The value of fine-needle aspiration biopsy in patients with nodular thyroid disease divided into groups of suspicion of malignant neoplasms on clinical grounds.

The accuracy of clinical diagnosis and fine-needle aspiration biopsy (FNAB) was evaluated in 169 patients surgically treated for nodular thyroid disease. Patients were divided into three groups with high, moderate, or low suspicion of malignant neoplasms on clinical grounds without previous knowledge of cytologic or histologic results. Histologic examination revealed an overall malignant neoplasm rate of 23%; the rate was 71%, 14%, and 11% for the groups with high, moderate, and low suspicion, respectively. The FNAB diagnostic interpretations of malignant and uncertain were considered positive. Overall sensitivity, specificity, and accuracy for FNAB were 92%, 71%, and 75%, respectively. Sensitivity in the high-, moderate-, and low-suspicion groups was 95%, 89%, and 88%, respectively; specificity was 88%, 72%, and 67%, respectively; and accuracy was 93%, 75%, and 69%, respectively. In our opinion, all patients in the group with high clinical suspicion need surgical treatment whatever the FNAB result; those with lower degrees of clinical suspicion and malignant or uncertain FNAB result [corrected] should also undergo surgery.

Immunity to diphtheria, pertussis, tetanus, and poliomyelitis in children with acute lymphocytic leukemia after cessation of chemotherapy.

Antibody titers to diphtheria, pertussis, tetanus, and poliomyelitis (types I to III) were measured in previously vaccinated children with acute lymphocytic leukemia in remission after cessation of therapy. The response to revaccination one year after therapy was stopped was also studied. The patients' antibody titers were compared with those of healthy children, matched for age and sex. Two groups of patients were studied: one group (group A, N = 30) was given two drugs (6-mercaptopurine, methotrexate); the other group (group B, N = 19) was given three drugs (6-mercaptopurine, methotrexate, and cyclophosphamide) for maintenance treatment. In general, the patients' antibody titers were lower than those of healthy children, but in most patients they were still at levels considered to be protective. No significant differences in antibody levels between the two patient groups were found. A spontaneous rise in antibody titers in the first year after termination of therapy was not observed. After revaccination the rise in antibody titers was correlated with preexisting antibody titers in the same way in patients as in healthy children, and the antibody titers in patients and in healthy control subjects were on roughly the same level.

Tumor markers for ovarian cancer. A comparative immunohistochemical and immunocytochemical study of two commercial monoclonal antibodies (OV632 and OC125).

A comparative immunohistologic and immunocytologic study was performed to assess the immunoreactivity of the monoclonal antibodies OC125 and OV632, both directed at antigens present on epithelial ovarian tumors. OC125 reacted with 53 of 59 ovarian carcinomas, 20 of 20 uterine carcinomas, and 25 of 111 nongynecologic tumors (including 20 of 38 breast carcinomas). OV632 was demonstrated in 47 of 59 ovarian carcinomas, 11 of 20 uterine carcinomas, and only 7 of 111 nongynecologic tumors. With OV632 no reactivity was found in carcinomas of the breast or the gastrointestinal tract. Cytologic preparations of malignant effusions of patients with ovarian cancer showed reactivity with OC125 in 32 of 35 cases, and OV632 with positivity in 34 of 35 cases. Mesothelial cells in reactive effusions were OC125 positive in 16 of 20 cases but never showed positivity with OV632. The authors conclude that for histopathology a combination of OC125 and OV632 offers high sensitivity (0.86) and specificity (0.89) for ovarian cancer. For cytology, OV632 is the most specific tumor marker available.

A modified ELISA technique for the titration of antibodies to polio virus as an alternative to a virus neutralization test.

An ELISA based on inhibition of antibody binding for the determination of antibodies to polio virus type I is described. F(ab1)2-fragments of bovine antibodies to polio virus type I are used as the capture antibody thus lowering the background staining. A good correlation was found between the poliovirus neutralizing antibody level and the antibody titers as determined by ELISA.

Malignant melanoma in fine needle aspirates and effusions. An immunocytochemical study using monoclonal antibodies.

The value of monoclonal antibodies (MAbs) for the immunodetection of keratin, vimentin and two melanoma-associated antigens recognized by NKI/C3 and NKI/Bteb for the diagnosis of malignant melanoma has been previously established on histologic preparations. In the present study, cytologic preparations from 20 fine needle aspirates and effusions from patients with malignant melanoma were evaluated using these antibodies. Twenty of 20 smears were negative for keratin, and 20 of 20 smears were positive for vimentin. Positivity for NKI/C3 was seen in 12 of 12 cases studied, and for NKI/Bteb in 12 of 13 cases. These results indicate that a panel of MAbs consisting of anti-keratin, anti-vimentin, NKI/C3 and NKI/Bteb is useful for a more accurate diagnosis of malignant melanomas on cytologic preparations. The expression of these antigens in melanoma cells in cytologic smears can be a valuable aid in the detection of primary (noncutaneous) and metastatic melanomas by fine needle aspiration.

Effects of iodized oil on trivalent oral polio vaccine in vitro.

Iodine deficiency can be effectively reversed by administration of iodized oil (IO). Since 1989, the WHO Expanded Programme on Immunization recommended delivery of oral IO along with vaccines, in appropriate situations. However, administration of IO at the same time as trivalent oral polio vaccine (TOPV) has not been recommended because of absence of studies addressing potential harmful effects of iodized oil on immuno-responses to TOPV. In this study an in-vitro cell culture system was used to measure possible adverse effects of IO on TOPV. The system itself was shown not to be influenced by either IO or a standard non-iodized oil (NIO). However, marked effects of IO on virus infectivity was measured when a 50% mixture of IO and TOPV was incubated for 48 h at 37 degrees C, as compared to incubation without IO. Clear differences were found in effects of IO on vaccines of different sources, suggesting differences in composition of these vaccines, e.g. in stabilizers. Principally Sabin 3 appeared susceptible to IO under the given extreme conditions. Pre-dilution of the IO-TOPV mixture prior to incubation clearly reduced the effects of IO on virus infectivity Inoculation of the IO/TOPV-mixture directly onto susceptible cells, a model approaching the in vivo situation, resulted in no detrimental effects on virus infectivity. Further studies are planned looking at interactions of iodized oil and TOPV in children at immunization contacts.

An enzyme-linked immunosorbent assay for the detection of mouse polyomavirus-specific antibodies in laboratory mice.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection and quantification of IgM and IgG serum antibodies to mouse polyomavirus (MPV). To evaluate the potential of this ELISA for the screening of laboratory rodents, serum samples from specific pathogen free (SPF) BALB/c RIVM mice, collected after experimental intraperitoneal infection with MPV, were tested by this assay. The results were compared with those obtained from the same sera in an immunofluorescence assay (IFA) and a haemagglutination inhibition assay (HIA). The ELISA proved to be the most sensitive of the 3 assays, allowing the detection of seropositive animals within 7 days post-infection and giving antibody titres that were about 4 to 8 times higher than those found in the IFA and HIA respectively. More than 5000 serum samples from non-infected specific pathogen free laboratory mice and 90 from 10 SPF N:NIH/RIVM mice experimentally infected with K-papovavirus, were negative in this assay, thus confirming the specificity of the ELISA.

Potency of veterinary rabies vaccines in The Netherlands: a case for continued vigilance.

Commercial rabies vaccines, used by veterinarians in the Netherlands, were collected for testing in the mouse potency test. Of the six vaccines tested, two were clearly below the minimal requirements for potency of 1.0 IU. Of these six vaccines the rabies virus glycoprotein (GP) and nucleoprotein (NP) contents were determined in an antigen competition ELISA. The GP content proved to correlate well with the potency found in the mouse potency test (r = 0.95, p < 0.01), whereas no such correlation was found for the NP content (r approximately 0, p > 0.05). After the manufacturers were told about the results, one of the two vaccines that did not comply with the requirements was withdrawn from the market. Measurement of the GP content of a second lot of the remaining vaccines indicated that sufficiently high levels of GP were present in all five. Additional in vivo testing in mice for efficacy against intracerebral challenge with the Dutch bat rabies virus EBL1-12 resulted in acceptable levels of protection with four of these five vaccines of the second lot. The data presented illustrate the need for continued potency evaluation of veterinary rabies vaccines in the Netherlands.

[Degree of protection against poliomyelitis of Dutch subjects born before 1945 and of allochthonous subjects in Utrecht, and the relationship to socioeconomic status]. / Beschermingsgraad tegen poliomyelitis van Nederlanders geboren vóór 1945 en van allochtonen in de stad Utrecht, en het verband met de sociaal-economische status.

In 1992 a seroepidemiological survey regarding the immune status for poliomyelitis was carried out amongst the population of the city of Utrecht: Dutch people born before 1945 and migrant workers and their families of all ages. Migrant workers and their families were well protected against poliomyelitis, using the WHO criteria (titre > or = I:8). The Dutch people born before 1945 were also well protected. Protection of Dutch people born before 1945 was better as their socioeconomic status was lower.

[Virological and serological aspects of the Dutch polio epidemic in 1992]. / Virologische en serologische aspecten van de Nederlandse polio-epidemie in 1992.

During the 1992 poliovirus type 3 outbreak in the Netherlands virological and serological investigations were conducted. No molecular epidemiological link was traced between poliovirus type 3 that caused the outbreak of poliomyelitis in the Netherlands and isolates from previous epidemics investigated. Serological neutralization assessments indicate that the inactivated poliomyelitis vaccine used in the Dutch national immunization schedule induces immunity to the causative agent.

[The value of cytological studies in nodular goiter: results in 495 patients]. / De waarde van cytologisch onderzoek bij nodulair struma: resultaten bij 495 patiënten.

The accuracy of clinical diagnosis and fine-needle aspiration biopsy (FNAB) was evaluated in a total of 495 patients of whom 183 were operated upon within 6 months after FNAB and 312 were not. Operated patients were divided into three subgroups with high, moderate or low suspicion of malignant neoplasms on clinical grounds. Histological examination revealed an overall malignant neoplasm rate of 23%. The rate, i.e. the positive predictive value, was 74% for the subgroup with high clinical suspicion, vs 14% and 10% respectively for the subgroups with moderate and low clinical suspicion. The sensitivity of a high clinical suspicion was 60% and the specificity 93%. The overall sensitivity of FNAB was 93% in the operated group and probably not less than 87% in all patients studied; specificity was 71% and 84% respectively for these groups. The overall positive predictive value of a positive cytology result (malignant or uncertain) was 48%. In the subgroups with moderate or low clinical suspicion which are more representative of a non-university setting, the average predictive value was 27%. In our opinion all patients in the group with high clinical suspicion need surgical treatment, regardless of the FNAB result; those with lower degrees of clinical suspicion and malignant or uncertain FNAB result should also undergo diagnostic surgical exploration.

[Poliomyelitis in The Netherlands, 1979-1991: immunity and exposure]. / Poliomyelitis in Nederland, 1979-1991: immuniteit en blootstelling.

An overview is presented of serological and virological studies on poliovirus immunization and circulation in the Netherlands, performed between 1979 and 1991. In this period, only three patients with poliomyelitis were notified. All had acquired the infection abroad. The vaccinations in the national immunization programme, using inactivated poliovirus vaccine, build a strong immunity. This can also be seen in age-stratified serological profiles of the Dutch population. In these surveys, persons from the time at which vaccination was offered have neutralizing antibodies. Older persons, especially those born between 1930 and 1945, sometimes lack antibodies. However, 85-90% of them show a rapid booster response upon vaccination, demonstrating immunological memory. Hence, they will be protected against poliomyelitis upon contact with wild poliovirus. Virological data show a regular import of poliovirus, especially in adoptive children tested on entry into the Netherlands, coming from developing countries. Nearly all other virus isolates in Dutchmen were related to import from such countries. None of the imported patients or other persons in whom poliovirus was detected spread the virus over the country. It demonstrates that as a rule the herd immunity of the well-vaccinated Dutch population is good. Exceptions occur, however, as demonstrated by the epidemics in 1978 and 1992. Large socio-geographic clusters of susceptible people who refuse vaccinations are not sufficiently protected.

Virologic control of monkeys used for the production of poliomyelitis virus vaccine.

Wild-caught or captive-bred cynomolgus monkeys (Macaca fascicularis) used at the National Institute of Public Health for the production of inactivated poliomyelitis virus vaccine are extensively controlled for the presence of antiviral antibodies in their sera. With relatively simple methods of segregation and hygienic measures it seems possible to keep the animals free of infections with certain viruses including Herpesvirus simiae and foamy viruses, which is of obvious importance for Public Health and for vaccine production.