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Biomedical subjects

S Stern

Publications and source records attributed to S Stern.

At least 19 recordsLinked to original sources
PubMed2002

Approaches to interval mapping of QTL in a multigeneration pedigree: the example of porcine chromosome 4.

Quantitative trait loci (QTLs) have been mapped in many studies of F2 populations derived from crosses between diverse lines. One approach to confirming these effects and improving the mapping resolution is genetic chromosome dissection through a backcrossing programme. Analysis by interval mapping of the data generated is likely to provide additional power and resolution compared with treating data marker by marker. However, interval mapping approaches for such a programme are not well developed, especially where the founder lines were outbred. We explore alternative approaches to analysis using, as an example, data from chromosome 4 in an intercross between wild boar and Large White pigs where QTLs have been previously identified. A least squares interval mapping procedure was used to study growth rate and carcass traits in a subsequent second backcross generation (BC2). This procedure requires the probability of inheriting a wild boar allele for each BC2 animal for locations throughout the chromosome. Two methods for obtaining these probabilities were compared: stochastic or deterministic. The two methods gave similar probabilities for inheriting wild boar alleles and, hence, gave very similar results from the QTL analysis. The deterministic approach has the advantage of being much faster to run but requires specialized software. A QTL for fatness and for growth were confirmed and, in addition, a QTL for piglet growth from weaning at 5 weeks up to 7 weeks of age and another for carcass length were detected.

Alleles↗
PubMed2002

Biochemical intestinal parameters in pigs reared outdoors and indoors, and in germ-free pigs.

Intestinal microbial functions reflect cross-talk between a host and its flora, and external factors may influence these functions. The aim of this investigation was to follow the development of six biochemical microbial-related functions of piglets, raised outdoors (OPs) or indoors (IPs), from birth to slaughter age. The following parameters (microflora-associated characteristic; MAC) were consecutively measured at five different ages: production of short-chain fatty acids (SCFA), conversion of cholesterol to coprostanol and of bilirubin to urobilinogens, inactivation of trypsin, degradation of beta-aspartylglycine and of mucin. Additionally, four parameters (production of SCFA. conversion of cholesterol to coprostanol, inactivation of trypsin, degradation of beta-aspartylglycine) were investigated in faecal samples from germ-free minipigs. The differences in MAC patterns between OPs and IPs were most pronounced at 20 days of age. Differences were found in the total amount of SCFAs, proportions of the acetic, propionic and butyric acids, conversion of bilirubin to urobilinogens, degradation of faecal tryptic activity and degradation of mucin. The values found in the minipigs were within the range of a germ-free animal characteristic (GAC) pattern. Our results show that environmental factors influence the development of some intestinal microbial functions in pigs.

Animal Husbandry↗
PubMed2001

Tumor-associated antigen TA90 immune complex assay predicts recurrence and survival after surgical treatment of stage I-III melanoma.

PURPOSE: Immune complexes (IC) containing the tumor-associated antigen TA90 can be identified in the sera of melanoma patients. We have shown that an enzyme-linked immunosorbent assay for TA90-IC can detect subclinical metastasis before surgical treatment of early-stage melanoma. We assayed the TA90-IC levels of postoperative sera from patients with melanoma and evaluated their relationship to recurrence and survival. PATIENTS AND METHODS: Multiple archival serum samples prospectively collected during postoperative surveillance of 166 patients with American Joint Committee on Cancer stage I, II, or III melanoma were analyzed for TA90-IC in a blinded fashion. Results were correlated with disease recurrence and survival determined by database and chart review. RESULTS: TA90-IC status in the early postoperative period was strongly correlated with survival. Five-year overall survival rates were 84% for TA90-IC-negative patients and 36% for TA90-IC-positive patients (P =.0001). Respective 5-year disease-free survival rates were 74% and 24% (P =.0001). The TA90-IC assay was a significant predictor of survival for both stage II and III patients. Multivariate analysis identified TA90-IC status as the strongest independent prognostic factor for both overall and disease-free survival. The TA90-IC assay was elevated in 54 (77%) of 78 patients who developed recurrent disease, becoming positive 19 +/- 7 months before clinical evidence of recurrence. Overall, the assay detected recurrence with a sensitivity of 78% and specificity of 77%. Exclusion of patients receiving postoperative immunotherapy with a polyvalent melanoma cell vaccine increased sensitivity and specificity to 92% and 86%, respectively. CONCLUSION: The TA90-IC assay can accurately predict survival and detect the presence of subclinical disease after surgery for melanoma, which should be useful in selecting patients for adjuvant therapy. Because the TA90-IC assay detected recurrence on an average of 19 months sooner than did routine clinical and radiographic evaluation, it may allow more timely therapeutic interventions.

Antigens, Neoplasm↗
PubMed2001

Perinatal and lifetime exposure to methylmercury in the mouse: blood and brain concentrations of mercury to 26 months of age.

Chronic, low-level exposures to environmental toxicants, because they often begin prenatally and then persist throughout the individual's lifetime, pose challenging issues to risk assessment. Exposure to low levels of methylmercury through the diet, based largely on consumption of fish and sea mammals, follows this pattern. Early development is considered to be a period of heightened vulnerability during which even low-level exposures may produce undetected, "silent", damage that is revealed only under conditions that challenge the functional capacities of the individual. Aging, with its diminished functional capacities and compensatory reserves provides such a challenge, but, to explore this possibility, requires basic information about blood and brain levels under conditions of chronic lifetime exposure. The current research was undertaken to provide such information. One hundred female B6C3F1/HSD mice were assigned to one of three dose groups, 0, 1, or 3 ppm methylmercury chloride administered in a 5 nM sodium carbonate drinking solution. They were bred with male CBA/J HSD mice to produce the trihybrid offspring B6C3F1/ HSD x CBA/J HSD. Dosing of the females began 4 weeks prior to breeding and continued for the two methylmercury-exposed groups throughout breeding and gestation. The methylmercury-treated litters were split into two subgroups, one exposed throughout its lifetime (set at 26 months) to the original dose, the other exposed through postnatal day 13 (PND 13). Brain and blood concentrations were assayed by cold-vapor atomic absorption. Samples were obtained on PND 4 and 21, and then at the end of months 14 and 26. On PND 4, brain and blood levels closely reflected maternal dosing. In all groups, concentrations fell sharply from PND 4 to 21, but to a greater extent in the perinatal groups. Blood levels in the 1 ppm lifetime group remained unchanged between months 14 and 26, but brain levels rose modestly. In the 3 ppm lifetime group, both brain and blood levels rose significantly between months 14 and 26, suggesting an interaction between dose and age.

Age Factors↗
PubMed2001

Sentinel lymph nodes show profound downregulation of antigen-presenting cells of the paracortex: implications for tumor biology and treatment.

The sentinel lymph node (SN) is the first node on the direct lymphatic drainage pathway from a tumor. Melanoma-associated SNs are the most likely site of early metastases and their immune functions are strikingly down-modulated. We evaluated histologic and cytologic characteristics of 21 SNs and 21 nonsentinel nodes (NSNs) from melanoma patients who had clinically localized (AJCC Stage I--II) primary cutaneous melanoma. SNs showed highly significant reductions in total paracortical area and in the area of the paracortical subsector occupied by dendritic cells. The frequency of paracortical interdigitating dendritic cells (IDCs) was dramatically reduced in SNs, and most IDCs (approximately 99%) lacked the complex dendrites associated with active antigen presentation. The release of immunosuppressive factors from the primary melanoma may induce a localized and specific paralysis in the SN, which prevents the recognition of otherwise immunogenic melanoma antigens by IDCs. This immune paralysis may facilitate the implantation and growth of melanoma cells in the SN. Cytokine therapy may be able to reverse this immune paralysis. These findings have an important practical application in the histopathologic confirmation that a node is truly sentinel. They also offer an hypothesis to explain the failure of the immune surveillance mechanisms to identify and respond to a small primary melanoma that expresses immunogenic tumor antigens.

Antigen-Presenting Cells↗
PubMed2001

The peripheral vascular response to exercise is impaired in patients with risk factors for coronary artery disease.

BACKGROUND: Abnormal coronary and brachial artery responses have been described in individuals with risk factors for coronary artery disease (CAD). Peripheral arterial tonometry (PAT), a newly developed digital plethysmographic technique was used to assess peripheral vascular response to exercise in healthy controls and individuals with risk factors. METHODS AND RESULTS: Continuous finger PAT during Bruce protocol exercise test was performed in 30 subjects with risk factors for CAD and 30 healthy individuals. Compared with baseline, the PAT wave amplitude at peak exercise decreased in the subjects but increased in the controls: 83 +/- 28% vs. 114 +/- 40% respectively, p < 0.01. CONCLUSIONS: A different pattern of systemic vascular response to exercise was found in individuals with risk factors for atherosclerosis. Since the vascular behavior in these patients is probably related to endothelial dysfunction, it may be that peripheral arterial tonometry can be used as a simple, readily available technique to assess endothelial function.

Adult↗
PubMed2001

Altered operant responding for motor reinforcement and the determination of benchmark doses following perinatal exposure to low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Pregnant Holtzman rats were exposed to a single oral dose of 0, 20, 60, or 180 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the 18th day of gestation. Their adult female offspring were trained to respond on a lever for brief opportunities to run in specially designed running wheels. Once they had begun responding on a fixed-ratio 1 (FR1) schedule of reinforcement, the fixed-ratio requirement for lever pressing was increased at five-session intervals to values of FR2, FR5, FR10, FR20, and FR30. We examined vaginal cytology after each behavior session to track estrous cyclicity. Under each of the FR values, perinatal TCDD exposure produced a significant dose-related reduction in the number of earned opportunities to run, the lever response rate, and the total number of revolutions in the wheel. Estrous cyclicity was not affected. Because of the consistent dose-response relationship at all FR values, we used the behavioral data to calculate benchmark doses based on displacements from modeled zero-dose performance of 1% (ED(01)) and 10% (ED(10)), as determined by a quadratic fit to the dose-response function. The mean ED(10) benchmark dose for earned run opportunities was 10.13 ng/kg with a 95% lower bound of 5.77 ng/kg. The corresponding ED(01) was 0.98 ng/kg with a 95% lower bound of 0.83 ng/kg. The mean ED(10) for total wheel revolutions was calculated as 7.32 ng/kg with a 95% lower bound of 5.41 ng/kg. The corresponding ED(01) was 0.71 ng/kg with a 95% lower bound of 0.60. These values should be viewed from the perspective of current human body burdens, whose average value, based on TCDD toxic equivalents, has been calculated as 13 ng/kg.

Administration, Oral↗
PubMed2000

Sex differences in management and outcome after acute myocardial infarction in the 1990s: A prospective observational community-based study. Israeli Thrombolytic Survey Group.

BACKGROUND: Previous studies have suggested that women with acute myocardial infarction (AMI) are less aggressively managed than are men. The aim of this study was to assess sex differences in medical and invasive coronary procedures (angiography, PTCA, and CABG) in AMI patients admitted to cardiac care units (CCUs) in Israel in the mid 1990s and their association with early and 1-year prognosis. METHODS AND RESULTS: We studied 2867 consecutive AMI patients (2125 men, 74%) hospitalized in all 25 CCUs in Israel from 3 prospective nationwide surveys conducted in 1992, 1994, and 1996. Women were, on average, older than men (69 versus 61 years, P:<0.0001) and had a higher prevalence of hypertension, diabetes, Killip class >/=II on admission, and in-hospital complications. Women received aspirin and beta-blockers less often than did men, but these differences were not significant after age adjustment. The unadjusted rates of thrombolysis, angiography, and PTCA/CABG use were lower in women than in men but not after covariate adjustment: 42% versus 48% (adjusted odds ratio [OR] 0.92, 95% CI 0.77 to 1.11), 23% versus 31% (OR 0.88, 95% CI 0.70 to 1.09), and 15% versus 19% (OR 0.93, 95% CI 0.72 to 1.19), respectively. The 30-day mortality was higher in women than in men (17.6% versus 9.6%, respectively; OR 1.39, 95% CI 1.06 to 1.82), but the 30-day to 1-year mortality rate was not (9.1% versus 5.6%, respectively; hazard ratio 1.18, 95% CI 0.84 to 1.66). CONCLUSIONS: This prospective nationwide observational community-based study of consecutive AMI patients hospitalized in the CCUs in the mid 1990s indicates that women fare significantly worse than do men at 30 days but not thereafter at 1-year. The difference in 30-day outcome was not influenced by the use of different therapeutic modalities, including thrombolysis and invasive coronary procedures, but was rather due to the older age and greater comorbidity of women; these findings seem also to explain the less frequent use of invasive procedures in women.

Age Distribution↗
PubMed2000

Serotonergic antidepressants and urinary incontinence.

Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.

Adult↗
PubMed2000

Solid facial edema preceding a diagnosis of retro-orbital B-cell lymphoma.

Persistent solid facial edema is a rare condition of unknown cause. Although acute facial edema has been associated with numerous disease processes such as infections, neoplasms, immune disorders, inflammation, neuropathic processes, drugs, mechanical obstructions, and trauma, solid facial edema has most often been associated with acne vulgaris. We report the first case, to our knowledge, of solid facial edema preceding a diagnosis of a subcutaneous scalp and orbital/periorbital B-cell lymphoma.

Aged↗
PubMed2000

Weekly alternating combination chemotherapy for good prognosis AIDS-related lymphoma.

Early studies reported that the major adverse prognostic factors in AIDS-related non-Hodgkin's lymphoma (ARL) are low CD4 cell count, prior AIDS defining diagnosis and poor performance status. Since 1989 we have adopted a prognosis-stratified approach for ARL. In this study, we identified a group of good prognosis patients. These patients with one or no adverse prognostic factors were treated with alternating weekly chemotherapy using the bleomycin, etoposide, vincristine, methotrexate, prednisolone/cyclophosphamide, doxorubicin (BEMOP/CA) schedule (Bower M, Block C, Gulliford T, et al. Cancer Chemother Pharmacol 1995, 38, 106-109). Modifications to the regimen with the aim of reducing toxicity were a briefer duration (12 weeks) and the addition of prophylaxis against pneumocystis and mycobacteria. Intrathecal methotrexate was administrated fortnightly to patients with Burkitt's histology, meningeal involvement or base of skull disease. 30 patients were treated, including 5 with prior AIDS, 3 with ECOG status 3 and 1 with CD4 <100/microl. The mean age was 40 (range 22-60 years), the median CD4 cell count at ARL diagnosis was 262/microl (range 44-588/microl). The International non-Hodgkin's lymphoma (NHL) prognostic factors project classifications were low risk 8 (maximum 5.4 years) (27%), low-intermediate risk 6 (20%), high-intermediate risk 11 (37%) and high risk 5 (17%). The median follow-up was 2.1 years. 3 patients withdrew from treatment within 2 weeks due to toxicity, 2 patients died within 2 weeks of starting chemotherapy. The major toxicity was myelosuppression with 14 patients developing grade 4 neutropenia. The 2-year overall survival rate is 46% (95% confidence interval (CI)=27-65%), and lymphoma-specific survival at 2 years is 59% (95% CI: 40-78%). For selected patients with good prognosis ARL 12 weeks BEMOP/CA therapy produces good overall survival at 2 years.

Adult↗
PubMed2000

Mortality trends in men and women with acute myocardial infarction in coronary care units in Israel. A comparison between 1981-1983 and 1992-1994. For the SPRINT and the Israeli Thrombolytic Survey Groups.

AIMS: To assess trends in the management and subsequent outcome in men and women in two cohorts of consecutive patients with acute myocardial infarction hospitalized in coronary care units in Israel, in the pre-reperfusion and the reperfusion eras. METHODS AND RESULTS: We compared trends in the in-hospital management, and 30-day and 1-year mortality in men and women in two cohorts of patients hospitalized with acute myocardial infarction in coronary care units in Israel, in the pre-reperfusion and the reperfusion eras. The first cohort of 5839 consecutive patients (4315 men, 74%) was from the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) registry of 1981-1983; the second cohort of 1940 patients (1429 males, 74%) derived from two prospective nationwide surveys conducted in all coronary care units in Israel in January/February 1992 and 1994. The demographic and clinical characteristics of patients with acute myocardial infarction in both periods were comparable. Patients in 1992-94 received aspirin, angiotensin-converting enzyme inhibitors, beta-blockers and nitrates more frequently than in 1981-83. Thrombolysis, coronary angiography, angioplasty and bypass grafting were not used in 1981-83, whereas in 1992-94 these procedures were used in 45%, 28%, 11% and 4% of men, respectively, and in 39%, 20%, 9% and 3% of women, respectively. The 30-day age-adjusted mortality declined, in men, from 17.0% in 1981-83 to 10.8% in 1992-94 (multivariate-adjusted odds ratio [OR]=0. 69; 95% confidence interval [CI] 0.55 to 0.87), and the cumulative 1-year age-adjusted mortality declined from 24.6% to 16.9% (adjusted hazard ratio [HR]=0.70%; 95% CI 0.60 to 0.81). In women, the decline in mortality rates were of similar magnitude, from 24.0% to 15.1% (OR=0.70; 95% CI 0.52 to 0.94), and from 33.6% to 21.0% (HR=0.67; 95% CI 0.55 to 0.81), respectively. In both sexes, the decline in mortality was more marked in patients reperfused by thrombolysis and/or mechanical revascularization, but was also evident in non-reperfused patients. CONCLUSIONS: Despite higher mortality in both periods in women compared to men, the prognosis of men and women with acute myocardial infarction improved considerably during the last decade, with a similar decline in 1-year mortality of approximately 30%. The implementation in daily practice of new therapeutic modalities proven to be effective in clinical trials after acute myocardial infarction, probably played a major role in this favourable outcome in both sexes.

Aged↗
PubMed2000

Cultivation of porcine cells from the nucleus pulposus in a fibrin/hyaluronic acid matrix.

Use of multiplied viable cells from the nucleus pulposus in altered discs, following in vitro cultivation, may be a promising therapy for degenerative disc disease. Up till now, alginate has been used as a three-dimensional cell carrier to cultivate nucleus pulposus cells. However, the biocompatibility of the alginate, which depends on the composition and purity of alginate materials used, has not been considered for in vivo application so far. In this study, we cultured porcine cells from the nucleus pulposus in a mixture of fibrin and hyaluronic acid (HA). The DNA content and proteoglycan synthesis were compared to those measured in an alginate matrix. Although the increase in DNA content was 2.5-fold higher in the alginate culture after 3 weeks, the proteoglycan synthesis in relation to the DNA content was significantly higher in the fibrin/HA matrix. We found that the fibrin/hyaluronic acid matrix can be used as a substrate for in vitro cultivation.

Animals↗
PubMed2000

Mechanical properties of small fragment screws.

For many years, stainless steel small fragment screws have been produced by one manufacturer. Recently, other implant makers have begun offering similar stainless steel screws. In addition, screw geometry and material composition have been modified in an attempt to produce screws for a wide range of clinical situations. This study compared the mechanical properties of several commonly used small fragment screws. Seven sets of screws were tested mechanically, including three brands of geometrically identical standard stainless steel cortical screws and one brand each of cannulated stainless steel cortical screws, titanium cortical screws, stainless steel cancellous screws, and bioabsorbable polylactic acid screws. Screws from each group were tested for pullout strength, torque to failure, and three-point bending to failure. There were no differences in the mechanical properties of the identical 3.5-mm standard stainless steel cortical screws. No difference in pullout strength was found between the five sets of cortical screws. However, the cancellous screws had 4% to 24% less pullout strength. Torsion tests showed that cannulated stainless steel cortical, titanium cortical screws, stainless steel cancellous screws, and polylactic acid screws failed at significantly less torque than did standard stainless steel cortical screws. Standard stainless steel cortical screws had the highest mean yield point and maximal load at failure of all screws in three-point bending. Other metal screws had lower yield strength and maximal load at failure than did the standard stainless steel cortical screws, and polylactic acid screws had the least bending strength.

Biomechanical Phenomena↗
PubMed2000

HLA-DR and beta 2 microglobulin expression in medullary and atypical medullary carcinoma of the breast: histopathologically similar but biologically distinct entities.

AIMS: To examine the expression of HLA-DR and beta 2 microglobulin in medullary carcinoma and atypical medullary carcinoma of the breast to determine if the effective presentation of tumour antigens to the immune system can differentiate between these two histopathologically similar entities. METHODS: Expression of HLA-DR and beta 2 microglobulin was examined by immunohistochemical methods in five samples of medullary carcinoma of the breast, which has a relatively favourable prognosis, six samples of atypical medullary carcinoma of the breast, which has a prognosis closer to that of regular invasive duct carcinoma, and 20 samples of invasive duct carcinomas, 10 with an accompanying lymphocytic infiltrate. RESULTS: A positive and significant correlation was found between tumour type and both HLA-DR and beta 2 microglobulin expression. Expression was most prominent in medullary carcinoma, followed by atypical medullary carcinoma and invasive duct carcinoma with and without lymphocytic infiltrates. The mean intensity and percentage of HLA-DR tumour immunostaining were significantly higher in medullary carcinoma than in the other three tumour groups, as was the mean intensity of beta 2 microglobulin immunostaining. Mean percentage of beta 2 microglobulin immunostaining was significantly higher in medullary carcinoma than in invasive duct carcinoma without lymphocytic infiltrates, and showed a trend to increase from invasive duct carcinoma with lymphocytic infiltrates to atypical medullary carcinoma and medullary carcinoma. CONCLUSIONS: Medullary carcinoma and atypical medullary carcinoma of the breast differ in their expression of HLA-DR and beta 2 microglobulin. The relatively favourable prognosis of medullary carcinoma of the breast may be related to effective tumour antigen presentation to the immune system through MHC-I and MHC-II expression. Immunotherapy aimed at MHC-I and MHC-II induction might have a beneficial effect in breast cancer.

Adult↗