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Biomedical subjects

B J Cohen

Publications and source records attributed to B J Cohen.

At least 19 recordsLinked to original sources

DecisionNET: database/network support for clinical decision analysts.

DecisionNET is a proposed remote database/wide-area computer network that should cultivate quantitative approaches to medicine by providing rapid access to medical facts, literature citations, decision models, and commentary of specific use to those involved with quantitative clinical decision making. Increasing accessibility to data and providing a forum for exchange of ideas should prove to be a significant asset to clinicians, either as modelers or as clients. Further work will address specific database implementation, development of a query engine, and coordination of the communications infrastructure. DecisionNET provides a unique model for the growth and maintenance of other medical knowledge bases.

Archives

Transient aplastic crisis in patients with sickle cell disease. B19 parvovirus studies during a 7-year period.

OBJECTIVE: To determine (1) the proportion of cases of transient aplastic crisis (TAC) in patients with sickle cell disease due to B19 parvovirus infection in several years, (2) longitudinally, the immune response to B19 parvovirus infection, and (3) whether patients with sickle cell disease experience recurrent or chronic B19 parvovirus infection. DESIGN: Prospective evaluation of patients with sickle cell disease and TAC to find evidence of B19 parvovirus infection and, if present, to document the pattern of serologic response with time. SETTING: Large urban teaching hospital. PATIENTS: Patients younger than 18 years with sickle cell disease who were admitted to the hospital with a diagnosis of TAC or who developed TAC while in the hospital for other reasons. Follow-up serologic studies of B19 parvovirus infection were done in eight patients. MEASUREMENTS/MAIN RESULTS: Serum was tested for B19 parvovirus DNA/viral particles and specific anti-B19 parvovirus IgM and IgG antibodies. B19 parvovirus DNA/viral particles were detected in 11 (21%) of 53 patients with TAC. Specific anti-B19 parvovirus IgM antibodies were detected in 34 (64%) of the 53 patients. Overall, 36 (68%) of 53 patients with TAC had evidence of acute B19 parvovirus infection as shown by the detection of B19 DNA parvovirus and/or specific anti-B19 parvovirus IgM antibodies in acute-phase serum. Follow-up serologic studies in eight patients with acute infection revealed disappearance of B19 parvovirus DNA/viral particles and anti-B19 parvovirus IgM antibodies and persistence of anti-B19 parvovirus IgG antibodies for up to 3 1/2 years after the diagnosis of acute B19 parvovirus infection. No patient had evidence of recurrent or chronic B19 parvovirus infection. CONCLUSIONS: Approximately 70% of cases of TAC in patients with sickle cell disease identified in a 7-year period were caused by acute B19 parvovirus infection. Once detected, anti-B19 parvovirus IgG antibodies remain detectable for several years. There was no evidence of chronic or recurrent B19 parvovirus infection in patients with sickle cell disease.

Adolescent

Haemagglutination by parvovirus B19.

Human parvovirus B19 is a member of the autonomous parvoviridae but in contrast to other members of the genus has not been shown to agglutinate red blood cells. We now report that the virus agglutinates red cells of primate origin, though with plasma-derived virus this activity is masked by the presence of an IgM-like inhibitor. This observation is consistent with the presence on the erythroid precursor target cell of a specific receptor for parvovirus B19.

Animals

cAMP activates the sodium pump in cultured cells of the elasmobranch rectal gland.

The inorganic ion content of rectal gland cells cultured from Squalus acanthias was studied by electron probe analysis in order to determine the effect of stimulation by cAMP. Cell sodium was reduced by 30% (P less than 0.01) at 8 min after exposure to dibutyryl cAMP and theophylline and remained low at 25 and 33 min. Chloride content also fell significantly with stimulation. Although cAMP may activate several transport sites, the results are consistent with a direct effect of stimulation to increase the activity of the sodium pump in shark rectal gland.

Animals

Absence of bacteremia during nasal septoplasty.

Episodes of staphylococcal bacteremia resulting in metastatic infection have occurred in association with nasal septoplasty, and this has suggested the possible need for antimicrobial prophylaxis. In a study designed to measure the actual frequency with which transient staphylococcal bacteremia occurs during nasal septoplasty, 50 healthy patients had blood cultures drawn immediately prior to and during the procedure. Although 46% of the 50 patients studied had their nasal mucosa colonized with Staphylococcus aureus, some of the blood cultures obtained from the 50 patients showed bacterial growth. The authors conclude that staphylococcal bacteremia during nasal septoplasty is a rare occurrence, and that antimicrobial prophylaxis is unnecessary.

Adolescent

Human parvovirus B19 infected fetal liver as a source of antigen for a radioimmunoassay for B19 specific IgM in clinical samples.

A radioimmunoassay for human parvovirus B19 IgM was developed using virus antigen derived from infected fetal liver obtained post mortem. The specificity and sensitivity of this assay, compared with an established radioimmunoassay using serum antigen, was determined by testing 126 sera by both techniques. The results obtained demonstrated close concordance. False negative results were not obtained using fetal liver antigen in 58 tests on known B19 IgM negative sera. Sixty-four IgM positive sera gave positive results using fetal liver derived antigen and the results obtained were quantitatively similar. Four sera gave false positive results using liver antigen but at a very low level. In view of these results we were able to establish a routine diagnostic service for B19 IgM using fetal liver derived antigen, and the results obtained on the first 459 clinical specimens are presented.

Adult

Detection of B19 parvovirus in human fetal tissues by in situ hybridisation.

Evidence of B19 parvovirus infection was sought by in situ hybridisation with biotinylated probes in 65 tissue samples from 32 pregnancies (fetuses, products of conception and/or placentas). Twenty-seven samples were reactive and the results were confirmed by other methods for B19 virus detection in 22 cases. The other methods used were in situ hybridisation with 3H and 35S labelled probes; dot-blot hybridisation with biotin and 32P labelled probes; polymerase chain reaction assay; negative stain and thin section electron microscopy; and radioimmunoassay for B19 antigen. The five false positive results by in situ hybridisation with biotinylated probes were considered to be due to non-specific biotin capture and were more frequent with unfixed samples than with formalin fixed material. It was concluded that while biotinylated probes offered advantages over radioactive probes for detecting B19 DNA by in situ hybridisation, positive findings should be confirmed by other methods.

Biotin

Detection of B19 parvovirus in human fetal tissues by electron microscopy.

We present the electron microscopy observations on samples from 38 pregnancies that were investigated for B19 parvovirus infection. Thirty-four had resulted in fetal loss thought to be due to a virus infection and 22 of the 38 were positive for B19 parvovirus in one or more of the tissues. Twenty-one placentas and 75 fetal tissue samples were examined. Fresh samples were investigated by immune electron microscopy while formalin-fixed tissues were examined as thin sections and by negative staining of tissue extracts with direct electron microscopy. Electron microscopy was more sensitive on fresh than on fixed samples. The ultrastructural observations on thin sections of fixed tissues yielded new information locating B19 parvovirus particles in both nucleus and cytoplasm of infected fetal cells. The diagnostic results of the range of electron microscopy assays were compared with those of two hybridization methods. The fresh samples yielded comparable results from electron microscopy and hybridisation assays but on formalin-fixed materials hybridisation was more sensitive.

Erythema Infectiosum

Hypotension and disseminated intravascular coagulation following intralesional bacillus Calmette-Guérin therapy for locally metastatic melanoma.

Four patients developed serious hypotension and signs of disseminated intravascular coagulation shortly after a second round of Tice bacillus Calmette-Guérin (BCG) injections into locally recurrent cutaneous melanoma satellite nodules. Each of these patients survived following intensive therapy with isoniazid, pyridoxine, steroids, pressors, antibiotics, and cardio-renal support including, in one case, three acute hemodialyses. Plasma specimens from two of the four patients caused gelation of lysate from the amebocytes of Limulus polyphemus, indicating the presence of endotoxin or an endotoxin-like substance. In vitro studies on the BCG preparations led us to conclude that this endotoxin activity in the plasma is not the result of direct injection of endotoxin with the BCG preparation, but rather from release of endotoxin from endogenous sources, such as the intestinal tract during a period of relative hypotension following an allergic reaction. Prior immunity appeared to be the consistent factor in the toxic reactions reported herein. Finally, we present recommendations for serial monitoring of these patients and discuss the use of an alternative agent for intralesional therapy.

Adult

Surgical prophylaxis of malignant melanoma.

A review of a 14-year experience with prophylactic pigmented skin lesion removal is presented. Data obtained during a 4-year interval of this 14-year experience is analyzed specifically. During this 4-year interval, 250 patients with melanoma were seen. Of these patients, 75 with a history of stage I (localized) melanoma and three patients with stage II (history of controlled regionally metastatic melanoma) underwent removal of multiple skin lesions on a prophylactic basis. Of the removed lesions, 28% showed hyperplasia, atypia, dysplasia, or melanoma. Nine unsuspected in situ, or level I melanomas, and three unsuspected invasive melanomas were removed from these 75 melanoma patients while excising lesions prophylactically during the 4-year interval. It is estimated that four to six additional melanomas were prevented by excision of precursor lesions. During the same 4-year interval, an additional 112 of approximately 1000 patients without a previous history of melanoma underwent prophylactic lesion removals. In 31% of the 112 patients, there was a history of melanoma in a first-degree relative. In 22% of the removed lesions there was hyperplasia, atypia, or dysplasia. Three cases of melanoma in situ were detected and it is estimated that an additional three to five cases of melanoma were prevented. Atypical findings occurred in 71, or 63%, of the patients biopsied, which represented 7% of the approximately 1000 patients screened. During the 4-year interval, an average of 17.7 lesions were removed from each of the 190 melanoma and nonmelanoma patients undergoing prophylactic skin lesion excision. This was accomplished in one to four sessions per patient. This average reflects only those patients who underwent one excision or more and does not include those patients treated without operation. When including the nonoperated patients screened during this interval, the average number of lesions removed was 2.7 per patient. Death from new melanomas was prevented during the 14-year period of this study as evidenced by the fact that no patient died or developed metastatic disease from a cutaneous melanoma that was not apparent or known about at the time of first examination.

Dysplastic Nevus Syndrome

In vitro propagation of parvovirus B19 in primary foetal liver culture.

The culture of parvovirus B19 in foetal liver tissue has been described recently. We have established the technique in our laboratory and studied parameters affecting the yield of B19 virus. Replication of the virus was detected by radioimmunoassay for B19 antigen and dot blot hybridization assay of B19 DNA, and the virus was localized by immunofluorescence and thin section electron microscopy. B19 DNA and antigen production became detectable at day 2 and reached a maximum at day 5. Virus particles were seen mainly in cell nuclei, but some cytoplasmic membranes were lined with virus particles. The amount of virus produced depended on the age of the foetus and the cell culture and the concentration of erythropoietin and interleukin 3 in the culture medium.

Cells, Cultured

Evaluation of a synthetic-peptide enzyme-linked immunosorbent assay for immunoglobulin M to human parvovirus B19.

A synthetic peptide corresponding to a part of the virus protein 1-virus protein 2 overlapping region of human parvovirus B19 was used in an indirect enzyme-linked immunosorbent assay. Antibodies of the immunoglobulin (Ig) M class were measured in serum samples from patients with erythema infectiosum and controls. In comparison with an IgM assay using native B19 viral antigen, the peptide antigen assay was 92% sensitive and 87% specific. B19 IgM reactivities were seen in a limited number of children with other viral diseases. Specific IgM reactivities to short synthetic viral peptides have previously been reported only with Epstein-Barr virus. Since other sources of viral antigen are limited, the peptide antigen assay may be a useful alternative for the diagnosis of B19-associated disease in human beings.

Amino Acid Sequence

Congenital parvovirus infection.

A case of congenital parvovirus (B19) viraemia with associated thrombocytopenic purpura and platelet antigen incompatibility in an infant is reported. Results of laboratory investigations indicated that the baby was infected in utero.

Antigens, Human Platelet

Low prevalence of antibody to hepatitis C virus in north east England.

The prevalence of antibodies to hepatitis C virus (anti-HCV) was studied in North East England in blood donors, local multiply transfused patients, local high risk individuals, and chronic liver disease patients. Anti-HCV was detected by enzyme-linked immunosorbent assay (ELISA) in 2/1120 (0.18%) blood donors; 1/84 chronic renal failure patients on haemodialysis who had received 1,992 units of blood (seroconversion rate of 0.05% per unit transfused), 1/207 cardiac patients 6 months post cardiac surgery transfused with 1,403 units of blood (1 anti-HCV pre-operatively, seroconversion rate 0.07%), 40/50 haemophilia A patients treated with commercial factor VIII, and 38/100 intravenous drug users. In addition anti-HCV was detected by ELISA in 5/35 cryptogenic chronic liver disease patients, 5/5 confirmed by recombinant immunoblot assay (RIBA) (14%); 3/30 patients with autoimmune chronic active hepatitis, 2/3 by RIBA (7%); 2/50 primary biliary cirrhosis patients, 1/2 by RIBA (2%); 0/30 alcoholic cirrhosis patients; and 2/9 patients with hepatocellular carcinoma, 1/2 by RIBA (11%). HCV is uncommon in North East England; it may be implicated in the aetiology of a minority of cases of cryptogenic liver disease and less than 5% of autoimmune chronic active hepatitis and primary biliary cirrhosis.

Factor VIII

Blood donor screening for parvovirus B19.

A programme of blood donor screening for parvovirus B19 was conducted from January to May 1990. The main aim of the study was to identify a B19 positive donation that could be used as a source of viral antigen for diagnostic serology. Out of 24,000 donors tested one was positive for B19 antigen by counter current immunoelectrophoresis and over 100 ml of undiluted B19 containing material was obtained. However, much of the positive donation was incorporated in a plasma pool of 28 donations. An acid dissociation technique was used to recover B19 antigen from immune complexes formed in the plasma pool.

Antigens, Viral

Severe anemia due to B19 parvovirus infection in children with acute leukemia in remission.

Two children developed severe anemia with reticulocytopenia while on maintenance chemotherapy for acute lymphoblastic leukemia. Bone marrow examination revealed marked erythroid hypoplasia and giant megaloblasts without evidence of relapse. One patient had evidence of B19 Parvoviremia at the time of severe anemia but failed to produce anti B19 antibodies. Despite the failure to mount an antibody response, the patient had no recurrence of viremia or anemia during the two years of follow-up after the infection. The other patient had no evidence of viremia or elevated anti-B19 antibodies at the time of anemia. However, when his serum was tested 16 months after the episode of anemia, he had elevated IgG and IgM antibodies against B19 parvovirus. The patient did not experience recurrent viremia or anemia over a two year period. Thus, patients with leukemia are at risk to develop severe anemia when infected with B19 parvovirus.

Anemia