Human papilloma virus vaccination in patients with an aggressive course of recurrent respiratory papillomatosis

In the case of an aggressive course of recurrent respiratory papillomatosis (RRP), adjuvant therapy can be used besides surgery. The aim of the study was to investigate the influence of vaccination with a quadrivalent vaccine against human papilloma viruses (HPV) types 6, 11, 16 and 18 on the course of RRP. Eleven subjects aged 13–46 years with a rapid growth of laryngeal papillomas were included in the study. They were vaccinated with three doses of the quadrivalent prophylactic HPV vaccine (Silgard^®, MSD) and followed up for 12–52 months. The intervals between the successive surgical procedures, the extension of the disease (Derkay score) at each surgery, and the number of surgical procedures per year before vaccination and after its completion were compared. The mean interval between the surgical procedures was 271.2 days before the vaccination and 537.4 days after it (p = 0.034). The mean number of surgeries per year was 2.16 before the vaccination and 0.93 after it (p = 0.022). The Derkay score did not change significantly after vaccination. Complete remission of the disease was observed in one patient, partial response to the vaccination was observed in seven patients and no response was observed in three patients. In conclusion, vaccination with the quadrivalent HPV vaccine can favorably influence the course of RRP in patients with the rapid growth of the papillomas. It significantly prolongs the intervals between the surgical procedures and reduces the number of procedures needed in the majority of patients. The present investigation can serve as a pilot study for further research. For a final conclusion a longer follow-up and studies on more patients are necessary.     

Gene expression profiling reveals alteration of caspase 6 and 14 transcripts in normal skin of keloid-prone patients

Excessive scar formation in keloids points to altered tissue modeling and repair mechanisms. Dysregulation of cytokine and apoptotic cascades and their downstream signaling pathways might have a role in keloid development. Total RNA was isolated from biopsied keloidal tissue and adjacent normal skin of black patients, white patient’s scars, and normal skin of black and white patients, with normal wound healing. Apoptosis, cytokine and NFkB pathway microarrays were used to study and compare gene expression levels. Real-time PCR was used to verify microarray results in original samples and a separate, validation-set of samples. Significant differences were observed in the expression levels of members of caspase, cytokines and MAP kinase pathways, between the normal skin of keloid-prone and normal skin of keloid-resistant patients. Specifically, expression of caspase 6, and caspase 14 genes were different between normal skin of keloid-prone individuals and normal skin of keloid-resistant patients. Our results suggest that normal skin of keloid-prone individuals constitutively expresses a distinct gene profile which might contribute to their susceptibility to develop keloids.     

Unusual radiographic presentation of an aneurysmal bone cyst of the mandible

An 11-year-old girl was referred because of a painless firm swelling in the right posterior mandible that had started 2 months previously. A panoramic radiograph showed a nonspecific finding of a tiny discreet shadow following the lower border of the mandible, without any radiographic signs of radiolucency in the affected area or discontinuity of the lower border. However, multislice computed tomography (MSCT) findings were suggestive of an aneurysmal bone cyst, and histopathological findings revealed a diagnosis of aneurysmal bone cyst. Complete surgical excision followed by extensive cortical bone curettage was done, and no recurrence has been observed in the past 5 years. A differential diagnosis list is included, and extended with fibrous dysplasia according to the radiographic findings. To the best of our knowledge, this is the first case of a jaw aneurysmal bone cyst with unusual initial radiographic findings. Furthermore, a ground-glass appearance on MSCT scans suggested fibrous dysplasia. The present case highlights the need for accurate differential diagnosis of the lesion described to obtain the correct diagnosis in a timely manner and plan the appropriate treatment.     

Human papillomavirus infection in relation to mild dyskaryosis in conventional cervical cytology

PURPOSE OF INVESTIGATION: To establish the prevalence and distribution of high-risk human papillomavirus (HPV) genotypes in Slovene women with repeat mild dyskaryosis, and to evaluate three molecular methods for the detection of HPV that could be used as a complementary method to cervical cytology. METHODS: In this prospective study 148 women with three subsequent cervical cytologic tests within two years showing mild dyskaryosis were enrolled. HPV infection was determined using three molecular tests: Hybrid Capture II and two variants of polymerase chain reaction (PCR-PGMY11/PGMY09 and PCR-CPI/CPIIG). RESULTS: HPV was detected in 17 of the 45 women aged < or =30 years and in 21 of the 103 women aged >30 years (37.8% vs 20.4%, p = 0.04). The most common genotype was HPV 16 detected in eight (21.1%) women, the next were HPV 53 and HPV 51, each detected in five (13.2 %) women. The three molecular methods matched in 92.9%. CONCLUSION: Low prevalence of HPV infections indicates that cervical screening programmes in Slovenia are overburdened with mild dyskaryosis. Repeat cytology is not reliable; HPV testing might be useful as a complementary method.     

Formation of blocking lesions at identical DNA sequences by the nitrosourea and platinum classes of anticancer drugs

cis-Diamminedichloroplatinum (II) (cisplatin) compounds and the chloroethylnitrosoureas are two different classes of anticancer drugs that work by modifying DNA covalently. We have compared the platinating drug cisplatin with the alkylating drug bischloroethylnitrosourea and other chloroethylnitrosoureas by modifying double stranded DNA in vitro and identifying blocking lesions that impede the progress of Escherichia coli DNA polymerase. Despite their very different structures and reactivities, cisplatin and the chloroethylnitrosoureas from primary blocking lesions at identical sequences, those containing adjacent guanosines on the same DNA strand. In tumor virus SV 40 DNA, a very strong target for both types of drugs is the regulatory sequence GGGCGG, which is repeated six times and is an important sequence for viral replication and an essential sequence for expression of the viral transforming gene. Sequences related to these GC box elements are known to be present in the flanking regions of many retroviruses and oncogenes, thus raising the possibility that the targeting of these sequences in tumor cells contributes to drug activity.     

Megakaryocyte progenitors in paroxysmal nocturnal haemoglobinuria are sensitive to complement

Abstract: We have investigated growth in vitro of bone marrow megakaryocytic progenitors (CFU-Mk) in 7 patients with paroxysmal nocturnal haemoglobinuria (PNH) to determine the sensitivity of CFU-Mk to complement. Bone marrow light density mononuclear cells were exposed to fresh or heat-inactivated AB human serum in the presence of medium or isotonic sucrose solution. We found that the proliferative activity of bone marrow CFU-Mk in PNH patients was significantly lower than in controls. In addition, the number of CFU-Mk in PNH bone marrow cells exposed to isotonic sucrose and complement was reduced to 25% of that in PNH cells exposed to isotonic sucrose without complement. In conclusion, our finding showed an increased sensitivity of CFU-Mk in PNH bone marrow cells to complement, supporting the hypothesis that the PNH defect is present at the level of CFU-Mk.     

Evaluation of the amplicor HCV test: Experiences after 1 year of routine use in a diagnostic laboratory

Summary To evaluate the usefulness of a standardized commercial amplification assay for detection of hepatitis C virus (HCV) RNA, Amplicor® HCV Test (Roche), a total of 1,204 serum samples from 888 patients was examined. Seven out of 443 anti-HCV-negative samples, 638 out of 729 anti-HCV-positive samples and four out of 32 anti-HCV-indeterminate samples tested HCV RNA positive by Amplicor® in initial testing. One false-negative and five false-positive Amplicor® results were found in initial testing, giving an overall sensitivity and specificity of the Amplicor® HCV Test of 99.8% and 99.1%, respectively. Our study confirmed that the Amplicor® HCV Test is a practical, rapid, sensitive and specific assay for detection of HCV RNA. However, the results must be interpreted with some caution and with the patient's anti-HCV status and clinical data in mind.

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Evaluierung des HCV-Amplicor®-Tests: Erfahrungen aus einjähriger Anwendung im Routinelabor

Zusammenfassung Ein standardisierter kommerzieller Amplifikationsassay zum Nachweis von Hepatitis C Virus (HCV)-RNA, der Amplicor® HCV Test (Roche) wurde an 1.204 Serumproben von 888 Patienten auf seine Brauchbarkeit geprüft. Sieben von 443 anti-HCV-negativen Proben und 638 von 729 anti-HCV positiven Proben sowie vier von 32 anti-HCV unbestimmten Proben ware mit Amplicor® positiv bei erster Testung. Die Ergebnisse der ersten Testung erwiesen sich in einem Fall als falsch negativ und in fünf Fällen als falsch positiv. Für den Amplicor® HCV-Test ergibt sich daraus eine Sensitivität von 99,8% und eine Spezifität von 99,1%. Unsere Studie bestätigte, daß der Amplicor® HCV-Test ein praktischer, rasch durchführbarer, sensitiver und spezifischer Test für den Nachweis von HCV RNA ist. Die Ergebnisse müssen jedoch mit Vorsicht bewertet werden, wobei immer der anti-HCV Status des Patienten und seine klinischen Daten herangezogen werden sollten.

     

Health effects in a casual sample of immigrants to Israel from areas contaminated by the Chernobyl explosion.

We analyzed questionnaire and physician examination data for 1560 new immigrants from the former USSR divided into three groups by potential exposure to Chernobyl radiation. Two groups were chosen according to soil contamination by cesium-137 at former residences, as confirmed by our findings in a 137Cs body burden study. The third group consisted of "liquidators," persons who worked at the Chernobyl site after the disaster. Liquidators had greater self-reported incidences of symptoms commonly accepted as acute effects of radiation exposure, increases in prevalence of hypertension, and more health complaints. Excesses of bronchial asthma and health complaints were reported in children from the more exposed communities. Asthma prevalence in children potentially exposed in utero appears to be increased eightfold. Older adults from more exposed areas had more hypertension as assessed by history and measurements. These findings suggest the possible association of radiation exposure with several nonmalignant effects.     

Low prevalence of hepatitis C virus infection among human immunodeficiency virus type 1-infected individuals from Slovenia and Croatia

The prevalence of hepatitis C virus (HCV) infection in the population of human immunodeficiency virus 1 (HIV-1)-infected individuals from Slovenia and Croatia was determined. One hundred and sixty-six out of a total of 188 Slovenian HIV-1-infected individuals and 120 subjects who were randomly chosen out of a total 342 Croatian HIV-1 antibodies-positive individuals were tested for HCV infection. Detection of HCV antibodies was carried out by a third generation enzyme-linked immunoassay (ELISA) and the positive samples were additionally tested by a third generation immuno-blot assay. Additionally, the presence of HCV RNA was determined in all serum samples by a qualitative polymerase chain reaction (PCR). Twenty-four (14.5%) out of 166 Slovenian and 18 (15.0%) out of 120 Croatian HIV-1-infected individuals were HCV antibodies-positive. Nineteen out of 24 (79.2%) Slovenian and 13 out of 18 (72.2%) Croatian anti-HCV positive individuals were also viremic. HCV RNA was not detected in any of 244 HCV antibodies-negative/HIV-1-infected individual from both countries. A significant difference in the prevalence of HCV infection between blood (77.8% in Slovenia and 66.7% in Croatia) and sexual exposure risk groups (1.6% in Slovenia and 6.6% in Croatia) was found in both countries. In a study carried out on the highest proportion of entire population of HIV-1-infected individuals from a certain country or geographic region, Slovenia and Croatia were identified as countries with the second and third lowest prevalence of HCV infection among HIV-1/HIV-2 infected individuals worldwide.     

The role of core antigen detection in management of hepatitis C: a critical review.

Several assays in research format and two commercial assays for the detection of hepatitis C virus (HCV) core protein or HCV core antigen have been developed in recent years. In order to elucidate the role and significance of HCV core antigen detection in the diagnosis and management of hepatitis C, we reviewed 56 studies published in peer-reviewed journals until September 2004. Evaluations in transfusion settings showed that the HCV core antigen assay detects HCV infection, similarly as nucleic acid techniques (NAT), between 40 and 50 days earlier than the current third generation HCV antibody screening assays. HCV core antigen levels closely track HCV RNA dynamics, and allow clinical monitoring of a patient's therapy, independently of HCV genotype, however, mainly in the samples with HCV RNA levels above 20,000 IU/ml. Considering the lower sensitivity of HCV core antigen detection in comparison to NAT, the HCV core antigen assay is not practical for the determination of the end of treatment response and sustained viral response, but could be useful for the determination of early viral response in the pegylated interferon-alpha and ribavirin treated patients infected with HCV genotype 1. The HCV core antigen detection is a viable tool for study of hepatitis C pathogenesis. The HCV core antigen can be used as a marker of HCV replication in anti-HCV positive individuals in the areas of the world that cannot afford NAT and/or in the settings that are not equipped or competent to perform HCV RNA testing. Because the manufacturer of HCV core antigen assays recently stopped an active marketing of these assays in several countries, it will, unfortunately and probably, never be possible to determine the actual potential and usefulness of HCV core antigen testing in the management of hepatitis C.