer pain and may have many rigid beliefs and attitudes. This study investigated the misconceptions of physicians and nurses that play a role in the undertreatment of pain in Flanders (Belgium). We approached 197 health care workers who participated in the pain and symptom control education sessions organized by the Federation Palliative Care Flanders, and asked them to complete a questionnaire both before and after the sessions. The impact of the education sessions on their knowledge and beliefs regarding the management of cancer pain was substantial. Methods of reaching the target groups that do not feel the need for further education are discussed.

Analgesics, Opioid↗

Ghost imaging in MRI.

Needle biopsies and other interventions done under MR Fluoroscopy sometimes do not show the target well, either because the rapid sequence does not have adequate contrast or because a contrast agent may have washed out of the target. In these cases, an image that shows the target can be saved and scaled to match the spatial parameters of the fluoroscopic sequence, and used as a virtual or ghost field upon which the fluoroscopic images are superimposed, thus providing a view of the target, useful for needle pre-localization and for monitoring its progress as it is inserted.

Biopsy, Needle↗