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Biomedical subjects

J Epstein

Publications and source records attributed to J Epstein.

At least 19 recordsLinked to original sources
PubMed2006

A multistate cluster of red blood cell transfusion reactions associated with use of a leucocyte reduction filter.

In 2000, the American Red Cross (ARC) received reports of unusual transfusion reactions of unknown aetiology among patients receiving leucocyte-reduced (LR) red blood cell (RBC) units in multiple distribution regions. We evaluated potential risk factors of reactions among patients who received LR-RBC transfusions. A case-patient was defined as any patient with onset of back pain while receiving an LR-RBC transfusion from 1 January to 25 May 2000. Controls were chosen randomly and selected in a 1:3 case : control ratio from healthcare facilities in which case-patients were transfused. Product-specific risk factors of reactions were further determined through nested case-control study, procedural review of blood collection facility and quality-control-testing record review of product processing. Reaction incidence rates were determined through ARC blood product distribution data by region of blood collection and processing. There were 29 reactions detected in patients who received transfusions in 13 healthcare facilities in five states. Eighteen case-patients and 78 controls were included in the case-control study. In univariate analysis, case-patients were more likely than controls to have a haematologic malignancy, to have received the transfusion as an outpatient, to have received an RBC transfusion within the previous 3 months, to have received medication used to prevent reactions or to diminish their intensity upon transfusion (i.e. premedication) or to have received LR-RBC units prepared with the HemaSure r\LS System(HS) rather than two other filters used. In multivariate analysis limited to recipients of HS-filtered RBC units, transfusion premedication [adjusted odds ratio (AOR) = 7; 95% confidence interval (CI) 1.4-37; P = 0.02] and transfusion as an outpatient (AOR = 5; 95% CI 1.1-20; P = 0.03) were independently associated with reactions. The rate of reported transfusion reactions was 2.0 reactions per 10 000 RBC units distributed. A multistate cluster of transfusion reactions was significantly associated with leucocyte filtration of RBC units prepared with a specific product, the HS filter. The reactions also were independently associated with premedication and transfusion as an outpatient; these may be surrogates for an increased risk of reaction or for greater likelihood of detection. The mechanism for these reactions has not been elucidated. This cluster of reactions underscores the importance of surveillance efforts to detect adverse events after transfusion, particularly when new methods to modify blood products are introduced.

Adolescent↗
PubMed2005

Rectal intussusception in symptomatic patients is different from that in asymptomatic volunteers.

BACKGROUND: Rectal intussusception is a common finding at evacuation proctography in both symptomatic and asymptomatic individuals. Little information exists, however, as to whether intussusception morphology differs between patients with evacuatory dysfunction and healthy volunteers. METHODS: Thirty patients (19 women; median age 44 (range 21-76) years) with disordered rectal evacuation, in whom an isolated intussusception was seen on proctography, were studied. Various morphological parameters were measured, and compared with those from 11 asymptomatic controls (six women; median age 30 (range 24-38) years) found, from 31 volunteers, to have rectal intussusception. Intussusceptum thickness greater than 3 mm was designated as full thickness. Intussuscepta impeding evacuation were deemed to be occluding. RESULTS: Twenty-two patients had full-thickness intussusception, compared with two controls (P = 0.003). Intussusceptum thickness was significantly greater in the symptomatic group (anterior component: P = 0.004; posterior: P = 0.011). Twenty patients in the symptomatic group, but only three subjects in the control group, had a mechanically occluding intussusception (P = 0.043), although only three patients demonstrated evacuatory dynamics outside the normal range. CONCLUSION: Rectal intussusception in patients with evacuatory dysfunction is more advanced morphologically than that seen in asymptomatic controls; it is predominantly full thickness in patients and mucosal in controls. However, caution is required when selecting patients for intervention based solely on radiological findings.

Adult↗
PubMed2005

Endoanal ultrasound-guided needle drainage of intersphincteric abscess.

Traditional management of intersphincteric abscess is by incision and drainage involving division of fibres of the internal sphincter. Here, a less invasive method is described. Three patients with intersphincteric abscess identified by endoanal sonography were treated by ultrasound-guided needle aspiration under anaesthesia. None of the patients had complications or required postoperative wound care. All patients remained asymptomatic at a mean follow-up of 15.7 months (range, 12-18 months). Endoanal ultrasound-guided aspiration is a simple and safe method for the treatment of intersphincteric abscess.

Abscess↗
PubMed2005

Selecting the future doctors: the role of graduate medical programmes.

Graduate-entry medical programmes have been introduced in many Australian states. This has coincided with the introduction of learner-centred, problem-orientated medical courses and has resulted in a need to develop new selection pathways. Medical schools have complemented their primary selection tool of academic performance with tests of personal attributes considered important in future doctors. Schools with graduate-entry programmes now employ a combination of the results of the applicant's undergraduate degree, a semistructured interview and a psychometric test (the Graduate Australian Medical School Admissions Test) to select students. Rationale for the change to graduate entry and the outcomes of this change will be discussed.

Australia↗
PubMed2004

Surface anatomy of the inferior epigastric artery in relation to laparoscopic injury.

The inferior epigastric artery (IEA) is at risk of injury in laparoscopic surgery. Current descriptions of the course of the IEA do not provide surface landmarks useful to the surgeon. This study aimed to define surface relations and propose guidelines for safer trocar placement. The posterior surfaces of the anterior abdominal walls of 30 preserved cadavers were dissected. The surface anatomy of 60 IEAs and their branches were defined. At the level of the anterior superior iliac spine (ASIS), the IEA is 38% +/- 18% (95% confidence interval [CI]) from the midline to the ASIS. At the mid-inguinal point the relation is 40% +/- 17% and at the umbilicus 40% +/- 22%. The pattern of branches is highly variable. Although giving guidelines for trocar insertion can be treacherous, we found the following to be of value: 1) the midline is avascular; 2) the main stem of the IEA will be avoided if trocars are inserted more than two-thirds of the distance along a horizontal line between the midline and the ASIS; and 3) IEA branches are least frequently found in the lowest part of the abdomen lateral to the artery.

Aged↗
PubMed2003

Effect of fragile X status categories and FMRP deficits on cognitive profiles estimated by robust pedigree analysis.

The effect of the fragile X pre-mutation and full mutation categories, and FMRP deficits in these categories, on neurocognitive status, have been assessed in fragile X individuals from 144 extended families, which included fragile X individuals, as well as their non-fragile X relatives. Neuropsychological status was assessed by the Wechsler summary and subtest test scores. A modification of the maximum likelihood estimators for pedigree data that is resistant to outliers was used to analyze the data. The results have demonstrated the effect of large expansions of CGG repeat in the FMR1 (fragile X mental retardation 1) gene (full mutation) in decreasing full scale IQ (FSIQ), as well as several FSIQ-adjusted subtest scores in the performance domain. Moreover, the results have demonstrated significant cognitive deficits in male individuals with pre-mutation. FMRP depletion correlates strongly with neurocognitive status in the full mutation subjects. Evidence for the effect of FMRP in smaller expansions (pre-mutation) in reducing FSIQ, Performance and Verbal scores, as well as subtest scores in males, has also been obtained. The results are also suggestive of factors other than FMRP deficit which may determine some specific cognitive deficits in fragile X pre-mutation carriers. Genetic variance estimated from the models accounts for less than half of the total variance in FSIQ, and it varies widely between individual Wechsler subtests.

Female↗
PubMed2002

Prophylaxis of radiation-associated mucositis in conventionally treated patients with head and neck cancer: a double-blind, phase III, randomized, controlled trial evaluating the clinical efficacy of an antimicrobial lozenge using a validated mucositis scoring system.

PURPOSE: Mucositis occurs in almost all patients treated with radiotherapy for head and neck cancer. The aim of this multicenter, double-blind, prospective, randomized trial was to evaluate the clinical efficacy of an economically viable antimicrobial lozenge (bacitracin, clotrimazole, and gentamicin [BcoG]) in the alleviation of radiation-induced mucositis in patients with head and neck cancer. PATIENTS AND METHODS: One hundred thirty-seven eligible patients were randomized to treatment with either antimicrobial lozenge (69 patients) or placebo lozenge (68 patients). The primary end point of the study was the time to development of severe mucositis from the start of radiotherapy. Secondary end points included severity and duration of mucositis, pain measurement, radiation therapy interruption, and quality of life. Mucositis was scored using a validated mucositis scoring system. RESULTS: Toxicity profiles were similar between the two arms of the study. The median time to development of severe mucositis from the start of radiotherapy was 3.61 weeks on BCoG and 3.96 weeks on placebo (P =.61). There were no statistically significant differences between the arms in the extent of severe mucositis as measured by physician, in oral toxicities as recorded by patients, or in radiotherapy delays. CONCLUSION: This study was conducted on the basis of a pilot study that demonstrated the BCoG lozenge to be tolerable and microbiologically efficacious. A validated mucositis scoring system was used. However, in this group of patients treated with conventional radiotherapy, the lozenge did not impact significantly on the severity of mucositis. Whether such a lozenge would be beneficial in treatment situations where rate of severe mucositis is higher (ie, in patients treated with unconventional fractionation or with concomitant chemotherapy) is unknown.

Administration, Oral↗
PubMed2001

Multiple myeloma disrupts the TRANCE/ osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression.

Bone destruction, caused by aberrant production and activation of osteoclasts, is a prominent feature of multiple myeloma. We demonstrate that myeloma stimulates osteoclastogenesis by triggering a coordinated increase in the tumor necrosis factor-related activation-induced cytokine (TRANCE) and decrease in its decoy receptor, osteoprotegerin (OPG). Immunohistochemistry and in situ hybridization studies of bone marrow specimens indicate that in vivo, deregulation of the TRANCE-OPG cytokine axis occurs in myeloma, but not in the limited plasma cell disorder monoclonal gammopathy of unknown significance or in nonmyeloma hematologic malignancies. In coculture, myeloma cell lines stimulate expression of TRANCE and inhibit expression of OPG by stromal cells. Osteoclastogenesis, the functional consequence of increased TRANCE expression, is counteracted by addition of a recombinant TRANCE inhibitor, RANK-Fc, to marrow/myeloma cocultures. Myeloma-stroma interaction also has been postulated to support progression of the malignant clone. In the SCID-hu murine model of human myeloma, administration of RANK-Fc both prevents myeloma-induced bone destruction and interferes with myeloma progression. Our data identify TRANCE and OPG as key cytokines whose deregulation promotes bone destruction and supports myeloma growth.

Acid Phosphatase↗
PubMed2001

Induction of CD4(+) T cell-dependent CD8(+) type 1 responses in humans by a malaria DNA vaccine.

We assessed immunogenicity of a malaria DNA vaccine administered by needle i.m. or needleless jet injection [i.m. or i.m./intradermally (i.d.)] in 14 volunteers. Antigen-specific IFN-gamma responses were detected by enzyme-linked immunospot (ELISPOT) assays in all subjects to multiple 9- to 23-aa peptides containing class I and/or class II restricted epitopes, and were dependent on both CD8(+) and CD4(+) T cells. Overall, frequency of response was significantly greater after i.m. jet injection. CD8(+)-dependent cytotoxic T lymphocytes (CTL) were detected in 8/14 volunteers. Demonstration in humans of elicitation of the class I restricted IFN-gamma responses we believe necessary for protection against the liver stage of malaria parasites brings us closer to an effective malaria vaccine.

Adolescent↗
PubMed2001

Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients.

This report of a phase 2 trial of thalidomide (THAL) (200 mg/d; 200 mg increment every 2 weeks to 800 mg) for 169 patients with advanced myeloma (MM) (abnormal cytogenetics (CG), 67%; prior autotransplant, 76%) extends earlier results in 84 patients. A 25% myeloma protein reduction was obtained in 37% of patients (50% reduction in 30% of patients; near-complete or complete remission in 14%) and was more frequent with low plasma cell labeling index (PCLI) (below 0.5%) and normal CG. Two-year event-free and overall survival rates were 20% +/- 6% and 48% +/- 6%, respectively, and these were superior with normal CG, PCLI of less than 0.5%, and beta(2)-microglobulin of 3 mg/L. Response rates were higher and survival was longer especially in high-risk patients given more than 42 g THAL in 3 months (median cumulative dose) (landmark analysis); this supports a THAL dose-response effect in advanced MM.

Angiogenesis Inhibitors↗
PubMed2001

Increased genetic damage in oral leukoplakia from high risk sites: potential impact on staging and clinical management.

BACKGROUND: Two staging systems for oral leukoplakias have been proposed to better predict prognosis. Although one system includes site as an independent determinant, its use is controversial. METHODS: Recent studies have shown that loss of heterozygosity (LOH) in oral premalignancies is associated with risk of progression. The authors analyzed 127 oral dysplasias for LOH on 3 chromosome arms (3p, 9p, and 17p). The lesions included 71 from the floor of mouth, ventrolateral tongue, and soft palate complex (designated high risk [HR] sites) and 56 from the rest of the oral cavity (low risk [LR] sites). RESULTS: Dysplasias from HR sites contained significantly higher LOH frequencies than LR sites (percentage with any loss, P = 0.0004; percentage with multiple losses, P = 0.0001; percentage loss on each of the arms, P < 0.05). Loss on 3p and/or 9p, a pattern associated with a 24-fold increased risk of progression (Rosin MP, Cheng X, Poh C, Lam WL, Huang Y, Lovas J, et al. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res 2000;6:357-62) was more frequent among HR lesions (P = 0.0005). Loss of heterozygosity frequencies were elevated at HR sites among both genders and among smokers and nonsmokers. For different histologic groups, LOH frequencies were elevated for HR sites in mild dysplasias (P < 0.05) and moderate dysplasias (marginal significance, P = 0.06), but not in severe dysplasias/carcinoma in situ. CONCLUSIONS: Anatomic location of mild and moderate oral dysplasias in Western populations may be an important diagnostic indicator because lesions at HR sites have a greater tendency to include genetic alterations associated with elevated risk of progression.

Adult↗
PubMed2001

Neurocognitive evidence favors "top down" over "bottom up" mechanisms in the pathogenesis of body size distortions in anorexia nervosa.

Perceptually-based disturbances in body image, or body size distortions, have been posited to occur in anorexia nervosa (AN). Perception does not result from a simple flow of sensory information from periphery to cortex ("bottom-up" processing), but involves the selection of inputs most likely to be relevant in light of an individual's experience and expectations ("top-down" processing). Most investigations of body size distortion in AN have used procedures likely to engage top-down processing, raising the possibility that attitudinal disturbances may play a role. To our knowledge, there have been no studies that assess the presence, in AN, of neurocognitive deficits associated with neurologically based disturbances in body schema. Such deficits, if found, could provide evidence of body image distortion unlikely to result from top-down processing. We tested 20 inpatients with AN on measures of proprioception, finger identification, right/left orientation, general cognition and eating disorders symptomatology, both before and after treatment. Matched normal controls were tested on the same measures over the same time intervals. Significant differences between the two groups occurred only prior to treatment, and only on those measures which involved executive, in addition to more body-schema-specific functions. This suggests that patients with AN do not have enduring deficits in the domain of body-schema, but may have subtle cognitive dysfunction, in the acute state, which is not specific to, but can interact with processing of body-schema-related information. This, in turn, suggests that their body image distortion may not be secondary to bottom-up perceptual disturbances.

Adolescent↗
PubMed2001

A high frequency of allelic loss in oral verrucous lesions may explain malignant risk.

Verrucous carcinoma (VC), a variant of squamous cell carcinoma (SCC), is distinct from SCC in morphology and behavior. The underlying genetic changes involved in the development of VC and its precursor verrucous hyperplasia (VH) are unknown. This study determined whether chromosomal regions frequently lost during the development of SCC are also lost in the VH/VC variant. Twenty-five VH and 17 VC were analyzed for loss of heterozygosity (LOH) at 19 loci on 7 chromosome arms using microsatellite analysis. These data were compared with those from 47 reactive hyperplasias, 92 dysplasias (54 low- and 38 high-grade), and 41 SCCS: The results showed that VC/VH shared many of the losses present in dysplasia/SCC but differed in two aspects. First, VC/VH showed early acquisition of loss, compared with a gradual accumulation of losses from dysplasias to SCC. The LOH pattern of VH was similar to that of high-grade dysplasia and sharply different from reactive hyperplasia. The loss in VH often involved multiple arms (in 60% of VH vs 0% of reactive lesions). Only a marginal elevation of loss was observed at 9p (p = 0.06) and 4q (p = 0.05) from VH to VC because of the high degree of loss already present in VH. Second, a strikingly lower frequency of loss at 17p was noted in VH/VC compared with dysplasia/SCC and may indicate human papillomavirus (HPV) involvement. The finding of high-risk LOH profiles in VH may partly account for the high-progression risk seen for VH and also has potentially important clinical implications. The difficult pathological diagnosis of VH/VC from reactive hyperplasia frequently requires repeated biopsies and results in delay in diagnosis and significantly increased mortality/morbidity. Microsatellite analysis might facilitate this differential diagnosis.

Aged↗
PubMed2001

Selective COX-2 inhibitors: a review of their therapeutic potential and safety in dentistry.

Anti-inflammatory analgesics are commonly used medications in dental and medical practice. Their uses in dentistry include use as analgesics and as anti-inflammatory agents. In addition, antipyretic action accompanies the medication. The action of these groups of drugs depends on the dose provided. Analgesic and antipyretic effects occur at low dose, whereas analgesic effects occur at high dose. Among the common side effects of this class of medications are gastrointestinal irritation with potential for ulceration, increased tendency for bleeding due to antiplatelet effects, and long-term chronic dosing effects on renal function may occur. Recent developments in the anti-inflammatory group of medications include the introduction of cyclooxygenase-II inhibitors. These agents offer potentially significant advantages because of their relative lack of gastrointestinal irritation. Because of this, it is likely that these medications will be frequently used in the management of dental and medical conditions. Patients will present while on these medications, and these agents may serve as medications for management of dental pain, postsurgical pain, and for anti-inflammatory effects. The current literature indicates that COX-2 inhibitors offer substantial benefits because of their favorable gastrointestinal profiles and because of their lack of effect on platelet function.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

The LN54 radiation hybrid map of zebrafish expressed sequences.

To increase the density of a gene map of the zebrafish, Danio rerio, we have placed 3119 expressed sequence tags (ESTs) and cDNA sequences on the LN54 radiation hybrid (RH) panel. The ESTs and genes mapped here join 748 SSLp markers and 459 previously mapped genes and ESTs, bringing the total number of markers on the LN54 RH panel to 4226. Addition of these new markers brings the total LN54 map size to 14,372 cR, with 118 kb/cR. The distribution of ESTs according to linkage groups shows relatively little variation (minimum, 73; maximum, 201). This observation, combined with a relatively uniform size for zebrafish chromosomes, as previously indicated by karyotyping, indicates that there are no especially gene-rich or gene-poor chromosomes in this species. We developed an algorithm to provide a semiautomatic method for the selection of additional framework markers for the LN54 map. This algorithm increased the total number of framework markers to 1150 and permitted the mapping of a high percentage of sequences that could not be placed on a previous version of the LN54 map. The increased concentration of expressed sequences on the LN54 map of the zebrafish genome will facilitate the molecular characterization of mutations in this species.

Animals↗
PubMed2001

A description of inappropriate hospital stays in selected in-patient services: a study of cases receiving social work services.

The number of discharges (63,303) from a university-affiliated medical center in Israel were reviewed. Eight percent of cases in three departments rcceivcd social work services. Patients experiencing inappropriate hospital stay (discharge delay) and who received social work services were characterized and compared with social work clients not experiencing delay. Discharge delay patients differed from other social work clients on key sociodemographic variables. Patients admitted because of "injury" were significantly more likely to experience delay than patients admitted because of "illness." "Waiting for community/institutional resources" was the most common reason for delay and discharge to an institutional setting increased the likelihood of delayed discharge. High risk factors were department-specific and should be studied in context. Results suggested the limited but positive impact of hospital-community collaborative strategies in reducing the incidence of delay over time.

Adult↗
PubMed2000

Increased anterior cingulate and caudate activity in bipolar mania.

BACKGROUND: Executive control of cognition, emotion, and behavior are disrupted in the manic state of bipolar disorder. Whereas frontal systems are implicated in such dysfunction, the localization of functional brain abnormalities in the manic state is not well understood. METHODS: We utilized a high-sensitivity H(2)(15)0 positron emission tomography technique to investigate regions of increased brain activity in mania, compared to euthymia, in bipolar disorder. RESULTS: The principal findings were manic state-related increased activity in left dorsal anterior cingulate, and left head of caudate. CONCLUSIONS: The findings suggest that the manic state of bipolar disorder may be associated with heightened activity in a frontal cortical-subcortical neural system that includes the anterior cingulate and caudate.

Adult↗