Patterns of antihypertensive medication use in kidney transplant recipients.

AIM: This study analyzed the prevalence of hypertension and the pattern of antihypertensive treatment before and after kidney transplantation. PATIENTS AND METHODS: The prevalence of hypertension and the class and daily dosage load of antihypertensive medications were analyzed in 116 patients before kidney transplantation and 1, 6, and 12 months after transplantation (67.2 % males, mean age 45.9 ± 11.4 years). Two patients died and eight had the allograft explanted, leaving 106 patients in the final analysis. Blood pressure (BP) was recorded on the day of transplantation and at every follow-up; it was considered uncontrolled at values > 130/80 mmHg. RESULTS: The prevalence of uncontrolled BP was significantly reduced after kidney transplantation (63.2 % before transplantation vs. 54.7, 41.5, and 25.5 % at the 1­, 6­, and 12-month follow-up, respectively, p < 0.001 for all). The number of prescribed antihypertensives did not change significantly during the follow-up (1.96 ± 1.03 before transplantation vs. 2.01 ± 0.88, 1.71 ± 0.78, and 1.73 ± 0.73 at the 1­, 6­, and 12-month follow-up, respectively, p > 0.05 for all). There was a significant decrease in antihypertensive drug load during the follow-up (1.08 ± 1.3 end of the study vs. 2.05 ± 2.32 before transplantation, p < 0.008). Before kidney transplantation, angiotensin-converting enzyme (ACE) inhibitors were most commonly prescribed (52.8 %), while after surgery ß­blockers gained prevalence (59.4-63.2 %). Mean arterial pressure decline correlated with an improvement of graft function. CONCLUSION: The prevalence of uncontrolled BP and the antihypertensive drug dosage load reduced significantly after kidney transplantation. ß­blockers were used more frequently than ACE inhibitors after kidney transplantation.

The antinociceptive efficacy of morphine-ketamine-magnesium combination is influenced by the order of medication administration.

OBJECTIVE: Ketamine and magnesium, both N-methyl-D-aspartate (NMDA) receptor antagonists, enhance the antinociceptive effects of opioid analgesics in different animal models of pain, as well as in humans. This study aimed at evaluating whether magnesium sulphate added to morphine-ketamine combination produces a higher level of analgesia. MATERIALS AND METHODS: Analgesic activity was assessed by tail-immersion test in male Wistar rats (200-250 g). RESULTS: Magnesium sulphate (0.5-60 mg/kg, s.c.) and ketamine (5-30 mg/kg, i.p.) administered alone did not produce any effect. Magnesium sulphate (5 and 60 mg/kg) and ketamine (5 and 30 mg/kg) increased the antinociceptive effect of morphine (2.6 mg/kg, i.p.). Magnesium sulphate (5 mg/kg) increased the antinociceptive effect of the morphine (2.6 mg/kg)-ketamine (2.5 or 5 mg/kg) combination when magnesium sulphate was added to morphine after, and not before ketamine. It is also demonstrated that magnesium sulphate prolonged the duration of the antinociceptive effect of the morphine-ketamine combination. Low dose of morphine (2.6 mg/kg), ketamine (5 mg/kg) and magnesium sulfate (5 mg/kg) given together did not cause motor impairment that could be verified on a rotarod test. The antinociceptive effect of the triple combination was readily antagonized with naloxone (3 mg/kg, s.c.), a nonselective antagonist of opioid receptors, indicating that the effect is mediated via opioid receptors. CONCLUSIONS: This study revealed that the efficacy of the morphine-ketamine-magnesium sulphate combination in tail-immersion test in rats is influenced by the order of medication administration; a higher level of activity is demonstrated only when ketamine is added to morphine before magnesium sulphate.

A synergistic interaction between magnesium sulphate and ketamine on the inhibition of acute nociception in rats.

OBJECTIVE: Magnesium is an endogenous voltage-dependent NMDA receptor-channel blocker and ketamine is a non-competitive NMDA receptor antagonist. Magnesium may potentiate the effect of ketamine in analgesia and anaesthesia, but may also interact in an opposing manner. This study aimed at evaluating type of the interaction between magnesium sulphate and ketamine administered systemically in rats with an acute nociceptive pain (tail-immersion test). MATERIALS AND METHODS: Analgesic activity was assessed by tail-immersion test in male Wistar rats (200-250 g). The distal 5 cm of the tail was immersed in a warm water bath (55 ± 0.5°C) and the time for tail-withdrawal was measured as response latency. RESULTS: Magnesium sulphate (2.5-30 mg/kg, s.c.) and ketamine (2.5-30 mg/kg, i.p.) administered alone did not produce any effect. However, significant antinociception (synergistic interaction) was revealed at the following doses of ketamine: magnesium sulphate of 5:5 mg/kg, 2.5:5 mg/kg and 10:5 mg/kg. The effect was not dose-dependent, and a greater response was obtained when ketamine was administered before magnesium sulphate. CONCLUSIONS: This study revealed that (1) magnesium sulphate and ketamine given alone were not effective against acute nociceptive pain in rats, but (2) a combination of both drugs resulted in synergistically inhibited nociception, (3) which occurred only at selected low doses and proportions of the medications in a combination and (4) suggested the importance of the order of drug administration.

Serum interleukin-17 & nitric oxide levels in patients with primary Sjögren's syndrome.

BACKGROUND & OBJECTIVES: The interleukin (IL)-17 producing T-helper cells have been linked to pathogenesis of autoimmunity and mostly investigated in rheumatoid arthritis (RA). In this study we tested the IL-17 levels, as well as the levels of nitric oxide (NO) as possible IL-17-induced product, in patients with primary Sjögren's syndrome (pSS), an intricate and complex chronic autoimmune disorder of exocrine glands. METHODS: Serum IL-17 levels and nitrite concentrations determined in patients with pSS (n=30) were compared with the values obtained in patients with RA (n=10) and healthy controls (n=15). The values obtained for IL-17 in pSS patients were also associated with the patients' clinical characteristics, particularly the rheumatoid factor (RF) and total antinuclear antibodies (tANA) levels. RESULTS: Serum concentrations of IL-17 were significantly (P<0.01) higher in patients with pSS (12.9 ± 28.0 pg/ml) as compared to those obtained in healthy individuals (0.2 ± 0.6 pg/ml), but not as high as the values obtained for the patients with RA (34.5 ± 56.2 pg/ml). The mean IL-17 levels were significantly (P<0.05) higher in the pSS patients positive for rheumatoid factor (20.3 ± 33.3 pg/ml) than in RF-negatives (0.3 ± 0.6 pg/ml). Mean serum concentrations of IL-17 were also higher in antinuclear antibody (ANA)-positive samples (19.8 ± 33.5 pg/ml) in comparison to ANA-negative sera (1.1 ± 3.1 pg/ml) (P<0.05). The NO levels also showed elevated values in both pSS and RA patients, as compared to the healthy controls, since mean nitrite levels in patients with pSS and RA were 38.2 ± 29.2 µM and 41.7 ± 21.1 µM, respectively, while those in healthy controls were significantly lower, at 19.2 ± 10.5 µM. INTERPRETATION & CONCLUSIONS: The findings of this study showed that there was increased IL-17 and NO production in patients with primary SS, especially if they had associated elevated rheumatoid factor and antinuclear antibody values.

Analysis of disease activity, functional disability and articular damage in patients with juvenile idiopathic arthritis: a prospective outcome study.

OBJECTIVES: We longitudinally studied outcomes of patients with juvenile idiopathic arthritis (JIA) using the Childhood Health Assessment Questionnaire (CHAQ) for physical disability and the Juvenile Arthritis Damage Index for articular (JADI-A) and extra-articular damage (JADI-E), and we correlated them with various disease activity variables. METHODS: Eighty-seven patients with JIA were included in the prospective follow-up study with median age 14 years (4.6-18.0), disease duration 5.2 years (2.0-18.9) and follow-up of 4.0 years (2.0-5.2). Besides JADI-A and JADI-E, and the assessment of active joints count, joints with limited mobility, ESR, CHAQ and radiographic damage of joints was also done. A correlation analysis of CHAQ and JADI with various disease activity variables was performed. RESULTS: The patient's distribution of JIA subtypes were polyarticular (32), systemic onset (13), oligoarticular (31), and enthesitis related arthritis (11). After a follow-up period, 46% patients had active disease compared to 83% patients at baseline (p<0.01). The CHAQ disability index improved over baseline, while radiological damage (p<0.001) and JADI-A and JADI-E scores worsened (p<0.001). CHAQ and JADI significantly correlated with the majority of disease activity variables. CHAQ DI was significantly higher in the patients with coxitis (p<0.01) and wrist arthritis (p<0.001). The most pronounced deterioration in articular damage (JADI-A) was observed in patients with sJIA (3.69 at baseline vs. 5.69 at study endpoint). CONCLUSIONS: The improvement of functional disability (CHAQ DI) was observed over the course of the disease, whereas radiological joint damage, JADI-A and JADI-E scores worsened. Children with systemic JIA, wrist arthritis, coxitis and prolonged active disease are at higher risk of progression of severe disability.

Fluorescence spectroscopy of an in vitro model of human cervical neoplasia identifies graded spectral shape changes with neoplastic phenotype and a differential effect of acetic acid.

BACKGROUND: The clinical utility of spectroscopic methods for the diagnosis of cervical cancer is limited by significant inter-patient variation in the spectroscopic properties of the cervix. Improved understanding of the contributions of the components of cervical tissue to the observed spectra would therefore be helpful in the development of spectroscopic approaches to the study of cervical disease in vivo. METHODS: In this study, we used organotypic epithelial raft culture as an in vitro model system to analyse the fluorescence properties of the surface squamous epithelium specifically. The spectrum of cervical dysplasia was modelled by producing rafts lined by primary human keratinocytes (PHKs) and the HaCaT, SiHa and CaSki human keratinocyte cell lines and fluorescence emission spectra were recorded at a wide range of excitation wavelengths. RESULTS: Statistically significant differences in spectral shape were identified between the different rafts at excitation wavelengths between 250nm and 310nm. A graded, differential effect of acetic acid on fluorescence intensity was also observed, consistent with the visible effects of acetic acid on clinical examination at colposcopy. CONCLUSION: These data suggest that the development of neoplastic changes in the squamous epithelium of the cervix are associated with alterations in its fluorescence properties and that the application of acetic acid has a demonstrable effect on these properties. Identification of these alterations may aid the discrimination of cervical lesions in vivo.

Fentanyl analogs: structure-activity-relationship study.

Fentanyl is the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics. This study was aimed to review the structure-activity-relationship (SAR) of fentanyl analogs substituted in the position 3, or 4 of the piperidine ring. Pharmacological results show that the groups in position 3 of the piperidine ring, which are larger than methyl, severely reduce the analgesic potency compared to fentanyl. It is likely that the steric factor alone (i.e. voluminosity of the group and cis/trans isomerism), rather than the polarity and/or chemical reactivity, plays a crucial role in the analgesic potency of this series. Although the duration of action, in general, does not depend on the stereochemistry, longer action of the most potent 3-alkyl fentanyl analogs such as cis-3-methyl- and cis-3-ethyl fentanyl, is more likely influenced by pharmacodynamic, rather than pharmacokinetic variables. Also, it is possible that the introduction of a functional group such as 3-carbomethoxy reduces the duration of action by altering pharmacokinetic properties. SAR findings obtained by evaluating the neurotoxic effects of fentanyl analogs substituted in the position 3 of the piperidine ring parallel the SAR findings on analgesia in regard to potency and duration of action. This might suggest that similar receptors are involved in producing both antinociceptive and neurotoxic effects of these drugs. It appears that both the potency and the duration of action in the series of fentanyl analogs substituted in position 4 of the piperidine ring is influenced only by the steric requirement and not by the chemical nature of the substituent.

A LED-LED-based photoplethysmography sensor.

A high sensitivity, low power and low cost sensor has been developed for photoplethysmography (PPG) measurement. It uses standard light emitting diodes (LEDs) as both light emitter and detector, pulse-based signal conversion techniques instead of the classical analogue-to-digital convertors (ADCs) and a general purpose microcontroller for the implementation of measurement protocol. The main advantages of the proposed approach are that it leads to better spectral sensitivity, increased and adjustable resolution, reduction in cost, dimensions and power consumption, and it avoids the need for expensive and precise operation amplifiers, ADCs and other external components. The basic sensing configuration presented uses only two I/O pins and two LEDs and is capable of detecting the PPG signal from a finger or toe. It is then very simple to extract the vital signs such as heart rate and heart rate variability from such a signal. The basic configuration can easily be expanded to include a pulse oximeter for the determination of oxygen saturation (SpO(2)) by the addition of only two more LEDs. The proposed technique is also suitable for a wide range of other photometric applications.

Adaptation and validation of a telephone questionnaire--Serbian version for case detection of rheumatoid arthritis and spondyloarthropathy (multicentric Eular study).

OBJECTIVE: To adapt and validate a telephone questionnaire for case detection of rheumatoid arthritis (RA) and spondyloarthropathies (SpA) in the Serbian population. METHODS: A questionnaire, developed by the French Society of Rheumatology and successfully tested in France, was adapted to the Serbian language using a cross-cultural adaptation process. It was validated in 150 patients: 50 with RA, 50 with SpA and 50 with degenerative rheumatic disorders. They were recruited from Institute of Rheumatology in Belgrade, hospital registry, years 2001 and 2002. The questionnaire validity was assessed in reference to clinical diagnosis and ACR 1987 and ESSG 1991 classification criteria. A logistic regression model was used for RA-control and SpA-control comparison to identify the set of items that best discriminates these groups. RESULTS: Cross-cultural adaptation of the Questionnaire was successfully achieved, verifying its equivalence with the original (semantic, idiomatic, experiential, conceptual). According to the logistic regression, two items selected for RA provided 92.1% agreement when using either clinical diagnosis or ACR classification criteria as a standard. SpA-control comparison included five items providing 96.8% agreement with clinical diagnosis and four items providing 94.1% agreement with ESSG criteria. Results of the present study are similar to those found in the French study. CONCLUSION: Validation results of the telephone questionnaire, translated and adapted to the Serbian language, confirm that it can be used as a detection tool for RA and SpA cases in the population of Serbia, whose diagnoses would have to be further confirmed.

Neurovascular stalk of the superficial sural flap: human fetus anatomical study.

BACKGROUND: The neurovascular stalk of the superficial sural flap, which is the most frequently used, is composed of the lesser saphenous vein, the sural nerve, and the median superficial sural artery. However, it has many variations. This is very important for its application in the reconstruction of soft-tissue defects. The aim of the authors' research was to detect the presence of the superficial sural blood vessels and to investigate their relationships with the sural nerve and the lesser saphenous vein. METHODS: The study group consisted of 42 fetal lower extremities. Fetuses were fixed in 10% formalin and their blood vessels were injected with Micropaque solution (barium sulfate). RESULTS: The median superficial sural artery was detected in 83.3 percent of the cases, whereas the sural nerve and lesser saphenous vein were detected in all cases. The median superficial sural artery was located lateral to the medial cutaneous sural nerve and sural nerve, whereas the lesser saphenous vein was located medially. CONCLUSIONS: All three superficial sural arteries (medial, median, and lateral) were detected in fetuses with different gestational ages. The median superficial sural artery was the most frequently detected one and had the constant relationship with the other elements of the neurovascular stalk of the superficial sural arteries.

[Antibiotics in the prevention of the surgical site infection in orthopedic surgery]. / Antibiotici u prevenciji infekcije hirurske rane u ortopedskoj hirurgiji.

Surgical site infection is an actual problem of orthopaedic surgery. Despite considerable efforts that have been done during last several decades (e.g. improvements in surgical techniques, preoperative preparation of the surgical site, infection-control practice, use of preventive antibiotics) surgical site infection still affects about 0.5-2% of patients after closed fracture surgery or insertion of prosthetic devices. They are associated with substantial morbidity and mortality. The adherence to the principles of rationale preventive antibiotic therapy has an important role in the prevention of the surgical infection. In addition, it is well known that inappropriate use of antibiotic promote development of resistance, superinfections and increase the cost of the treatment. This paper focuses on the basic principles of rational use of antibiotics, i.e. appropriate selection of drug, dose, and duration of treatment in the prevention of surgical site infections in orthopaedic surgery.

Epidemiology of end-stage renal disease and current status of hemodialysis in Yugoslavia.

Maintenance hemodialysis (HD) in Yugoslavia started in the sixties and followed the dialysis trends in the Western Europe. However, in the last decade the development of renal replacement therapy (RRT) slowed down. In this report the epidemiology of ESRD from 1997-1999 and the survey of the status of HD treatment in Yugoslavia in 1999 are presented. Epidemiological data are obtained by the annual center questionnaires (response rate: 92.6 -94.2%). The survey of HD status is based on a specific questionnaire and covered 2108 patients (65%). At the end of 1999 there were 56 RRT centers in Yugoslavia treating 3939 patients: 3232 (82%) patients by HD, 248 (6.3%) by peritoneal dialysis, and 459 (11.7%) living with transplanted kidney. In a three year period, incidence of ESRD ranged from 108-128 pmp, point prevalence from 435-463 pmp and mortality rate from 20.7-17.9. Numerous refugee patients were treated over the last 10 years. Main causes of ESRD were glomerulonephritis (30%); Balkan nephropathy represented 11% and diabetic nephropathy 7% of all primary renal diseases. Cardiovascular and cerebrovascular diseases were the most common causes of death of RRT patients. Most centers are overcrowded and HD machines are worn out. Mean Kt/V was 1.19+/-0.08, mean URR% 58.8+/-7.4. The shortage of drugs prevented adequate management: 83% of HD patients had hemoglobin level less than 100 g/L but only 10.3 -17.8% were treated with rHuEpo; 64.5% of patients had phosphate levels higher than 1.7 mmol/L but only 33.5% used phosphate binders; 47% of patients had hypertension despite the antihypertensive therapy. The prevalence of hepatitis B remained unchanged (about 14%) in HD population during the last three years, but the prevalence of anti-HCV positive patients decreased (31-23%). In conclusion, there is a well developed dialysis service in Yugoslavia but insufficient conditions for adequate treatment.

The Serbian version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Serbian language of the parentís version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Serbian CHAQ-CHQ were fully validated with 3 forward and 1 backward translations. A total of 139 subjects were enrolled: 79 patients with JIA (30% systemic onset, 28% polyarticular onset, 6% extended oligoarticular subtype, and 36% persistent oligoarticular subtype) and 60 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Serbian version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Antinociceptive activity of the novel fentanyl analogue iso-carfentanil in rats.

A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful antinociceptive drugs. In this study, the newly synthesized fentanyl analogue 3-carbomethoxy fentanyl (iso-carfentanil) was compared to fentanyl for its antinociceptive activity (tail-immersion test) in rats. It was revealed that the introduction of a 3-carbomethoxy group in the piperidine ring of fentanyl skeleton reduced the potency and shortened the duration of action of the parent compound, i.e., fentanyl. The antinociceptive potency of 3-carbomethoxy fentanyl is influenced mainly by the steric factor (voluminosity of the carbomethoxy group and the cis/trans isomerism), while the chemical nature of the group is probably irrelevant. This is in agreement with SAR studies of other 3-substituted fentanyl analogues. In contrast to potency, the duration of action is not affected by cis/trans isomerism. It is assumed that the time course of action of 3-carbomethoxy fentanyl is influenced by the nature of the carbomethoxy group. Since the potency and the duration of action of this novel antinociceptive compound are interesting from the aspect of SAR studies and have potential promise for clinical application, 3-carbomethoxy fentanyl deserves to be extensively evaluated.

Prevalence of rheumatoid arthritis in Belgrade, Yugoslavia.

OBJECTIVE: To determine the prevalence of chronic arthritis with special reference to rheumatoid arthritis. METHOD: A cross-sectional study was performed during the years 1990 and 1991 in a randomly selected sample of the urban population of Belgrade. RESULTS: Out of 2184 participants, > or = 20 yr old, surveyed by questionnaire, 756 (34.6%) reported peripheral joint complaints. Of those with complaints, 621 (82.1%) agreed to undergo detailed examination. Arthritis was diagnosed in four men (one had rheumatoid arthritis and three had spondylarthropathy with peripheral arthritis) and 11 women (three had rheumatoid arthritis, one had B27-positive polyarthritis and seven had undifferentiated chronic arthritis). The prevalence of chronic arthritis in the adult population was 0.69% (0.35% for men and 1.05% for women). The prevalence for rheumatoid arthritis was 0.18% (0.09% for men and 0.29% for women). Re-examination of 15 individuals with chronic arthritis 3 yr later showed changes in diagnosis only in those patients who at baseline examination had undifferentiated chronic arthritis. CONCLUSION: According to the results obtained, the urban population of Belgrade is among populations with a low prevalence of rheumatoid arthritis.

[Serum and urinary interleukin-6 levels in patients with primary glomerulonephritis]. / Nivo interleukina sest u serumu i urinu bolesnika s primarnim glomerulonefritisom.

Several studies have suggested that the measurement of urinary interleukin-6 (IL-6) is a helpful tool for diagnosis and monitoring the progression of glomerulonephritis. The aim of this study was to determine if IL-6 level might reflect the histological type of glomerular lesions. We performed a prospective study of 43 patients who underwent renal biopsy in our hospital. There were 35 male and 8 female patients with median age of 30.5 years (range 19-50). Included among these were 13 cases of IgA nephropathy, 11 cases of membranoproliferative glomerulonephritis, 6 cases of poststreptococcal glomerulonephritis, 6 cases of mesangial proliferative glomerulonephritis, 5 cases of membranous nephropathy and 2 cases of C3 nephritis. IL-6 was measured by ELISA (Lucernachem, Switzerland). IL-6 was not detected in the serum and rine of 15 healthy controls. IL-6 was elevated in the urine of 30 patients with different histological types of glomerular lesions (range 3.7 to 433.3 pg/ml) but was not detected in the urine of remaining 13 patients. The presence of IL-6 in the urine in absence of raised serum IL-6 suggests that urinary IL-6 was produced by the kidney. We have concluded that urinary IL-6 level can be considered as a marker of glomerulonephritis but not one that is very specific for any particular histological type of primary glomerulonephritis. Thus, the urinary IL-6 level is not a useful tool in the differential diagnosis of primary glomerulonephritis. We need further studies to determine whether urinary IL-6 level could by considered for monitoring of disease activity and therapy.

[Angioimmunoblastic lymphadenopathy with dysproteinemia and hypothyreosis]. / Angioimunoblastna limfadenopatija s disproteinemijom i hipotireoza.

A patient with angioimmunoblastic lymphadenopathy with disproteinemia is presented. The diagnosis is made on the basis of lymph node hystology and laboratory findings of typical immunologic aberrations. The patient had signs of developed primary hypothyreosis with cardiac failure at the same time. The two diagnsis were made in the late stages of diseases, two years after the first findings of generalised lymphadenopathy and clinical signs of hypothyreosis, with developed complications in the form or cardiac, respiratory and renal failure. The disease had terminated lethaly before the pathohystologic diagnosis was known.

Isolation of a Puumala-like virus from Mus musculus captured in Yugoslavia and its association with severe hemorrhagic fever with renal syndrome.

An outbreak of severe hemorrhagic fever with renal syndrome (HFRS) occurred in 1988 in Pozarevac, Serbia, Yugoslavia. The disease was diagnosed in 4 children and 1 adult, and 1 of the children died. Rodents were captured from the same area and virus isolation attempted. A hantavirus, POZ-M1, was isolated from lung tissues of hantavirus antigen-positive Mus musculus. Serology and restriction enzyme digestion of polymerase chain reaction-amplified segments from this virus showed that it was a strain of Puumala (PUU) virus, the causative agent of nephropathia epidemica. While Clethrionomys glareolus is the major rodent host for PUU virus, these results suggest that M. musculus may also play an important role in harboring and transmitting PUU-like viruses. The serologic association of this virus with patients with severe HFRS reaffirms that PUU-like viruses may cause severe disease in addition to the generally mild form normally associated with nephropathia epidemica.

Hemorrhagic fever with renal syndrome in Yugoslavia: epidemiologic and epizootiologic features of a nationwide outbreak in 1989.

A nationwide epidemic of hemorrhagic fever with renal syndrome (HFRS) occurred in Yugoslavia in 1989. Sera from 609 hospitalized patients, from all six Republics (Bosnia and Hercegovina, Croatia, Macedonia, Montenegro Serbia, Slovenia) and two Provinces (Kosovo and Vojvodina), who had signs and symptoms suggestive of HFRS, and sera and lung tissues from 544 small mammals belonging to 13 species were studied for evidence of hantavirus infection. Of the 226 patients with serologically confirmed HFRS, 182 resided in Bosnia and Hercegovina or in Serbia. The severity of disease differed from region to region, with an overall fatality of 6.6% (15/226). Patients from southern Yugoslavia tended to have more severe disease and exhibited two types of antibody patterns, while approximately equal numbers of clinically severe and mild cases of HFRS were registered in central Yugoslavia, where four types of antibody patterns were found. Two of these antibody patterns suggested the existence of hantaviruses which are antigenically distinct from those reported to date. Two seasonal peaks of disease, one during the summer and the other in late autumn, were found. Hantaviral antibodies and/or antigens were detected most often in the yellow-necked mouse (Apodemus flavicollis) (88/189), the wood mouse (Apodemus sylvaticus) (28/146), the striped field mouse (Apodemus agrarius) (10/64), the bank vole (Clethrionomys glareolus) (36/63), the house mouse (Mus musculus) (14/29), and the Norway rat (Rattus norvegicus) (14/21). Five other species of rodents and insectivores were infrequently infected.

Characterization of Dobrava virus: a Hantavirus from Slovenia, Yugoslavia.

Small mammals were collected in natural foci of hemorrhagic fever with renal syndrome (HFRS) in Slovenia, Yugoslavia, and a hantavirus was isolated from the lungs of an Apodemus flavicol lis captured in Dobrava village. This new isolate, Dobrava virus, was compared with representative strains of the Hantavirus genus by serological and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. It was found by cross immunofluorescent and enzyme-linked immunosorbent assays that antigenic properties of Dobrava virus were different from those of other hantaviruses. The RNA of this virus was successfully amplified with hantavirus genus reactive primer sets by reverse transcriptase polymerase chain reaction (RT-PCR); however, PCR-RFLP analysis of the amplified product was shown to be unique among those of the known hantaviruses, further indicating that Dobrava virus represents a new hantavirus serotype.