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Biomedical subjects

B J Cohen

Publications and source records attributed to B J Cohen.

At least 55 records · Page 3Linked to original sources

B19 parvovirus infection in children with malignant solid tumors receiving chemotherapy.

Two children with rhabdomyosarcoma developed severe anemia following chemotherapy; anemia was more severe compared to that observed following earlier chemotherapy cycles. While one patient had a brisk reticulocytosis, the other had no demonstrable reticulocytes. Both patients had evidence of acute B19 parovirus infection and subsequently developed appropriate antibody response. A diagnosis of B19 parvovirus infection should be considered in any patient who develops persistent or severe anemia while on chemotherapy.

Acute Disease↗

How do physicians weigh iatrogenic complications?

OBJECTIVE: To determine how physicians weigh iatrogenic complications when making clinical decisions. DESIGN: Physicians were mailed a questionnaire describing two simplified scenarios--one involving a patient with a cerebral embolism and the other involving a patient with a life-threatening arrhythmia. In each scenario there was one potential natural adverse outcome (which could be prevented with drug therapy) and one potential drug side effect (iatrogenic adverse outcome), which would be clinically indistinguishable from the natural adverse outcome. Half the respondents were given the probability of the natural adverse outcome (PN) and were asked to specify the probability of the iatrogenic adverse outcome (PI) at which they felt that giving and withholding the therapy were equivalent strategies. The other respondents were given the PI and asked to specify the PN at which they felt the two strategies were equivalent. SETTING: Academic medical center. PARTICIPANTS: Staff physicians. MEASUREMENTS AND MAIN RESULTS: Results are expressed as the ratio PI/PN at which the respondent felt that giving and not giving therapy were equivalent strategies. A ratio less than 1 indicates that errors of commission (iatrogenic adverse outcomes) were given more weight than were errors of omission (natural adverse outcomes when therapy was withheld). Ratios less than 1 were provided in 56% of the responses (n = 230). The mean PI/PN in the group with ratios less than 1 was 0.53 +/- 0.26 (SD; n = 129). CONCLUSIONS: In making decisions, some physicians appear to weigh errors of commission more heavily than they do errors of omission, while others weigh them equally. This diversity of physicians' attitudes may explain some of the variation observed in clinical practice in settings where The possibility of iatrogenic complications is of concern.

Anti-Arrhythmia Agents↗

IgM antibody capture haemadherence test (MACHAT) for the detection of measles specific IgM.

An antibody capture haemadherence test (MACHAT) for detecting measles-specific IgM is described. The assay is based on the antibody capture principle with rhesus monkey erythrocytes as detector system in place of labelled antisera. MACHAT was compared with a commercial indirect enzyme immunoassay (EIA) for measles-specific IgM using 382 sera from patients notified as measles. There was good agreement between the two tests; 106 sera were found to contain measles IgM by both tests, 7 further sera were positive only in the commercial EIA and 9 only in MACHAT. One sera gave an equivocal result in MACHAT and another in the commercial EIA. Twelve of the 18 sera with discrepant results were also tested by MACRIA; in 7 MACRIA gave the same results as MACHAT, in 3 the MACRIA results agreed with the commercial test and in 2 the MACRIA results were equivocal. Specificity was established by a lack of MACHAT reactivity in sera collected from blood donors (n = 83) and from cases of recent rubella, dengue and parvovirus B19 infection (n = 51). The MACHAT is a simple, cheap test that can be read by eye and is suitable for measles surveillance programmes in the developing world.

Hemadsorption Inhibition Tests↗

Parvovirus B19 outbreak on an adult ward.

In November and December 1992, an outbreak of parvovirus B19 infection occurred among patients and staff on an adult mixed surgical ward at a large hospital in London. Three patients and 15 staff members were serologically confirmed as acute cases. The attack rate among susceptible members of staff was 47%. In those infected, arthralgia (80%) and rash (67%) were the most common symptoms. Of six susceptible in-patients on the ward, three became infected. One of the in-patients who had carcinoma of the mouth was viraemic for more than 10 days with marrow suppression resulting in the postponement of chemotherapy until intravenous immunoglobulin was given and he was no longer viraemic. Control measures taken included closure of the ward to new admissions, transfer of only immune staff to the ward, and restriction of the ward nursing staff to working only on that ward. Although no specific exposure was conclusively identified as a risk factor, there was a suggestion of an increased risk of acquiring parvovirus B19 infection among those staff who did not adopt strict hand washing procedures after each physical contact with a patient (RR = 2.33; P = 0.07). Knowledge of parvovirus B19 among interviewed health care workers was poor: only 42% reported knowing about parvovirus B19 and only 38% could name a patient category at risk of a severe outcome following infection. This is the first report of a nosocomial outbreak affecting an adult ward and of possible transmission of parvovirus B19 infection from staff to in-patients. Hospital control of infection teams should include parvovirus B19 in their outbreak containment plans.

Adult↗

Parvovirus B19 as a cause of acquired chronic pure red cell aplasia.

Parvovirus B19 infection causes chronic anaemia in immunodeficient individuals by selective suppression of erythropoiesis. The bone marrow morphology is characteristic of pure red cell aplasia (PRCA). To determine the frequency of B19-induced PRCA we retrospectively analysed a series of 57 PRCA patients. B19 DNA was present in serum of eight patients (14%) and could be extracted from bone marrow aspirate slides from five of these patients. Recent exposure to the virus was confirmed by the presence of anti-B19 IgM in sera from four and by the finding of giant pronormoblasts in marrow aspirates from five of the B19 DNA-positive patients. The sensitivities of anti-B19 IgM and of giant pronormoblasts were only 50% and 63%, respectively; specificities were 90% and 92%. Unexpectedly, PRCA in two B19 DNA-positive patients remitted after antilymphocyte globulin or cyclosporin A therapy, suggesting that the clinical course of B19-induced PRCA may be indistinguishable from other forms of PRCA. As therapy with immunoglobulin is uniformly effective for treatment of B19-associated anaemia, our data suggest that all patients with acquired PRCA should be evaluated for evidence of B19 infection. B19 DNA analysis is the most reliable method to demonstrate infection.

Adolescent↗

Application to immunoglobulin M capture hemadherence assays of hemagglutination of monkey erythrocytes by native and recombinant human parvovirus B19 antigens.

Human parvovirus B19 recently was shown to agglutinate baboon and human erythrocytes. We have now demonstrated that both recombinant and native B19 antigens agglutinate rhesus, cynomolgus, and Saimiri monkey erythrocytes. Using cynomolgus erythrocytes and the recombinant antigen, we developed an immunoglobulin M (IgM) antibody capture hemadherence test (MACHAT) for the detection of specific B19 IgM antibodies in human sera. The results obtained with MACHAT were compared with those obtained with an IgM capture enzyme immunoassay (MACEIA) employing the native antigen routinely used in our laboratory. For 229 patient serum samples, we found 96% agreement between the results of the two assays. There was some evidence that MACHAT was slightly more sensitive than MACEIA. Our results add to the range of erythrocytes that can be agglutinated by B19 virus and show that native as well as recombinant antigens may be used in MACHAT.

Animals↗

Personality disorder in later life: a community study.

BACKGROUND: This exploratory study compares the prevalence of personality disorders and traits in people over and under 55 years of age. The comorbidity between personality and other psychiatric disorders is also examined. METHOD: Psychiatrists examined 810 subjects in a two-stage community survey. The semi-structured Standardized Psychiatric Examination was used to diagnose all DSM-III personality disorders and other psychiatric disorders. RESULTS: The older subjects were significantly less likely than the younger subjects to have any personality disorder (6.6% v. 10.5%; relative odds = 0.42, 95% confidence interval = 0.25-0.70, P < 0.001). Antisocial and histrionic personality disorders were much less prevalent in the older than younger subjects (P < 0.05). The older subjects also had significantly fewer maladaptive personality traits (chi 2 = 88.9, d.f. = 3, P < 0.001). The patterns of comorbidity between personality disorders and other psychiatric disorders were different in the two age groups. CONCLUSIONS: It is important to evaluate personality in patients of all ages. While some older patients no longer meet criteria for personality disorder, maladaptive traits may become evident during times of stress.

Adolescent↗

Cost-effectiveness of a smoking cessation program after myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the cost-effectiveness of a smoking cessation program initiated after acute myocardial infarction. BACKGROUND: The value of allocating health care resources to smoking cessation programs after myocardial infarction has not been compared with the value of other currently accepted interventions. METHODS: A model was developed to examine the cost-effectiveness of a recently reported smoking cessation program after an acute myocardial infarction. The cost was estimated by considering the resources necessary to implement the program, and the effectiveness was expressed as discounted years of life saved. Years of life saved were estimated by modeling life expectancy using a single declining exponential approximation of life expectancy based on data from published reports. RESULTS: The cost-effectiveness of the nurse-managed smoking cessation program was estimated to be $220/year of life saved. In a one-way sensitivity analysis, the cost-effectiveness of the program remained < $20,000/year of life saved if the program decreased the smoking rate by only 3/1,000 smokers (baseline assumption 26/100 smokers), or if the program cost as much as $8,840/smoker (baseline assumption $100). In a two-way sensitivity analysis, even if the cost of the program were as high as $2,000/participant, the cost-effectiveness of the program would be < $10,000/year of life saved so long as the program helped an additional 12 smokers quit for every 100 enrolled. CONCLUSIONS: Over a wide range of estimates of costs and effectiveness, a nurse-managed smoking cessation program after acute myocardial infarction is an extremely cost-effective intervention. This program is more cost-effective than beta-adrenergic antagonist therapy after myocardial infarction.

Analysis of Variance↗

Parvovirus B19 as a cause of chronic anemia in rhabdomyosarcoma.

BACKGROUND: Several reports have been published of anemia due to infection by parvovirus in patients receiving chemotherapy for leukemia. However, parvovirus B19 has not been previously identified as a cause of chronic anemia in children with solid tumors. METHODS: A child with rhabdomyosarcoma developed chronic anemia, with need for regular blood transfusions during chemotherapy. An infectious etiology was sought. RESULTS: B19 viremia and an absent antibody response was present during the period of chronic anemia during chemotherapy. After completion of chemotherapy, the viremia cleared, IgM and IgG antibody to B19 virus were detected, and the anemia resolved. CONCLUSIONS: Parvovirus must be considered as a cause of anemia in patients undergoing chemotherapy for solid tumors as well as leukemia.

Anemia, Aplastic↗

Detection of human parvovirus B19-specific IgM and IgG antibodies using a recombinant viral VP1 antigen expressed in insect cells and estimation of time of infection by testing for antibody avidity.

Sera from patients with symptoms of recent human parvovirus B19 (B19) infection were tested for B19-specific IgM in an immunofluorescence assay (IFA) using insect cells expressing B19 recombinant VP1 coat protein as an antigen. A highly significant correlation (P < 0.001) was found between titres obtained in the IgM IFA and the units obtained in an IgM antibody-capture RIA using plasma derived native B19 antigen. An IgG IFA using the recombinant antigen was performed on 57 sera and the antibody avidity determined. There was a highly significant correlation (P < 0.001) between the relative amounts of low avidity B19-specific IgG antibodies and time after onset of illness. This finding allows the detection of IgG to be used for diagnosing acute infection.

Animals↗

Antibody capture haemadherence tests for parvovirus B19-specific IgM and IgG.

In the absence of serum inhibitor human parvovirus B19 agglutinates primate red cells. Agglutination of baboon erythrocytes by inhibitor free baculovirus expressed VP1/VP2 proteins of B19 virus was enhanced by low pH. To avoid interference from inhibitor(s) present in serum specimens microtitre tests with an antibody capture configuration were designed and optimised. Antigen binding was demonstrated by the adherence of baboon erythrocytes. These tests (MACHAT, GACHAT) detected IgM or IgG anti-B19 in 1032 serum specimens with an overall sensitivity of 99%, specificity of 98.2% and positive predictive value of 96.8% with reference to the radioimmunoassays currently in diagnostic use. MACHAT and GACHAT are straightforward, and well suited to large scale research and seroepidemiological investigations. They are without the risks from infectious antigen and radiation associated with existing radioimmunoassays and allow the phenomenon of B19 virus haemagglutination to be put to practical advantage.

Adolescent↗

Detection of parvovirus B19 in donated blood: a model system for screening by polymerase chain reaction.

A highly sensitive and rapid method for routinely screening large numbers of donated blood units for parvovirus B19 by the polymerase chain reaction (PCR) was developed. Over a 3-month trial period in Edinburgh, B19 DNA was detected in 6 of 20,000 consecutive units of blood (0.03%), in concentrations ranging from 2.4 x 10(4) to 5 x 10(10) copies of viral DNA per ml. Seroconversion for B19-specific immunoglobulin M and immunoglobulin G and disappearance of circulating B19 DNA occurred in the interval between donation and recall in four of the five implicated donors who could be recalled. B19 DNA was detected in 18 of 27 separate batches of non-heat-treated factor VIII and IX concentrate manufactured from donated plasma unscreened for B19 DNA. Dry-heat treatment at 80 degrees C for 72 h reduced but did not always eliminate detectable B19 from factor VIII concentrates, consistent with recent observations that current methods for virus inactivation during blood product manufacture are insufficient to entirely eliminate B19 infectivity. The methods developed in this study for PCR screening could be applied routinely to prevent transfusion of B19 in blood and blood products and could play an important role in the prevention of iatrogenic transmission of infection. PCR screening could also be used for detection and exclusion of a range of other transmission-associated viruses for which current serological detection methods are only partially effective.

Base Sequence↗

Use of recombinant human parvovirus B19 antigens in serological assays.

AIMS--To compare the sensitivity, specificity, and practicality of recombinant proteins in serological tests for the detection of human parvovirus B19 IgG and IgM. METHODS--Indirect enzyme linked immunosorbent assays using B19 structural proteins expressed in Escherichia coli were developed for the detection of B19 specific IgG and IgM (rELISA-G and rELISA-M). Cells infected with baculovirus expressing B19 structural proteins were also used in an indirect immunofluorescence assay for IgG and IgM antibodies (IFA-G and IFA-M). Antibody capture radioimmunoassays for IgG and IgM (GACRIA and MACRIA) were used as comparative assays. RESULTS--Twenty nine pools of intravenous immunoglobulin were clearly positive for B19 IgG by rELISA-G and contained low IgG titres by GACRIA. From 113 samples tested by all methods, sensitivities of 92% (77/84) and 97% (68/70) were obtained for ELISA and immunofluorescence, respectively, when compared with GACRIA. One hundred and sixteen samples from patients presenting with rash or arthralgia were compared by MACRIA, rELISA-M, and IFA-M. Sensitivities of both recombinant tests were more than 95%. Despite pretreatment to remove IgG or rheumatoid factor, false positive results were a problem in the rELISA-M but were not seen with the IFA-M. CONCLUSIONS--The limited supply of native antigen has severely restricted the wide application of serology for parvovirus B19. The use of recombinant antigens permitted the introduction of local screening tests which had many advantages, including quicker results and relief of the burden on the Reference Laboratory. The use of rELISA-M for sensitivity and IFA-M for specificity and confirmation proved a useful and practical combination for diagnosis of recent infection with B19, and rELISA-G allowed the immune response to be determined in selected populations.

Adolescent↗