Cytomegalovirus disease as a possible etiologic factor for early atherosclerosis.

A group of 284 patients who underwent orthotopic heart transplantation between April 1986 to June 1991 and who were followed up for at least five years was analyzed in this paper. Patients were divided into three groups according to the presence or absence of cytomegalovirus infection or disease: patients without infection, patients with serologycaly proven infection and patients with cytomegalovirus disease. The analysis of survival was performed with respect to all major factors that influence survival: age and sex of a donor and a recipient, number of rejection episodes, perioperative ischemic time and pulmonary vascular resistence. A recipient's age was shown to be a significant factor. Patients who experienced at least one episode of cytomegalovirus disease had significantly worse long-term survival compared to those with the infection only or without the infection. That difference was caused by the increased incidence of coronary atherosclerosis, which caused deaths in patients with a previous episode of cytomegalovirus disease. A possible mechanism responsible for this phenomenon is discussed.

Helicobacter pylori and gastric cancer in Croatia.

The seroprevalence of Helicobacter pylori infection was studied in a population from two areas of Croatia with significantly different average gastric cancer (GC) cumulative incidence and mortality rates. In a random sample of 456 blood sera from both areas, which was tested with the ELISA Helicobacter pylori-antibody test, 48.8% of people in the north and 53.3% in the south of the country were found to be infected. The difference between the two areas in the seroprevalence of the infection was not statistically significant, nor did their populations differ in age, sex, educational background, smoking habit or wine consumption. Our results do not point to any association between the prevalence of Helicobacter pylori infection and the level of cumulative incidence and GC mortality levels.

Helicobacter pylori: in vitro induction of resistance to azithromycin.

Helicobacter pylori resistance to macrolides is possibly an important factor for the failure of macrolide therapy for H. pylori infection. The aim of this study was to assess the propensity of H. pylori to develop in vitro resistance to azithromycin. In 73 clinical isolates taken from patients before starting antimicrobial therapy of H. pylori infection, MIC was determined using an agar dilution method (Müller-Hinton agar with 7.5% unlysed horse blood, pH = 7.2, at 35 degrees C, during 72 h in a humid microaerobic atmosphere). Each strain was first cultivated at half minimal inhibitory concentration (MIC) then in doubling concentrations until growth arrest. All experiments for induction of resistance were performed on the same media, incubation temperature, atmosphere and time of MIC determination. MIC interpretative standards for sensitivity, intermediate sensitivity and resistance of H. pylori to azithromycin were < or = 2, 4 and > or = 8 mg/l, respectively. Of 73 strains, 5 died during the experiments, and in the remaining 68 strains, serial passage with increasing azithromycin concentrations resulted in the development of resistance in 19 (26.9%) strains. Two strains had an MIC of 16 mg/l azithromycin. Thirty-three (48.5%) strains kept the same MIC or doubled their MIC, 16 (23.5%) strains had 4- to 16-fold MIC but still remained sensitive, 2 resistant strains had 128-fold MICs and 17 resistant strains had increased their MICs more than 128 times. Seventeen highly resistant strains (MIC > 128 mg/l) were kept frozen at -70 degrees C for 3 months in a brain-heart infusion broth with 15% glycerol. MIC was assessed again to determine the stability of resistance. Eleven strains kept MICs > 128 mg/l, 2 became sensitive and 1 intermediate, but reverted easily, after only 2 passages, to an MIC of > 128 mg/l azithromycin. Although macrolides are very active against H. pylori, the propensity to develop resistance in a high proportion of strains has a clear impact on the choice of the right combinations of macrolides with other agents as well as the dosage of the macrolide antibiotics.

[Seroprevalence of Helicobacter pylori infection in health personnel in 3 hospitals in Zagreb]. / Seroprevalencija infekcije Helicobacterom pylori u zdravstvenih djelatnika triju zagrebackih bolnica.

By this study we wanted to investigate the seroprevalence of H. pylori infection in 175 health care workers of three Zagreb city hospitals. The obtained results were compared with those of 2492 volunteer blood donors. The influence of age, education, socioeconomic status and length of service at specific hospital working places were investigated in relation to the frequency of H. pylori seropositivity. The blood samples were tested by commercial kits of immunoenzyme assay (ELISA) and complement fixation (CF), according to manufacturers instructions. The mean seroprevalence of infection was 58.6% in the group of blood donors and 53.7% in the group of health care workers (NS). Statistically significant difference was found between physicians (29%) and all other health care workers: nurses (58.6%; p < 0.005), laboratory technicians (60.6%; p < 0.005), clerical workers (66.6%; p < 0.005) and auxiliary workers (82.6%; p < 0.001). Concerning the age, the infection seroprevalence was higher in workers aged more than 40 years than in those younger, and that difference was of statistical significance among nurses and laboratory technicians. Physicians under 29 yrs were of the lowest seropositivity (14.8%). Among health care workers with less than 20 working years, physicians expressed the lowest rate of infection (17.9%) in comparison with nurses (48.5%) and laboratory technicians (53.3%). In all health care workers with more than 20 working years there was significant increase of infection prevalence, particularly among nurses. The employees in gastrointestinal endoscopy laboratories were more often serologically positive than medical workers in other medical departments (58.3% versus 35.0%; p < 0.05).

[Distribution of Helicobacter pylori infection in the adult population of Croatia]. / Rasprostranjenost infekcije s Helicobacter pylori u odrasloj populaciji Hrvatske.

The study of the distribution of Helicobacter pylori infection was carried out among the population of Croatia aged between 20 and 70 years, in three areas of Croatia (central, northern, southern). For the detection of seroprevalence of this infection the ELISA test for IgG antibodies was used on a random sample of 3,082 serum samples. The testing showed an average rate of seroprevalence in Croatia of 60.4% (95% CI 58.7-62.1%). Higher infection rates were observed in older population of Croatia. These rates ranged from 51.6% in the third decade of life, to almost 70% in the sixth decade. In male subjects the average rate was 58.9% and in female subjects it was 65.9%. The difference was not statistically significant. The results of this study showed that distribution of this infection was not consistent in all the studied areas of Croatia. While the Helicobacter pylori infection prevalence was almost identical in the central area and in the northern counties of Croatia, 58.4% and 59.5% respectively, it showed statistically significant difference in the south, being 71.3% (chi(2) = 25.884, P < 0.001). An inconsistent distribution of this infection in Croatia was indicated also by standardized infection rates, which were 59 in the central area, 61 in the northern and 71 in the southern areas.

Total body irradiation with or without lung shielding for allogeneic bone marrow transplantation.

From June 1986 to June 1990, 64 patients with leukaemia (25 acute myelogenous leukaemia, 21 acute lymphoblastic leukaemia and 18 chronic myeloid leukaemia) undergoing marrow transplantation were randomized to receive cyclophosphamide (CY) and fractionated total body irradiation (TBI) without lung shielding (n = 33) or CY and fractionated TBI with lung shielding (n = 31, control group) as conditioning. Patients conditioned with TBI without lung shielding received a significantly higher total lung dose compared with the control group (p less than 0.0001). The 3-year leukaemia-free survival for patients receiving TBI without lung shielding is 54 +/- 18% versus 51 +/- 18% for patients receiving TBI with lung shielding (p = ns). There was no significant difference in the probability of leukaemia relapse (22 +/- 18% for TBI without lung shielding versus 24 +/- 18% for control group; p = ns). The probability of interstitial pneumonitis is 15 +/- 14% for TBI without lung shielding and 5 +/- 5% for TBI with lung shielding (p = ns). A higher incidence of lung fungal infection (15 versus 3%) and interstitial pneumonitis (12 versus 3%) has been documented in patients receiving TBI without lung shielding compared with the control group. The results indicate that higher radiation dose to the lung did not increase antileukaemic efficacy of TBI but seemed to be associated with the increased pulmonary toxicity.

[Legionnaires' disease in Yugoslavia (an epicritical review of patients)]. / Legionarska bolest u nas (epikriticki pregled bolesnika).

A review of patients with Legionnaires' disease hospitalized in our Clinic from the first cases recorded in 1978 up to now has been given. The diagnosis was confirmed by indirect immunofluorescent method in 23 patients with pneumonia, using antigen and method of the Center for Disease Control Biological Products Division, Atlanta, Georgia, USA (Dr Wilkinson). Most of the patients (16) were sporadic cases and twice as less cases were from two epidemics (7). Two patients among sporadic cases developed a very severe form of the disease during the immunosuppressive therapy after kidney transplantation. Clinical, epidemiological and laboratory data of 10 patients hospitalized and treated during the last three years (1986-1988) were analyzed in details. Two thirds of these patients were above 40 years of age and the youngest one was 29 years old. Except the advanced age no other firm disposable factor was found in patients belonging to sporadic cases. In cases from epidemics the source of infection was probably water from water-pipes i.e. hotel devices (bathrooms, douches, drinking water, air-conditioning units, water used in kitchen for cooking etc). All patients recovered after a longer symptomatic and antibiotic treatment. Erythromycin and rifampicin were applied the most frequently. In some patients treatment with chloramphenicol was effective.

Is there an association between fetal viral infection and fetal malformation? I. Detection of specific IgM antibodies in the serum of malformed fetuses.

Determinations of IgG and IgM antibodies specific for cytomegalovirus (CMV), herpes simplex virus (HSV1), herpes simplex virus (HSV2), varicella-zoster virus (VZV), rubella, echo, Coxsackie and morbilli viruses were performed in 20 sera from malformed fetuses. Demonstration of a fetal infection by increased fetal serum IgM permits linkage to a detected fetal malformation. In parallel, 14 maternal sera and 17 amniotic fluid samples were examined. Laser nephelometry (a quantitative method) was used for the determination of IgM and IgG class immunoglobulins. None of the fetal sera were found to contain IgM class antibodies specific for the viral antigens studies. While IgM CMV-specific antibodies were present in one maternal serum, the specific IgM was absent in the fetus. The absence of specific IgM antibodies appears to warrant the conclusion that the malformed fetuses were uninfected by any of the above viruses. IgM antibodies were detected in two fetal sera by quantitative methods. The IgM antibodies present in two fetuses probably were generated in response to some other introduced antigen.

[Detection of IgG and IgM antibodies to herpes simplex virus type 1 and type 2 in human serum using an immunoenzyme method (ELISA) and the complement fixation reaction]. / Detekcija IgG i IgM antitijela za herpes simplex virus tip 1 i tip 2 u ljudskim serumima pomocu imunoenzimne metode (ELISA) i RVK.

On the basis of borderline optical density values (OD) in an enzyme-linked immunosorbent assay (ELISA) resulting from comparative testing of this method with complement fixation reactions (CF), determination was made of a set criteria for negative, weakly positive and positive results of IgG and IgM antibody detection of Herpes simplex type 1 (HSV 1), respectively type 2 (HSV 2). Of the 192 examined specimens by ELISA, 69.2% and 49.5% IgG HSV 1 and HSV 2 antibodies were found respectively. The number of sera containing IgM HSV 1 od HSV 2 antibodies was low (5.7%), since in the majority of cases the relapsing form of infection was involved. The sensitivity of ELISA to IgG in comparison with CF was slightly higher with the HSV 1 antigen (69.2:68.2%), and apparently lower with HSV 2 (49.5:28.2%). ELISA permits partial differentiation to be made between HSV 1 and HSV 2 antibodies due to a greater degree of antigen purity compared with the unpurified antigen used in CF. In fact, CF is known not to possess the sensitivity necessary to differentiate between HSV 1 and HSV 2 antibodies. For diagnostic purposes, ELISA findings could be more appropriately expressed quantitatively, in corresponding measurement units.

Cytomegalovirus mononucleosis in children compared with the infection in adults and with Epstein-Barr virus mononucleosis.

We report clinical and laboratory findings in 11 previously healthy children with cytomegalovirus (CMV) mononucleosis and compare them with those of 18 adults with CMV mononucleosis and with those of 22 age-matched children with Epstein-Barr virus (EBV) mononucleosis. Exudative pharyngitis was more common in children whereas prolonged fever was more common in adults. Prominent lymphadenopathy and exudative pharyngitis, however, were less frequent in children with CMV mononucleosis than in those with EBV mononucleosis. Nevertheless, children with CMV mononucleosis are more likely to resemble those with EBV mononucleosis than adults with CMV mononucleosis.

Mononucleosis-like syndrome associated with a multisystem Coxsackie virus type B3 infection in adolescence.

We describe a severe multisystem Coxsackie virus type B3 infection in a previously healthy 14-year-old girl who presented with a mononucleosis-like syndrome (MS). Initial observations included a prominent cervical lymphadenopathy, exudative pharyngitis and leucocytosis with atypical lymphocytosis. At the end of the 2nd week of illness the patient developed meningoencephalomyelitis and haemolytic anaemia. Subclinical myocarditis was also recorded. Prolonged hepatitis recrudescing at the time of recovery coincided with serological evidence of a reactivated Epstein-Barr virus infection. The diagnosis was based on a significant rise in serum antibody titres against Coxsackie virus type B3, using the neutralization test. Intrathecal synthesis of antibodies to Coxsackie virus type B3 was also demonstrated. Generalized Coxsackie virus infections in adolescence are rare and an MS has not, to our knowledge, been associated with Coxsackie virus type B3 infection.