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[Monitoring of hemostasis during liver transplantation: contribution of thromboelastography].

Monitoring of coagulation is mandatory during liver transplantation (LT). Standard coagulation tests may be routinely used. However, they give static information and may be inadequate in case of severe coagulation defect. Interest has been recently focused on thromboelastography (TEG) which could give more suitable and rapid information in these cases. Few studies have evaluated the clinical interest of TEG compared to conventional tests. This comparison was the aim of the present study, performed in 89 patients scheduled for LT. The anaesthetic management as well as procedure of transfusion were similar in all patients. Before unclamping, 5000 KIU.kg-1 of aprotinin were injected. Routine tests and TEG were performed at the beginning and end of both pre-anhepatic and anhepatic phases, and 5, 30, 60, and 120 min after the revascularisation of the new liver. A phase of hypocoagulability was observed after unclamping. Biological signs included an increase in activated thromboplastin time, a reduction of alpha angle and maximum amplitude on TEG with a lengthening of its r + k component. A strong correlation existed between maximum amplitude and platelets, maximum amplitude and fibrinogen, alpha and fibrinogen at each time of the surgical procedure. Euglobulin lysis time decreased significantly after clamping, whereas fibrin degradation products increased at the same time. However, typical fibrinolysis with a clot lysis index (CLI) below 55% was only observed in 15 patients. Twelve of them had a CLI value reaching 0%, associated with severe generalized oozing. Aprotinin (200,000 to 600,000 KIU) corrected these abnormalities. These results show that TEG may not be very helpful to determine whether platelets or fibrinogen are involved in the phase of hypocoagulability detected after unclamping.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Human parvovirus B19 infection in organ transplant recipients.

We report a 61-yr-old kidney transplant recipient with human Parvovirus B19 (HPV B19) infection presenting as a severe pancytopenia 1 month after transplantation. Bone marrow aspiration revealed severe erythroid hypoplasia with giant and dystrophic proerythroblasts. Bone marrow cells were positive for HPV B19 DNA detected by polymerase chain reaction (PCR). Pancytopenia resolved shortly after administration of intravenous immunoglobulins. Nineteen cases of HPV B19 infection in organ transplant recipients have been so far reported in the literature. Immunocompromised patients should be considered at risk from developing symptomatic HPV B19 infections. In such patients, specific anti-HPV B19 IgM and IgG antibodies may be absent or transient and therefore their negativity cannot rule out the diagnosis of HPV B19 infestation. Bone marrow smear morphological findings may suggest the diagnosis but testing for viral DNA by PCR is mandatory. Patients may spontaneously recover. However, since specific anti-viral therapy is not currently available, intravenous immunoglobulin administration appears to be the more efficacious treatment.

DNA, Viral↗

Intensive chemotherapeutic regimens against acute leukemia transiently suppress asthma symptoms but do not lead to long-term relief.

In some very rare cases children suffer from a combination of asthma and a malignant disease. This study investigated whether intensive chemotherapy might have a positive effect on asthma in these special cases and whether asthma generally relapses after completion of chemotherapy. The authors monitored clinical outcome and lung function of 43 children with acute lymphoblastic leukemia and non-Hodgkin lymphoma who received chemotherapy at the University Children's Hospital of Greifswald between 1993 and 1998. Cytostatic chemotherapy was administered according to the German treatment protocols. Two of the 43 patients had asthma before leukemia was diagnosed. During the course of chemotherapy, asthma symptoms diminished promptly after beginning of chemotherapy but asthma was rediagnosed after completion of chemotherapy in both cases. The third patient developed asthmatic symptoms shortly after completion of chemotherapy for the first time. It can be stated that chemotherapy does not essentially cure asthma. Therefore, it seems mandatory to perform follow-up lung testings after chemotherapy, especially in patients with asthma.

Antineoplastic Agents↗

Neurosyphilis presenting with optic neuropathy. Report of a case and review.

A patient with neurosyphilis, presenting with severe ocular impairment due to optic neuropathy, is described. In such a case, a low index of clinical suspicion and improper use of syphilitic serologic tests may delay diagnosis. However, specific tests of serum and cerebrospinal fluid are mandatory for the diagnosis. Treatment evaluation necessitates the follow-up of serology and cerebrospinal fluid cell count. Recent changes of therapy recommendations in subjects with neurosyphilis and in those syphilitic patients co-infected with HIV are mentioned.

Aged↗

Diagnosis of acute type B hepatitis by a solid phase u-antibody capture radioimmunoassay for IgM class antibody to hepatitis B core antigen: a diagnostic proposal based on a prospective study.

The diagnostic and prognostic significance of IgM anti-HBc, studied by a solid phase u-antibody capture radioimmunoassay at a serum dilution of 1:4000, was prospectively evaluated in 73 adult patients with acute hepatitis seropositive for hepatitis B surface antigen (HBsAg). Of the 73 cases, 20 (27.4%) cleared their HBsAg within 6 months, while the remaining 53 (72.6%) did not. HBsAg seroconversion to its antibody occurred in 15 (93.8%) of the 16 patients positive for IgM anti-HBc with S/N ratios above 5.0, as did 5 (26.3%) of the 19 with S/N ratios between 2.1 to 5.0, and none (0%) of the 38 negative for IgM anti-HBc (S/N ratios less than 2.1). Therefore, a S/N ratio of IgM anti-HBc above 5.0 is diagnostic for acute type B hepatitis. However, low S/N ratios (2.1-5.0) of IgM anti-HBc were observed in the early stage of some patients with acute type B hepatitis, and would increase to a level greater than 5.0 when assayed again 1-2 weeks later. It was therefore suggested that repeated testing of anti-HBc IgM is mandatory for accurate diagnosis of acute type B hepatitis in patients whose initial serum specimens showed low S/N ratios of IgM anti-HBc. According to this criterion, only 22 (30.1%) of the 73 patients with acute hepatitis seropositive for HBsAg in Taiwan were true acute type B hepatitis, of whom 2 (9.1%) subsequently became chronic HBsAg carriers, while the remaining 51 (69.9%) were chronic HBsAg carriers with other superimposed forms of acute hepatic injury.

Adult↗

Serological confirmation of Chagas' disease by a recombinant and peptide antigen line immunoassay: INNO-LIA chagas.

Although screening for Trypanosoma cruzi antibodies is mandatory in most South American countries, current tests are insensitive and have poor specificity. A recently optimized line immunoassay (the INNO-LIA Chagas assay) for the serological confirmation of Chagas' disease was evaluated at a large blood bank in São Paulo, Brazil. Sera from blood donors who reacted in at least one of three serological screening assays (n = 1,604) and who returned for a follow-up were retested, and the donors were interviewed to assess their epidemiological risk. The results obtained by the confirmatory assay evaluated in this study were compared to those obtained by the three different screening assays. Upon consideration of the consensus results obtained by the three different screening assays as a "gold standard," the INNO-LIA Chagas assay showed a sensitivity of 99.4% (95% confidence interval [CI], 98.3 to 99.9) and a specificity of 98.1% (95% CI, 96.6 to 99.0) for positive (n = 503) and negative (n = 577) sera. The INNO-LIA Chagas assay confirmed the results for significantly larger numbers of positive samples of at-risk individuals independent of the number of positive screening tests (P = 0.017, Mantel-Haenszel test). In conclusion, the INNO-LIA Chagas assay reliably confirmed the presence of antibodies to T. cruzi and can be implemented as a confirmatory assay for Chagas' disease serology.

Animals↗

Blockade of the integrin alphaLbeta2 but not of integrins alpha4 and/or beta7 significantly prolongs intestinal allograft survival in mice.

BACKGROUND: Small bowel transplantation remains a difficult therapeutic option endangered by a high rate of rejection and infectious complications. To improve these clinical results, it is mandatory to set up animal models to test alternative immunosuppressive regimens which may lead to immunotolerance. AIMS: To determine the value of blockade of alphaLbeta2 (LFA-1) and alpha4 and beta7 integrins (alpha4beta1, alpha4beta7, and alphaEbeta7) in the prevention of rejection of fetal small bowel grafts in mice and the effect of the association of calcineurin dependent drugs in anti-LFA-1 treated mice. METHODS: Adult recipient mice engrafted with allogeneic fetal small bowel received a short course of anti-alpha4 and/or anti-LFA-1 monoclonal antibodies (mAb) with or without FK506 or cyclosporin A. In addition, in a set of experiment, beta7-/- mice were used as recipients. Graft biopsies were performed and processed for standard histology. RESULTS: Blockade of the pathways of the integrins alpha4 and beta7 had a modest or no effect on intestinal graft survival. In contrast, transitory, short administration of anti-LFA-1 monoclonal antibody alone, when started before engraftment (day -1), allowed long term survival of intestinal grafts, even when associated with calcineurin dependent drugs. However, early withdrawal of FK506 reversed the immunosuppressive effect of anti-LFA-1 treatment. CONCLUSION: These results suggest that firstly, anti-LFA-1, but not anti-alpha4 mAb treatment, may be useful in improving the results of intestinal transplantation, and secondly, that this treatment is not incompatible with long term administration of tacrolimus currently used in the prevention of small bowel graft rejection in humans.

Animals↗

Excimer laser-assisted recanalization of long, chronic superficial femoral artery occlusions.

PURPOSE: To examine the safety and efficacy of excimer laser-assisted angioplasty (ELA) for recanalization of superficial femoral artery (SFA) occlusions. METHODS: Data were analyzed from 318 consecutive patients (207 men; mean age 64.2 +/- 10.7 years, range 33-91) who underwent ELA of 411 SFAs with chronic occlusions averaging 19.4 +/- 6.0 cm in length. More than 75% of patients had severe claudication (category 3). Critical lower limb ischemia with rest pain or minor tissue loss was present in 6 and 15 patients, respectively. The mean ankle brachial index (ABI) before and after exercise was 0.62 +/- 0.15 and 0.40 +/- 0.18, respectively. RESULTS: The initial attempt (crossover approach 89.7%, antegrade 6.6%, transpopliteal 3.6%) to cross the occlusion with an excimer laser catheter was successful in 342 (83.2%) of 411 limbs. A secondary attempt performed in 44 of 69 failed cases was successful in 30 limbs, increasing the technical success rate to 90.5% (372/411). Complications included acute reocclusion (4, 1.0%), perforation (9, 2.2%), and distal thrombosis/embolization (16, 3.9%). Postprocedurally, 219 (68.8%) patients were asymptomatic; mild (category 1) or moderate (category 2) claudication remained in 53 (16.6%) and 26 (8.2%) patients, respectively. The primary patency at 1 year was 33.6%. In the majority of patients, reocclusion was treatable on an outpatient basis. The 1-year assisted primary and secondary patency rates were 65.1% and 75.9%, respectively. CONCLUSIONS: Long SFA occlusions can be recanalized safely and successfully by ELA. However, to maintain patency and quality of life, intensive surveillance using objective testing followed by prompt repeat intervention are mandatory.

Adult↗

Exercise-related syncope in the young athlete: reassurance, restriction or referral?

A common event in young adults, syncope is usually benign and only rarely requires more than simple reassurance. However, exercise-related syncope always requires investigation because it may be the only symptom that precedes a sudden cardiac death. Syncope that occurs during exercise tends to be more ominous than that occurring in the postexertional state. During the physical examination, the cardiovascular system should be evaluated carefully. An electrocardiogram is mandatory and requires close scrutiny, with further testing ordered as indicated. The investigation of syncope should specifically exclude known pathologic diagnoses before a complete return to activity is permitted. In cases where a diagnosis is not clearly established, consultation or referral may be warranted.

Adult↗

Algorithm for recall of HIV reactive Indian blood donors by sequential immunoassays enables selective donor referral for counseling.

BACKGROUND: HIV/AIDS pandemic brought into focus the importance of safe blood donor pool. AIMS: To analyze true seroprevalence of HIV infection in our blood donors and devise an algorithm for donor recall avoiding unnecessary referrals to voluntary counseling and testing centre (VCTC). MATERIALS AND METHODS: 39,784 blood units were screened for anti-HIV 1/2 using ELISA immunoassay (IA-1). Samples which were repeat reactive on IA-1 were further tested using two different immunoassays (IA-2 and IA-3) and Western blot (WB). Based on results of these sequential IAs and WB, an algorithm for recall of true HIV seroreactive blood donors is suggested for countries like India where nucleic acid testing or p24 antigen assays are not mandatory and given the limited resources may not be feasible. RESULTS: The anti-HIV seroreactivity by repeat IA-1, IA-2, IA-3 and WB were 0.16%, 0.11%, 0.098% and 0.07% respectively. Of the 44 IA-1 reactive samples, 95.2% (20/21) of the seroreactive samples by both IA-2 and IA-3 were also WB positive and 100% (6/6) of the non-reactive samples by these IAs were WB negative. IA signal/cutoff ratio was significantly low in biological false reactive donors. WB indeterminate results were largely due to non-specific reactivity to gag protein (p55). CONCLUSIONS: HIV seroreactivity by sequential immunoassays (IA-1, IA-2 and IA-3; comparable to WHO Strategy-III) prior to donor recall results in decreased referral to VCTC as compared to single IA (WHO Strategy-I) being followed currently in India. Moreover, this strategy will repose donor confidence in our blood transfusion services and strengthen voluntary blood donation program.

Adult↗

Treatment of chronic anti-HBe-positive hepatitis B with interferon-alpha.

We studied the prevalence of long-term responders to interferon-alpha (IFN-alpha) treatment (undetectable levels of serum IgM anti-HBc, HBV-DNA and normal ALT values for 3 years) in 53 anti-HBe-positive chronic hepatitis B patients. Forty-two of them were treated with (6-18 MU) alpha-2a-recombinant-IFN t.w. for 4-6 months, and the remaining 11 with 10 MU of lymphoblastoid-IFN thrice weekly for 6 months. At the end of treatment, HBV-DNA levels were undetectable and ALT values within the normal range in 34 of 53 patients (60%); IgM anti-HBc levels decreased in all the 34 patients, falling below 10 PEI U in 2/34 (6%). Response to treatment was maintained throughout the follow-up (mean 3 years, range 2-7 years) in five patients (9.4%). The remaining 29 patients experienced HBV reactivation within median follow-up of 6 months (range 1-22 months; 90% of cases within 12 months). Overall 4/9 long-term responders (44.4%) cleared serum HBsAg. In conclusion, chronic anti-HBe-positive hepatitis B has a lower IFN treatment response rate than the HBeAg-positive form; however, among long-term responders, the incidence of serum HBsAg clearance is comparable in the two forms. Because of the high rate of relapses, stringent monitoring criteria (HBV-DNA, IgM anti-HBc and ALT monthly tested for at least 12 months) are mandatory.

Adolescent↗

[Prevention and treatment of hepatitis B in patients on hemodialysis and vaccination of hemodialysis health personnel against hepatitis B].

The prevalence and incidence of hepatitis B in hemodialysis patients in Croatia have been estimated to 1.3% and 0.03%, respectively. HBV infection in dialysis patients is usually asymptomatic, has a prolonged course, and progresses to chronic HBsAg hepatitis in 50% of cases. Some 15%-40% of HBsAg carriers on dialysis will develop cirrhosis, liver decompensation or hepatocellular carcinoma. Strict adherence to the standard infection prevention measures, continuous monitoring of HBV markers in patients on hemodialysis, patient and personnel immunization and hepatitis B treatment in hemodialyzed patients are mandatory. Each new patient in a dialysis center must be tested for HBV markers irrespective of prior immunization. All patients in the center should be routinely screened every 3-4 months. HBV immunization is mandatory for all patients on dialysis. In patients with uremia the anti-HBs antibody production is decreased (antibodies will develop in 50%-60% of cases after immunization). It is recommended to immunize all patients with progressive kidney disease, preferably in the preterminal stage. Hepatitis B therapy is recommended in all patients with biopsy proven chronic liver disease. Patients should be treated with standard interferon alpha and/or lamivudine, or peginterferon alpha monotherapy. Hepatitis B treatment is most important in kidney and/or liver transplant candidates. HBV immunization is obligatory for all hospital personnel who are in close contact with infected patients and infective materials.

Hepatitis B↗

Effect of the contents and form of rabies glycoprotein on the potency of rabies vaccination in cattle.

One of the methods used for controlling cattle rabies in Brazil consists of vaccination. Sometimes, however, rabies occurs in cattle supposedly protected. Since rabies vaccine batches are officially controlled by tests performed on laboratory animals, it is questionable whether the minimal mandatory requirements really correspond to immunogenicity in the target species. We have analyzed the association among potencies of rabies vaccines tested by the NIH test, the contents and form (free-soluble or virus-attached) of rabies glycoprotein (G) in the vaccine batches, and the virus-neutralizing antibodies (VNA) titers elicited in cattle. No correlation was found between G contents in the vaccine batches and the NIH values, whatever the presentation of G. There was no correlation either between NIH values and VNA titers elicited in cattle. There was, however, a positive correlation (r = 0.8681; p = 0.0001) between the amounts of virion-attached G present in the vaccine batches and VNA elicited in cattle. This was not observed when the same analysis was performed with total-glycoprotein or free-soluble glycoprotein. The study demonstrated that NIH values can not predict the effect of the immunogen in cattle. On the other hand, the quantification of virus-attached rabies glycoprotein has a strong correlation with VNA elicited in cattle.

Animals↗

Preoperative testing for cataract surgery.

A survey was carried out to examine variation in preoperative testing of healthy patients scheduled to undergo cataract surgery in Canada. The results showed significant variations in which investigations are mandatory and in how close to the time of surgery the tests had to be done. A literature review questioning the value of routine preoperative testing is presented. Eliminating low-yield pre-operative screening tests is a safe way to reduce expenditures on cataract surgery without compromising patient care.

Canada↗

Flow cytometric immunphenotyping of epithelial cancer cells in effusions--technical considerations and pitfalls.

BACKGROUND: Data regarding the role of flow cytometry (FCM) in the characterization of malignant effusions are limited to date. In the present study, we optimized the conditions for FCM immunphenotyping of effusions using a four-color analysis and investigated aspects related to the advantages and limitations of this method in this setting. METHODS: FCM analysis optimization for the study of epithelial cells was undertaken using five carcinoma cell lines, and subsequently applied to malignant pleural and peritoneal effusions using antibodies against epithelial and mesothelial markers (Ber-EP4 and EMA), CD138, and integrin subunits. FCM of frozen versus fresh specimens and the performance of FCM compared to immunhistochemistry were evaluated. RESULTS: FCM optimization was achieved and applied to clinical specimens, with resulting detection of epithelial markers and adhesion molecules on cancer cells. Frozen clinical specimens and cell lines showed reduced CD138 expression compared to fresh specimens, with conservation of the remaining epitopes. FCM generally showed comparable performance to immunhistochemistry. CONCLUSIONS: FCM is an effective method for characterization of cancer cells in clinical effusion specimens in both the diagnostic and research setting, and is comparable to immunhistochemistry in terms of sensitivity and specificity, with the additional advantage of providing quantitative data. The majority of epitopes are conserved in frozen cells, but a minority may be lost, suggesting that the thorough testing of each antibody in both conditions is mandatory.

Antibodies↗

Patient information leaflets for medicines: using consumer testing to determine the most effective design.

Comprehensive medicine information leaflets for patients are now mandatory across the European Union. In 1997, the European Commission (EC) proposed a prescriptive 'model' for the leaflets and a method for consumer testing. This exploratory study compared consumers' ability to use a leaflet based on the EC model leaflet and an alternative leaflet based on best practice in information design (Mark II). The leaflets were tested in two matched groups of 20 consumers, who were required to find, and understand, 15 pieces of information in the leaflets. The target that each question should be answered correctly by 16 out of 20 consumers, was achieved for three of the 15 points in the EC leaflet, compared with eight in the Mark II leaflet. Open questioning confirmed the problems with the EC leaflet, including a failure to understand key concepts about medicine interactions and contraindications. This research demonstrates the benefits of consumer testing, ensuring that leaflets are patient-orientated. A rigid model leaflet would prevent these benefits from being utilised.

Aged↗

Prevalence and mechanisms of erythromycin resistance in group A and group B Streptococcus: implications for reporting susceptibility results.

Increased rates of erythromycin resistance among group B Streptococcus (GBS) and group A Streptococcus (GAS) have been reported. Cross-resistance to clindamycin may be present, depending on the mechanism of resistance. We determined the prevalence of macrolide-resistant determinants in GBS and GAS isolates to guide the laboratory reporting of erythromycin and clindamycin susceptibility. Susceptibilities were determined by the disk diffusion and broth microdilution methods. Inducible and constitutive resistance to clindamycin was determined by the double-disk diffusion method. The presence of the ermTR, ermB, and mefA genes was confirmed by PCR. Of the 338 GBS isolates, 55 (17%) were resistant to erythromycin, whereas 26 (8%) were resistant to clindamycin. The erm methylase gene was identified in 48 isolates, 22 of which had inducible resistance to clindamycin and 26 of which had constitutive resistance to clindamycin. The remaining seven resistant isolates had mefA. Of the 593 GAS isolates, 49 (8%) and 6 (1%) isolates were resistant to erythromycin and clindamycin, respectively. Erythromycin resistance was due to mefA in 33 isolates, whereas 14 isolates had erm-mediated resistance (9 isolates had inducible resistance and 5 isolates had constitutive resistance). In our population, erythromycin resistance in GAS was predominantly mediated by mefA and erythromycin resistance in GBS was predominantly mediated by erm. Regional differences in mechanisms of resistance need to be taken into consideration when deciding whether to report clindamycin susceptibility results on the basis of in vitro test results. Testing by the double-disk diffusion method would be an approach that could be used to address this issue, especially for GAS.

Adolescent↗

Tuberculosis surveillance: lessons from a cluster of skin test conversions.

Mycobacterium tuberculosis has reemerged as a significant public health problem. Elderly persons, especially those in long-term care facilities, are among those at high risk for infection with M. tuberculosis. Frequently, their symptoms are not clearly indicative of M. tuberculosis, and the diagnosis may thus be missed. We discuss the investigation of a cluster of skin test conversions on one locked unit in our long-term care facility. During the epidemiologic investigation, four of 25 patients who had previously had negative results of purified protein derivative testing (16%) and eight of 95 employees (11%) had skin test conversions. Despite a comprehensive, costly evaluation, the index case was not found. We identified weaknesses in our employee and patient M. tuberculosis surveillance programs. Employee baseline purified protein derivative testing data were inadequate. Annual skin tests for employees with previously negative results were not mandatory. There was no mechanism in place to encourage compliance. We developed a plan to educate personnel about the reemergence of M. tuberculosis, signs and symptoms in elderly patients, and the placement and interpretation of purified protein derivative skin tests. Documentation of purified protein derivative surveillance of both patients and employees was computerized. The number of inpatient and outpatient negative-pressure rooms was increased. Appropriate personal protective equipment was made available for use in high-risk situations.

Aged↗