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Biomedical subjects

A Rosen

Publications and source records attributed to A Rosen.

At least 37 records · Page 2Linked to original sources
PubMed2001

The role of laparoscopic ultrasound in the minimally invasive management of symptomatic hepatic cysts.

BACKGROUND: Now that the laparoscopic treatment of symptomatic liver cystic disease has proven feasible and safe, it is gaining wide acceptance. However, due to diagnostic pitfalls and a relatively high recurrence rate, further improvements and refinement of the procedure are still needed. We have evaluated the contribution of laparoscopic ultrasound in the diagnosis and management of patients with symptomatic liver cysts. METHODS: Twelve patients with single or multiple cysts of the liver and two patients with polycystic liver disease were managed laparoscopically. Laparoscopic ultrasound served as an integral part of the procedure in all patients. RESULTS: Patients underwent either complete cyst excision (two cases) or resection of the extrahepatic cystic component (eight cases). Additionally, in two patients, deep cysts not demonstrated by preoperative imaging studies were detected and treated with a combination of laparoscopy and laparoscopic ultrasound. In one patient with a cystobiliary fistula, conversion to an open cystjejunostomy was necessary. Patients with polycystic liver disease underwent a combination of excision and unroofing of both superficial and deeper cysts using laparoscopic contact ultrasound throughout the procedure. Laparoscopic ultrasonography was found to have a significant impact on the operative strategy in five patients (36%) with multiple cysts or polycystic disease. The postoperative course was uneventful in all cases. Thirteen patients remained asymptomatic throughout the follow-up period of 30 months; one patient with polycystic liver disease developed recurrent symptoms after 5 months and was treated with left hepatectomy. CONCLUSION: Additional use of laparoscopic ultrasound enables the detection, differentiation, and treatment of deep, nonvisualized cystic lesions (two patients, 16.6%) and validation of the adequacy of the laparoscopic procedure.

Adult↗
PubMed2001

Prediction of aspiration in patients with newly diagnosed untreated advanced head and neck cancer.

OBJECTIVES: To determine the prevalence of aspiration in patients with newly diagnosed nontreated advanced head and neck cancer and to determine the ability of the clinical examination to predict aspiration in this patient population. DESIGN: A descriptive prevalence study of the presence of aspiration in patients with advanced (stages III and IV) head and neck cancer and a prospective correlation study between variables of the clinical evaluation with the criterion standard videofluoroscopy. SETTING: Regional veterans affairs medical center. PATIENTS: A consecutive sample of 27 patients without previous treatment or tracheostomy. INTERVENTIONS: All patients underwent evaluation by an otolaryngologist and speech pathologist prior to videofluoroscopy. MAIN OUTCOME MEASURES: Variables in the dysphagia evaluation (consisting of a directed medical history, physical examination, and food challenge), the self-rated 45-item questionnaire, and the clinicians "educated prediction" of aspiration were analyzed with reference to aspiration on videofluoroscopy using univariant analysis. RESULTS: The prevalence of aspiration determined by videofluoroscopy was 41% (11 of 27 patients). Two (6%) of 32 items in the medical history, 1 (4%) of 25 items in the physical examination, and 8 (50%) of 16 items in the food challenge were found to be statistically significantly correlated (P<.05) with aspiration on videofluoroscopy by univariate analysis. Nine (25%) of 45 items in the self-rated questionnaire were correlated with aspiration on videofluoroscopy. The clinicians' educated prediction of aspiration was not correlated with aspiration determined by videofluoroscopy. CONCLUSIONS: Clinical evaluation alone is inadequate in predicting patients who aspirated, determined objectively by videofluoroscopic swallowing study. Further study is needed to develop an efficient dysphagia evaluation to identify patients at risk for aspiration.

Aged↗
PubMed2001

The DNA mismatch repair enzyme PMS1 is a myositis-specific autoantigen.

OBJECTIVE: The specificity of the autoantibody response in different autoimmune diseases makes autoantibodies useful for diagnostic purposes. It also focuses attention on tissue- and event-specific circumstances that may select unique molecules for an autoimmune response in specific diseases. Defining additional phenotype-specific autoantibodies may identify such circumstances. This study was undertaken to investigate the disease specificity of PMS1, an autoantigen previously identified in some sera from patients with myositis. METHODS: We used immunoprecipitation analysis to determine the frequency of autoantibodies to PMS1 in sera from patients with myositis, systemic lupus erythematosus, or scleroderma and from healthy controls. Additional antigens recognized by PMS1-positive sera were further characterized in terms of their susceptibility to cleavage by apoptotic proteases. RESULTS: PMS1, a DNA mismatch repair enzyme, was identified as a myositis-specific autoantigen. Autoantibodies to PMS1 were found in 4 of 53 patients with autoimmune myositis (7.5%), but in no sera from 94 patients with other systemic autoimmune diseases (P = 0.016). Additional mismatch repair enzymes (PMS2, MLH1) were targeted, apparently independently. Sera recognizing PMS1 also recognized several other proteins involved in DNA repair and remodeling, including poly(ADP-ribose) polymerase, DNA-dependent protein kinase, and Mi-2. All of these autoantigens were efficiently cleaved by granzyme B, generating unique fragments not observed during other forms of cell death. CONCLUSION: PMS1 autoantibodies are myositis specific. The striking correlation between an immune response to a group of granzyme B substrates (functioning in DNA repair and remodeling) and the myositis phenotype strongly implies that tissue- and event-specific biochemical events play a role in selecting these molecules for an autoimmune response. Understanding the role of granzyme B cleavage in this response is an important priority.

Adult↗
PubMed2001

Novel fragments of the Sjögren's syndrome autoantigens alpha-fodrin and type 3 muscarinic acetylcholine receptor generated during cytotoxic lymphocyte granule-induced cell death.

OBJECTIVE: To determine whether the Sjögren's syndrome autoantigens alpha-fodrin and the type 3 muscarinic acetylcholine receptor (M3R) are cleaved during cytotoxic lymphocyte granule-induced death, to yield novel fragments. METHODS: Primary salivary gland epithelial cells, human salivary gland cells, and HeLa cells were incubated with granule contents. The susceptibility to cleavage and the generation of novel fragments of Sjögren's syndrome autoantigens in this form of apoptosis was assessed by immunoblotting. Cleavage of M3R was further characterized by assays performed on the M3R molecule generated by in vitro translation. RESULTS: This study demonstrated that alpha-fodrin was uniquely cleaved during cytotoxic lymphocyte granule-induced cell death, generating a 155-kd fragment distinct from those generated by caspase 3 in other forms of apoptosis. The study also demonstrates that M3R (which is restricted in expression to the peripheral autonomic organs) was efficiently cleaved by granzyme B (but not by caspases) at several sites, both in vitro and in intact cells. This is the first description of cleavage of a transmembrane autoantigen by granzyme B. CONCLUSION: The observation that both ubiquitously expressed autoantigens (e.g., alpha-fodrin, La, and nuclear mitotic apparatus protein) and tissue-restricted autoantigens (e.g., M3R) targeted in Sjögren's syndrome are specifically cleaved by granzyme B, generating unique fragments, strongly suggests that a common biochemical event (novel autoantigen cleavage during granule-induced epithelial cell death) is responsible for selecting this apparently unconnected group of molecules for a high-titer autoantibody response. The data focus attention on the role of cytotoxic lymphocytes in the initiation and propagation of Sjögren's syndrome.

Animals↗
PubMed2001

Adenovirus L4-100K assembly protein is a granzyme B substrate that potently inhibits granzyme B-mediated cell death.

Cytotoxic lymphocytes kill virus-infected target cells and play a critical role in host recovery from viral infections. Granzyme B (GrB) is a cytotoxic lymphocyte granule protease that plays a critical role in mediating cytotoxicity. In these studies, we demonstrate that the adenovirus assembly protein L4--100K (100K) is a GrB substrate that prevents cytotoxic lymphocyte granule-induced apoptosis in infected target cells by potently inhibiting GrB. This inhibition is absolutely dependent on Asp-48 in 100K, found within a classic GrB consensus motif. 100K is the first viral protein described that exclusively targets the GrB pathway. It represents a novel class of viral protease inhibitor, in which an essential, multifunctional viral protein, which is vulnerable to specific proteolysis by GrB, expresses inhibitory function against that protease.

Adenoviruses, Human↗
PubMed2001

Moving out and moving on: some ethnographic observations of deinstitutionalization in an Australian community.

Since the 1950s deinstitutionalization has taken place for people with mental illnesses in the Western world. The growth of community care and residential facilities, as well as planning and implementation of policies, has varied in timing and orientation. An appreciation of the process of change affecting people discharged to the community highlights their strength, resilience, and vulnerabilities. This paper outlines a two and a half year ethnographic qualitative study undertaken in Australia, where 47 long-stay psychiatric inpatients were discharged to the community. The process accompanied the amalgamation of two major psychiatric hospitals, resulting in the closure of one. Findings demonstrated slow but positive change for residents as they reintegrated into the community. A separate quantitative and economic study was undertaken alongside the qualitative study (for results see Hobbs, et al., 2000; Newton, et al, 2000; Lapsley, et al., 2000).

Adult↗
PubMed2001

Does case management work? The evidence and the abuse of evidence-based medicine.

OBJECTIVES: This study reviews typologies of psychiatric case management and then discusses the efficacy, effectiveness and cost effectiveness of psychiatric case management, with particular focus on evidence from Australia and the UK. Subsequently, it aims to examine the way such evidence has been interpreted in the context of UK psychiatric research and services. Finally it examines the ways in which, by the selective reviewing or editorializing of evidence, case management has been brought into disrepute in the UK. METHOD: This study reviews literature of the recent evidence for case management, and asks three questions of case management: has it been shown to be efficacious in controlled research, is it effective in applied settings, and is it cost effective? An examination is then made of the concurrent representations of the UK evidence in both the academic literature and the media. RESULTS: There is strong evidence for the efficacy effectiveness and cost-effectiveness of case management in psychiatry, the closer it conforms to active and assertive community treatment models. It appears, however, that studies and evidence-based reviews of case management have possibly been misused and misrepresented in a highly charged atmosphere of professional media debate. The potential for this abuse is not limited to psychiatry and remains a challenge for all evidence-based practice. CONCLUSION: On the evidence, assertive community treatment case management is one of the most effective interventions in psychiatry today. Despite improving the evidence base for practice (e.g. as has occurred for case-management in psychiatry), evidence-based medicine (EBM) is still susceptible to compromise and misrepresentation, due to unexamined or undeclared bias. Unless this potential for abuse is recognized and checked, EBM in psychiatry is in danger of being discredited at the hand of some of its own proponents. There is a need for more rigorous pursuit of evidence-based psychiatry, including more systematic declaration of bias in all research, whether quantitative or qualitative in design.

Australia↗
PubMed2001

Development of a brief form of the Life Skills Profile: the LSP-20.

OBJECTIVE: To develop a brief form of the Life Skills Profile (LSP) that incorporates all five subscales of the full form. METHOD: A new short form of the LSP (LSP-20) was developed to incorporate all five subscales of the full form. The LSP-20 development was based on a reanalysis of data from previously published studies. These data sets were also reanalysed to determine any differential effects of numbers and percentages of items in the LSP-39, LSP-16 and LSP-20, comparability of scores of the different forms, of test-retest and interrater reliability, and validity of the LSP-20 by comparison with the Positive and Negative Syndrome Scale (PANSS). RESULTS: A twenty-item short form of the LSP-39 (LSP-20) is described which retains 16 items of an earlier short form but which also reproduces the subscale concerned with disability associated with positive psychotic phenomena. The subscales correlated highly with their counterparts in the full form, interrater and test-retest reliabilities were comparable, and concurrent validity was good. CONCLUSIONS: The LSP-20 is a brief form of a widely used instrument that offers equivalent coverage to the full form with sound empirical properties, though unlike the LSP-39, it can be scored in the direction of impairments or strengths. Therefore the LSP-20 may be more suited to routine service disability and aggregated outcome assessments, but less suited than the LSP-39 to detailed research, or to interactive use as part of service user's individual care planning and review.

Adult↗
PubMed2001

Bcl-2-dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis.

The close association between autoantibodies against pyruvate dehydrogenase-E2 (PDC-E2), a ubiquitous mitochondrial protein, and primary biliary cirrhosis (PBC) is unexplained. Many autoantigens are selectively modified during apoptosis, which has focused attention on apoptotic cells as a potential source of "neo-antigens" responsible for activating autoreactive lymphocytes. Since increased apoptosis of bile duct epithelial cells (cholangiocytes) is evident in patients with PBC, we evaluated the effect of apoptosis on PDC-E2. Autoantibody recognition of PDC-E2 by immunofluorescence persisted in apoptotic cholangiocytes and appeared unchanged by immunoblot analysis. PDC-E2 was neither cleaved by caspases nor concentrated into surface blebs in apoptotic cells. In other cell types, autoantibody recognition of PDC-E2, as assessed by immunofluorescence, was abrogated after apoptosis, although expression levels of PDC-E2 appeared unchanged when examined by immunoblot analysis. Both overexpression of Bcl-2 and depletion of glutathione before inducing apoptosis prevented this loss of autoantibody recognition, suggesting that glutathiolation, rather than degradation or loss, of PDC-E2 was responsible for the loss of immunofluorescence signal. We postulate that apoptotic cholangiocytes, unlike other apoptotic cell types, are a potential source of immunogenic PDC-E2 in patients with PBC.

Apoptosis↗
PubMed2001

Rhinoscleroma mimicking nasal polyposis.

Rhinoscleroma is increasing in incidence in the United States. It should be considered in patients who are immigrants from endemic countries and present with nasal polyposis that exhibits significant adherence to the nasal septum and relative sparing of the sinuses. Fluoroquinolones are emerging as the adjunctive antibiotic treatment of choice to complement surgical extirpation of the disease.

Adult↗
PubMed2001

Bone conduction impairment in chronic ear disease.

The preoperative and postoperative bone conduction (BC) thresholds were prospectively investigated in 24 patients with chronic ear disease in the form of cholesteatoma, chronic suppurative otitis media, or adhesive otitis media. All underwent tympanoplasty with mastoidectomy. Ossicular reconstruction was performed in 14, and the remaining 10 were still awaiting second-stage ossicular reconstruction at the time of this investigation. In each group, the postoperative results were compared with the preoperative results by the paired-samples t-test. In the ossicular reconstruction group, the results revealed a significant improvement in the postoperative BC thresholds, as compared with the preoperative BC thresholds, at 250, 1,000, and 2,000 Hz, with the largest mean improvement observed at 2,000 Hz. No significant improvement was observed at any frequency for the group without ossicular reconstruction. Postoperative improvement of at least 10 dB at 2 or more frequencies was observed in 71% of the ossicular reconstruction group, as compared with 0% of the group that did not undergo ossicular reconstruction. The results support the theory that the elevated BC thresholds of patients with chronic ear disease result from the elimination, due to disease, of the middle ear contribution (from the inertial ossicular component and ossicular resonance) to the BC response. The results also suggest that the middle ear contribution to the BC response is restored with ossicular reconstruction.

Adult↗
PubMed2001

[Aggressive surgical treatment for cholangiocarcinoma].

Surgery remains the only curative approach to cholangiocarcinoma. Despite operative difficulties concerning tumor location, vascular involvement or hepatic invasion curative resection (i.e. achievement of tumor free margins) carries good survival rates and is associated with low morbidity and mortality. Our experience with 31 patients with cholangiocarcinoma operated during the years 1993-1999 is presented. Twenty-five patients were found to have hilar cholangiocarcinoma, 3 carcinoma of mid-choledochus and 3 distal cholangiocarcinoma. All patients were evaluated by a diagnostic protocol including laparoscopy and laparoscopic ultrasound. Surgery consisted of local resection of the tumor with Roux en Y hepaticojejunostomy reconstruction. Three patients had concomitant hepatic resection for hilar cholangiocarcinoma while 3 patients had pancreaticoduodenectomy for distal cholangiocarcinoma. Adenocarcinoma was diagnosed in all patients. Curative resection was achieved in 19 patients and palliative resection (microscopically involved resected margins) in 12. One patient died at 60 days postop (3.5% mortality). Postoperative complications included cholangitis occurring in 10 patients who were referred with biliary drains, intraabdominal abscess (2 patients) and biliary leakage (1 patient) all treated conservatively. Overall survival rate was 82% at one year, 73% at two years and 45% at 5 years. When comparing curative resection with palliative resection, survival rates were 92% versus 71% for 1 year, 72% versus 50% for 2 year and 57% versus 14% for 5 years. Selection of patients using Laparoscopic Ultrasound combined with aggressive surgical approach enable curative or palliative resection 15 the only treatment modality which is significantly improved survival.

Adult↗
PubMed2000

Donor bone marrow-derived chimeric cells present in renal transplant recipients infused with donor marrow. I. Potent regulators of recipient antidonor immune responses.

BACKGROUND: Even though a number of transplant centers have adopted donor-specific bone marrow cell (DBMC) infusions to enhance donor cell chimerism, to date there has been no direct evidence linking chimerism with tolerance induction in human organ transplant recipients. METHODS: Cells of donor phenotype were isolated 1 year postoperatively from the peripheral blood lymphocytes and iliac crest bone marrow of 11 living-related-donor (LRD) renal transplant recipients, who had received perioperative donor bone marrow cell infusions. These recipient-derived donor (RdD) cells were characterized phenotypically by flow cytometric analysis and functionally as modulators in mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. RESULTS: The yield of RdD cells ranged from 0.1 to O.9% of the starting material with the majority being TcRalphabeta, CD3 positive T cells, a substantial percentage of which coexpressed CD28. At 1 year posttransplant almost 50% of the LRD-kidney/DBMC recipients tested so far exhibited donor-specific unresponsiveness in MLR (7/17) and CML (6/13) reactions and this trend was further enhanced at 23 years. In the recipients with residual positive antidonor immune responses, the RdD cells inhibited recipient antidonor MLR and CML responses significantly more strongly than freshly isolated and similarly treated iliac crest bone marrow cells from the donor. RdD cells also inhibited the MLR of the recipient to third party allogeneic stimulator cells; however, this nonspecific effect was significantly weaker than specific inhibition. We also established long-term bone marrow cultures stimulated every 2 weeks with irradiated alogeneic feeder cells, that had similar functional properties thus possibly providing us with an in vitro correlate the RdD cells. CONCLUSIONS: These results clearly support the notion that the infused donor cells play a positive role in the induction and/or maintenance of transplant tolerance.

Bone Marrow Transplantation↗
PubMed2000

The relevance of adjuvant therapy in primary carcinoma of the fallopian tube, stages I and II: irradiation vs. chemotherapy.

INTRODUCTION: Primary carcinoma of the Fallopian tube (FTC) is a rare but extremely aggressive neoplasm. It must be expected to cause up to 40% of tumor-related deaths even in Stage I, and up to 57% in Stage II. Due to its rarity, there exist only a few and divergent reports on the value of adjuvant therapy. Therefore the present study aims at evaluating the influence of postoperative adjuvant therapy on FTC by studying the effects of irradiation and chemotherapy on the overall survival of patients in Stages I and II. PATIENTS AND METHODS: We investigated 95 cases of FTC in Stages I (n = 66) and II (n = 29) in a retrospective multicenter study. Group I (n = 32) are patients who underwent a complete irradiation with cobalt or photon energies of 23 MV (administering a daily dose of 2 Gy resulted in a total of 45-52 Gy in the pelvic areas). Group II (n = 31) consists of those cases who received postoperative chemotherapy with platinum. Thirty-two women were excluded from this study because they had other chemotherapies, incomplete irradiation, or no adjuvant therapy at all. RESULTS: Median survival time was 57 months in Group I patients (95% confidence interval 33-81 months), compared to 73 months (95% confidence interval, 68-78 months) in the chemotherapeutically treated Group II. This difference did not prove to be statistically significant (p = 0.476).If primary surgical therapy is included in the evaluation, and patients with total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) are compared to those with additional radical lymphadenectomy (TAH+BSO+lymph nodes), the latter group's overall survival essentially improves but fails to reach statistical significance. Their 5-year survival rate is 83% against 58% in the TAH+BSO group (p = 0.12). CONCLUSION: Chemotherapy and irradiation are two adjuvant therapies that are similarly effective in FTC of Stages I and II, with chemotherapy being preferred at the present time. Primary surgical treatment, however, is of crucial impact on the prognosis of FTC.

Antineoplastic Agents↗
PubMed2000

(-)-Spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha 7 nicotinic acetylcholine receptor.

Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha 7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2. 2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha 7 nicotinic receptor, which is highly selective for the rat alpha 7 nicotinic receptor over the alpha 4 beta 2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha 7 nicotinic receptor affinity.

Acetylcholine↗