High-risk human papillomavirus (HPV) types in patients with squamous intraepithelial lesions (SIL).

The aim of the paper was to determine the probability of joined occurrence of certain HPV types, particularly those with high oncogenic risk and histopathological (HP) findings (LGSIL and HGSIL, i.e., micro invasive and invasive carcinoma) as well as to find out to what extent either presence or absence of HPV can be identified in HP findings. The investigation was carried out on 48 patients. Based on a suspected colposcopy findings, Papanicolaou (Pap) smear and biopsy were performed and a histopathological analysis of the sample was carried out. A cervical smear was made on all the patients for HPV detection and typing. The results in the group with HPV, which showed histological diagnoses of LGSIL in 80% of cases, revealed numbers significantly higher with respect to the same summing up in the group where HPV was not detected (66.6%). HP findings of HGSIL in both groups were diagnosed in almost the same percentage and it should be taken into account that there were 6.7% of patients with Ca in situ in the group of HPV-positive patients. Therefore, it can be concluded that if a diagnosis of LGSIL or HGSIL, in particular, has been made on the basis of HP findings there is a great probability that it is a case of infection by one or more joined types of human papillomaviruses. The presence of virus specific genes in one of the stages of tumor development at the beginning of the infection indicates the viral etiology of tumors. The presence of HPV genome was not proved in 21% of patients with HGSIL. A multiple infection with different HPV types is more often found in patients with LGSIL than in those diagnosed with HGSIL. This demonstrates the selection of high oncogenic types and their persistence during the course of carcinoma progression.

Correlation between atypical colposcopy findings and detection of human papillomavirus (HPV) infection of the uterine cervix.

Reports on the detection of genome human papillomaviruses (HPV) in genital neoplasia differ to a great extent either in the overall prevalence or in the frequency of certain types. The aim of the study was to determine the correlation between the HPV infection and the occurrence of premalignant and malignant diseases of the uterine cervix and to investigate the ratio between clinical features and infection findings starting from the assumption that infection by human papillomaviruses is a key factor in the occurrence of premalignant and malignant disease of the uterine cervix. The investigation was carried out on 48 patients who formed the study group (Group I). Based on suspicious colposcopy findings, a Papanicolaou (Pap) smear and biopsy were performed and a histopathological analysis of the sample was carried out. A cervical smear was done on all the patients for HPV detection and typing. The patients in whom HPV infection was not found formed a control group (C Group). In spite of certain divergences it has not been proved that the ratio between colposcopy findings and HPV type has any statistical importance (chi2 = 3.305; p > 0.05). The distribution of Pap smear results did not shown a significant difference with respect to HPV type (chi2 = 0.105; p > 0.05). When the data are analyzed the diagnosis of low-grade squamous intraepithelial lesions (LGSIL) is evident in 20% of the HPV cases whereas it is significantly lower with respect to the group where HPV was not detected (42.5%). Histopathological (HP) findings of a high-grade squamous intraepithelial lesions (HGSIL) in both groups are diagnosed in approximately the same percentage while 6.7% of cancer in situ was registered in the group of HPV positive patients. Based on this it can be concluded that if a diagnosis of LGSIL or HGSIL in particular has been made on the basis of HP findings there is a great probability that the infection was due to one or more joined types of human papillomaviruses.

[The lipodystrophy syndrome and protease inhibitor therapy in HIV infection]. / Lipodistroficki sindrom i terapija inhibitorima proteaza kod HIV infekcije.

The accumulation of adipose tissue in the dorsocervical region is a typical finding in patients with intensive glycocorticoid function. This finding was described in numerous HIV infected patients. Combined antiretroviral therapy that included a protease inhibitor implied the suggestion that dorsocervical fat pad could be a consequence of protease inhibitor therapy. This is a case report of a patient who developed a similar changes a year after the beginning of protease inhibitor therapy.

Locally produced specific cytomegalovirus immunoglobulin for intramuscular use as a therapy in renal allograft recipients.

Immunomodulator, i.e. specific hyperimmune anticytomegalovirus immunoglobulin for intramuscular administration, produced in 1999 with the aim of prevention of CMVI, and the development of the disease, was for the first time applied in kidney transplant recipients in January 2000, in the Center for kidney transplantation at the Military Medical Academy. Therapy was administered in four cytomegalovirus (CMV)--seronegative kidney recipients from CMV-seropositive donors--the combination that in the majority of cases lead to the development of CMVI/disease resulting in transplant rejection. Patients received 0.2-0.3 ml/kg of cytomegalovirus immunoglobulin (CMVIG) 6 hours before the transplantation, and subsequently the same dose during the following 5 weeks. Simultaneously, they received ganciclovir in therapeutic doses adjusted according to creatine clearance during the first three post-transplantation months (2 weeks parenterally, the rest orally). Kidney transplant recipients tolerated well i.m. applied CMVIG without any adverse effects. Test result obtained from the Paul-Erlich Institute, Germany in 1999 spoke in favor of the quality of the first national CMVIG preparation.

[Detection of human papillomaviruses in cervical intraepithelial neoplasms]. / Otkrivanje virusa humanih papiloma u intraepitelinim neoplazijama grlica materice.

Over the period 1994-1998 1000 patients suffering from intraepithelial cervical lesions (SIL) were examined for the presence of Human Papilloma Virus (HPV) infection. Today it is completely acknowledged that certain types of these viruses play a key role in the onset and evolution of these diseases. The study showed that SIL of the cervix appears in very young women. The highest incidence was found in age groups 24-28 years (21.10%) and 29-33 years (19.10%). Thus, over 40% of the entire study group patients was under 34 years of age. Histological analysis of tissue samples showed that 79.30% of patients had lesions of low histological grade (LSIL), while in 20.70% of them the disease progressed to a high histological level (HSIL). Detection of Human Papilloma Virus Infection revealed negative results in 34.90% of patients, 17.80% were 6/11 positive (non-oncogenic type), and in 47.30% oncogenic types were found (16, 18, 31, 33). This finding in the LSIL group was exceptionally important since it influenced the approach to treatment. Oncogenic types of viruses were detected in 34.30% of LSIL lesions; it indicates a high progression potential of pathological changes.

[Effect of certain aspects of female sexual behavior on the development of cervical intraepithelial neoplasia]. / Uticaj nekih parametara sekusualnog zivota zene na pojavu intraepitelinih neoplazija grlica materica.

The paper presents results of investigation of certain parameters of female sexual activity and their effect on the appearance of squamous intraepithelial cervical lesions (SIL). This correlation was investigated in the context of Human Papilloma Virus (HPV) infection, in view of the role attributed to certain types of these viruses in the appearance and development of cervical SIL. Research was done on 1000 patients suffering from low histological grade (LSIL) or high histological grade (HSIL) intraepithelial cervical neoplasms. It transpired that such lesions were most frequent in women in the second, third and fourth decade of life, and that one third of pathological lesions was a function of age. Human Papilloma Virus infection was detected in 65% of patients. The frequency of HPV negative results or presence of non-oncogenic types of viruses (6 and 11) was significantly higher in LSIL type lesions, while the frequency of detection of oncogenous HPV types (16, 18, 31 and 33) was significantly higher in more severe stadiums of the disease. Of the investigated parameters of sexual activity, early onset of such activity and several sexual partners proved to be significant. The number of parturitions and abortions did not appear to be significant risk factors for the onset and development of these diseases.

Isolation of a coronavirus from kidney biopsies of endemic Balkan nephropathy patients.

Endemic Balkan nephropathy (EBN) is a kidney disease of unknown etiology limited to Bulgaria, Rumania and former Yugoslavia. Primary kidney tissue cultures were established as explants from tissue obtained at operations from 5 EBN patients with urinary tract tumors. Four out of the five biopsy specimens on extended culture incubation at 33 degrees C yielded a coronavirus virus (EBNV) which was cytopathogenic for human fibroblast and Vero cells. In cells inoculated with EBNV, cytoplasmic immunofluorescence was found using antisera for human coronaviruses OC43 and 229E as well as the porcine transmissible gastroenteric virus and avian (chicken) bronchitis virus. In neutralization tests, EBNV failed to react with antisera to these viruses. Using hyperimmune serum raised with EBNV, positive cytoplasmic immunofluorescence was seen with cells infected with OC43, 229E, TGV and significantly with the kidney tissue of the biopsy specimens from the EBN patients. A screen for neutralizing antibody using the EBN virus revealed that 87.2% of EBN patients on dialysis were positive, also 74% of people from an endemic area were also positive, while only 13.5% from outside were positive. It is suggested that a coronavirus is involved in the etiology of the disease and that humans are an incidental host of a coronavirus zoonosis.

[Elevated Epstein-Barr virus antibodies in patients with Hodgkin's disease]. / Nalaz povisenog titra antitela prema Epstajn-Barovom virusu kod osoba obolelih od Hockinove bolesti.

INTRODUCTION: Some studies of Hodgkin's disease support the concept that the disease may be due, directly or indirectly, to a common infectious agent, an infection acquired in late rather than early childhood being associated with an increased risk of oncogenesis. The Epstein-Barr virus is the leading candidate as one of these causative agents, because of its oncogenic properties in the laboratory and its association with two human malignancies, African Burkitt lymphoma and nasopharyngeal carcinoma. METHODS: We studied 49 patients with Hodgkin's disease. The patients were grouped according to the histologic type, clinical symptoms and immune state. The control group of 140 subjects was selected among healthy people. The antibodies against viral capsid antigen were measured with immunoperoxidase test, antibodies to nuclear antigen with anticomplement immunofluorescent test, and antibodies to early antigen with immunofluorescence method. RESULT: We found that all patients had antibodies against viral capsid antigen and nuclear antigen. We found an elevated titers for viral capsid antigen in 69% of patients, early antigen in 41% and nuclear antigen in 55% of patients. The incidence of elevated titers (> or = 320 for viral capsid antigen and > or = 40 for early antigen) and nuclear antigen was higher in patients than in control group; the differences were statistically significant. Also, the geometric mean of early viral capsid and of nuclear antibody titers in patients were significantly higher than that in control group (p < 0.01). DISCUSSION: The possible role of Epstein-Barr virus in Hodgkin's disease has been long investigated in epidemiological studies and the finding of Epstein-Barr antibody has been currently supported by the detection of genomic Epstein-Barr virus in diagnostic cells in some cases of Hodgkin's disease. Hodgkin's disease varies in prevalence, morphologic findings and association with Epstein-Barr virus in different parts of the world. Hodgkin's disease in Yugoslavia and its relationship to Epstein-Barr virus has not yet been studied. In conclusion, our results indicate that elevated titers of antibody against antigens associated with Epstein-Barr virus exist in patients with Hodgkin's disease. Whether this finding reflects a direct role of Epstein-Barr virus or whether this activity is a marker of the effect of a more fundamental factor, is not yet clear.

[Detection of Epstein-Barr virus DNA in malignant lymphomas]. / Detekcija DNK Epstein-Barr-ovog virusa u malignim limfomima.

The etiology of malignant lymphomas is unknown, but certain evidence imply the possibility of Epstein-Barr virus connection to this disease. The presence of Epstein-Barr viral DNA in 95 patients with malignant lymphomas (49 patients with Hodgkin's disease and 46 patients with non-Hodgkin's lymphomas) was investigated by method of in situ hybridization. Viral DNA was proved in 30.53% patients with malignant lymphomas: in 38.78% of patients with Hodgkin's disease and 21.74% patients with non-Hodgkin's lymphomas. Those facts point out that Epstein-Barr virus is one of the possible carcinogens involved in those tumors growth.

Stimulatory effect of low-power density He-Ne laser radiation on human fibroblasts in vitro.

Cultures of human embryonic fibroblasts in vitro were subjected to helium-neon laser single and double irradiation to investigate the influence of low-energy laser irradiation on fibroblast proliferation. Mean increase in the cell number values of irradiated cells were compared with increase values of non-irradiated control samples of fibroblasts. He-Ne laser was used as a coherent source of monochromatic radiation at 632.8 nm, and Petri-dishes with cultured fibroblasts were irradiated in way to receive radiation of energy doses of 0.5; 1; 1.5 and 2J/cm2. Single He-Ne laser irradiation exhibited a significant stimulation effect on human fibroblast proliferation in cell-culture.

[Viral hepatitis C. Personal experience with diagnostic, monitoring and epidemiologic studies]. / Virusni hepatitis C. Nasa iskustva u dijagnostici, pracenju i epidemioloskim ispitivanjima.

In the period from 1991 to 1993, 18 patients with the acute viral hepatitis type C were treated and followed up--13 men and 5 women, the average age of 42 years. The group of 6 patients (4 men and two women) with the "old" proven liver cirrhosis, whose etiology was unknown for 20 years, was analyzed. The investigations showed that the acute viral hepatitis type C usually began with the mild subjective disorders. The half of the patients did not have either jaundice or hepatomegaly, only half of them recover, and the first cases of cirrhosis could have been expected almost as early as a year after the beginning of illness. The developed liver cirrhoses remained compensated for years. About 58% of patients got infected parenterally, and the rest of them could have gotten infected in other manner. ELISA test showed great reliability in proving the antibodies against the viral hepatitis type C in the confirming the diagnosis of illness.

[Clinical manifestations of infectious erythema in adults]. / Klinicko ispoljavanje infektivnog eritema kod odraslih.

The infectious erythema is usually childhood disease associated with rash and caused by parvovirus B19. At the beginning of 1993., at the Clinic for infectious and tropical diseases of the Military Medical Academy 36 patients were treated for this disease, the average age 21 years. The prodromal phase of illness lasted approximately 2.9 days, the elevated temperature 5.2 days, and 17 patients had temperature above 39 degrees C. The rash was usually maculo-papullous and lasted about 6 days. Four patients had the recurrence of rash. The polyarthralgia appeared for short in six patients and in one patient lasted longer than 4 months. The mild anemia during infectious erythema was observed in 18 patients. IgM antiparvo B19 antibodies were proven in serum in 91.7%, and IgG antibodies in 58.3% of patients.

[Personal experience in the treatment of chronic viral hepatitis B with recombinant interferon B alfa-2]. / Nasa iskustva u lecenju hronicnog virusnog hepatitisa B alfa-2 rekombinantnim interferonom.

Twelve patients were treated with alpha-2 recombinant interferon during 4 months. Patients were given daily dose of 3 million units three times a week. Therapeutic effect expressed as the percentage of HBeAG seroconversion or by the loss of antibodies for the core antigen in IgM fraction and by the core antigen loss from hepatic tissue, was achieved in 41.6% of patients. Corticosteroids, administered before interferon, could improve therapeutic effect. Better response to therapy was observed in patients with higher serum transaminase levels and with histopathologically confirmed chronic hepatitis. Predictive value of each immunological parameter of therapeutic effect requires further study.

[Chlamydia trachomatis and acute pelvic inflammatory disease]. / Chlamydia trachomatis i akutna pelvicna inflamatorna bolest.

The incidence of Chlamydia trachomatis infection in women with acute pelvic inflammatory disease has been studied. Chlamydia trachomatis was isolated in 20 (35.71%) of 56 examined women. In all women with positive isolation, the infection was also confirmed serologically.

[Detection of parvovirus B19 in the blood of patients using DNA hybridization]. / Primena DNK hibridizacije za detekciju parvovirusa B19 u serumu bolesnika.

DNA assay was used in detection of parvovirus B19. The sera of 63 patients were examined and the presence of DNA virus was found in two samples.

[Chlamydia trachomatis and Reiter's syndrome]. / Chlamydia trachomatis i Reiterov sindrom.

Results of the study of incidence of chlamydia trachomatis infection in patients with Reiters syndrome are presented. Chlamydia trachomatic was isolated from the uretral smear in 12 (34.28%) of 35 patients with Reiter's syndrome. In the group of patients with other rheumatologic diseases Chlamydia trachomatis was isolated in 2 (5.13%) of 39 patients. In all patients with negative isolation, infection was confirmed serologically also and in some patients with negative isolation it was also proved.