Overnight S100B in Parkinson's Disease: A glimpse into sleep-related neuroinflammation.

Calcium-binding protein B (S100B), a primary product of astrocytes, is a proposed marker of Parkinson's Disease (PD) pathophysiology, diagnosis and progression. However, it has also been implicated in sleep disruption, which is very common in PD. To explore the relationship between S100B, disease severity, sleep symptoms and polysomnography (PSG) findings, overnight changes in serum S100B levels were investigated for the first time in PD. 17 fully treated, non-demented, moderately advanced PD patients underwent PSG and clinical assessment of sleep symptoms. Serum S100B samples were collected immediately before and after the PSG. Results are shown as median [interquartile range]. Night and morning S100B levels were similar, but uncorrelated (rs=-0.277, p=0.28). Morning S100B levels, as opposed to night levels, positively correlated with the Unified Parkinson's Disease rating scale (UPDRS) subsections I and II (rs=0.547, p=0.023; rs=0.542, p=0.025). Compared to those with overnight S100B reduction, patients with overnight S100B elevation had higher H&Y scores (2.5 [0.87] vs. 2 [0.25], p=0.035) and worse total Pittsburgh Sleep Quality Index (PSQI) and Parkinson's Disease Sleep Scores (10 [3.2] vs. 8 [4.5], p=0.037; 92.9 [39] vs. 131.4 [28], p=0.034). Correlation between morning S100B levels and total UPDRS score was strengthened after controlling for total PSQI score (rs=0.531, p=0.034; partial rs=0.699, p=0.004, respectively). Overnight S100B variation and morning S100B were associated with PD severity and perceived sleep disruption. S100B is proposed as a putative biomarker for sleep-related neuroinflammation in PD. Noradrenergic-astrocytic dysfunction is hypothesized as a possible mechanism underlying these findings.

Prevalence of sleepiness in a group of Brazilian lorry drivers.

OBJECTIVE: To determine the prevalence of sleepiness in a group of Brazilian lorry drivers. STUDY DESIGN: Cross-sectional study. METHODS: This study used a self-administrated questionnaire and the Epworth Sleepiness Scale (ESS). The questionnaire included questions regarding demographic features, professional data, sleep habits, night-time symptoms, excessive daytime sleepiness and history of previous automobile accidents. RESULTS: Four hundred and thirty-eight male drivers, aged 34.2+/-9.5 years (mean+/-SD), were included in the study. The mean number of hours spent driving each day was 9.2+/-2.6h, compared with 4.5+/-2.3h for the night shift. The median distance covered weekly was 1,200 km (range 70-6,000 km). The most common sleep complaints were insomnia (26.6%), loud snoring (45%) and witnessed apnoea (7.6%). Eighty-six of 392 (22%) drivers reported falling asleep while driving, and 11 (2.8%) subjects indicated falling asleep daily or almost daily. One hundred and seventy-one drivers (39%) had been involved in a traffic accident, and 21 of 128 drivers (16.4%) indicated sleepiness as a possible contributing factor. The ESS was higher than 10 points in 120 (28%) of the interviewees. CONCLUSIONS: Sleepiness is a prevailing symptom in lorry drivers and is probably related to accidents.

Gatifloxacin 200 mg or 400 mg once daily is as effective as ciprofloxacin 500 mg twice daily for the treatment of patients with acute pyelonephritis or complicated urinary tract infections.

The efficacy and safety of two oral dosing regimens of gatifloxacin were compared to ciprofloxacin in the treatment of complicated urinary tract infection in a randomised, double-blind multi-centre trial. One thousand one hundred and twenty-three adult patients with complicated urinary tract infection (70%) or pyelonephritis (30%) were initially enrolled, 1122 were treated. Of these, 824 were included in a modified ITT population: gatifloxacin 200 mg (274 patients) or 400 mg (280 patients) once daily or ciprofloxacin 500 mg twice daily for 5-14 days (269 patients). Bacteriological and clinical responses were assessed 7-9 days after the end of treatment (EOT) and 4-6 weeks post-treatment (end of study visit, EOS). The bacteriological response rates per patient at EOT in the gatifloxacin 400 mg, gatifloxacin 200 mg and ciprofloxacin groups were 77% (207/269), 78% (208/268) and 73% (190/259), respectively. At EOS they were slightly lower: 70% (184/262), 71% (176/248) and 69% (174/252), respectively. The clinical responses at EOT were 69% (190/277), 70% (190/273) and 65% (174/266). At EOS they were 71% (193/273), 70% (182/259) and 74% (190/258). The overall eradication rates of initial pathogens at EOT and EOS were 85.3% and 88.4% in the gatifloxacin 400 mg group; 84.1 and 90.1% in the gatifloxacin 200 mg group and 85.1 and 91.4% in the ciprofloxacin group. Both oral regimens of gatifloxacin were as effective as that of ciprofloxacin. All treatment groups showed a similar safety profile, nausea being the most frequently reported adverse event.

Virulence characteristics of Escherichia coli strains causing asymptomatic bacteriuria.

BACKGROUND: The objective of this study was to examine the expression of Escherichia coli virulence-associated factors among the strains isolated from a group of women with a history of recurrent urinary tract infections (UTIs), in whom asymptomatic bacteriuria (ABU) was detected at follow-up, and from a group of children without a history of previous UTI, in whom ABU was detected during the screening. Possible differences between the virulence potential of these strains were investigated. MATERIALS AND METHODS: Hemolysin production, the ability to adhere to Buffalo green monkey cell line and hemagglutination (HA) ability of the ABU-associated E. coli strains were tested. E. coli strains isolated from patients with acute recurrent UTIs served as a comparison. RESULTS: The well-known low virulence of strains isolated from patients with ABU was demonstrated. In contrast to strains isolated from recurrent uncomplicated UTIs, the ABU-associated strains were mostly nonhemolytic (75%), nonadherent (70%) and lacked HA ability (61%). HA ability was significantly more common among the strains isolated from children without a history of UTI than among the strains isolated from women with recurrent UTIs (chi2 = 9.97, p < 0.01), whereas the adherence and hemolytic abilities did not differ between the two ABU groups. CONCLUSION: A further prospective study is needed to determine whether the HA ability is the predictor of subsequent symptomatic UTI.

Comparative analysis of azithromycin and clarithromycin efficacy and tolerability in the treatment of chronic prostatitis caused by Chlamydia trachomatis.

A total of 123 patients, older than 18 years of age, with symptoms of chronic prostatitis and inflammatory findings as well as the presence of Chlamydia trachomatis confirmed by DNA/RNA DIGENE hybridization method in expressed prostatic secretion or in voided bladder urine collected immediately after prostatic massage, were examined. The patients were randomized to receive a total of 4.5 g of azithromycin for 3 weeks, given as a 3-day therapy of 1 x 500 mg weekly or clarithromycin 500 mg b.i.d. for 15 days. Patients' sexual partners were treated at the same time. Clinical and bacteriological efficacy were evaluated 4-6 weeks after the end of therapy. In the group of patients with chronic chlamydial prostatitis the eradication rates (azithromycin 37/46, clarithromycin 36/45) and the clinical cure rates (azithromycin 32/46, clarithromycin 32/45) were not significantly different with regards to the administered drug (p > 0.05). In the group of patients with asymptomatic chlamydial prostatitis the eradication rates (azithromycin 11/16, clarithromycin 10/15) were not significantly different with regards to the administered drug (p = 1.00, OR = 1.1).

[Antimicrobial therapy of urinary tract infections]. / Antimikrobno lijecenje infekcija mokracnog sustava.

Urinary tract infections (UTIs), according to localization of infection, can be subdivided into urethritis, cystitis, prostatitis and pyelonephritis, according to type of infection into symptomatic, asymptomatic, acute (first or single), recurrent, chronic, complicated and uncomplicated. Clinical symptoms of cystitis and leukocyturia are sufficient reason for early initiation of a three-day empirical antimicrobial therapy of acute uncomplicated cystitis in young women. Urine culture should be performed prior to the initiation of antimicrobial therapy in pregnant women, diabetics, recurrent UTIs, in case of unsuccessful prior treatment and in patients with pyelonephritis. All symptomatic UTIs should be treated, as well as asymptomatic bacteriuria in pregnant women, diabetics, preschool children and prior to urologic-gynecologic surgery. In complicated UTIs it is especially important to determine and try to eliminate or at least put under control the factors that complicate UTIs. Antimicrobial therapy of UTIs includes fluoroquinolones, co-trimoxazole, betalactam antibiotics, aminoglycosides and nitrofurantoin, tetracyclines, macrolides, and azalydes in case of sexually transmitted diseases caused by Chlamydia trachomatis and Ureaplasma urealyticum. Cystitis is treated for 1, 3 or 7 days, asymptomatic bacteriuria 3-7 days, uncomplicated pyelonephritis 10-14 days, bacterial prostatitis 4-8 weeks, and chronic nonbacterial prostatitis 2-4 weeks. Recommended therapy for chronic and complicated UTIs is 7-14 days only in relapses and reinfections, and in some patients it can last for several weeks, up to 6 months. Chemoprophylaxis in recurrent uncomplicated UTIs should be employed for at least 6 months.

Duration of clinical symptoms in female patients with acute urethral syndrome caused by Chlamydia trachomatis treated with azithromycin or doxycycline.

One hundred fifty-one female patients with acute urethral syndrome caused by Chlamydia trachomatis were examined. First, patients were divided into two groups, those with clinical symptoms present < 3 weeks before the start of treatment, and those with clinical symptoms > or = 3 weeks prior to the beginning of therapy. Then patients were further divided into groups and randomized to receive azithromycin once daily in a single dose of 1.0 g or 500 mg once daily for 6 days, or to receive doxycycline 100 mg b.i.d. for 14 days or 100 mg b.i.d. for 7 days (8 study groups in all). Clinical and bacteriological efficacy was evaluated 3 weeks after the end of therapy. In the group of patients with disease symptoms lasting for 3 weeks or longer, the eradication and clinical cure rates were significantly higher after administration of azithromycin in a dose of 1x500 mg/6 days than after a single dose of 1.0 g (p<0.01), and after administration of doxycycline 2x100 mg/14 days than by using doxycycline 2x100 mg/7 days (p<0.05).

Azithromycin and doxycycline in the treatment of female patients with acute urethral syndrome caused by Ureaplasma urealyticum: significance of duration of clinical symptoms.

One hundred ninety-two female patients with acute urethral syndrome caused by Ureaplasma urealyticum were examined. First, patients were divided into two groups: those with clinical symptoms present for less than 3 weeks before the start of treatment and those with clinical symptoms 3 weeks or longer before the beginning of therapy. The patients were then further divided into groups and randomized to receive azithromycin once daily in a single dose of 1 g or 500 mg once daily for 6 days, or to receive doxycycline 100 mg b.i.d. for 14 days or 100 mg b.i.d. for 7 days (eight study groups in all). Clinical and bacteriological efficacy were evaluated 3 weeks after the end of therapy. In the group of patients with disease symptoms lasting for 3 weeks or longer, eradication and clinical cure rates were significantly higher after the administration of azithromycin at a dose of 1 x 500 mg/6 days than after a single dose of 1 g (p < 0.001).

National and local antibiotic policies in Central and Eastern Europe.

To assess the antibiotic policies of Central European countries, we performed an overview of antibiotic stewardship, prescription habits and antibiotic prescription regulatory procedures. Since most Central European countries have had centralized health care and drug policies, the situation 10 years after decentralization is surprising. Only 3 of 10 Central European countries have some regulation of prescription of antibiotics, only 4 restrict some antibiotics, only 5 have hospital and only 3 national antibiotic policies. In all but 3 countries physicians can prescribe quinolones and/or 3rd generation oral cephalosporins as first-line antibiotics. Information on local and national antibiotic policies in Central and Eastern European countries is given including prescription guidelines for antibiotic use in community and hospital.

Levofloxacin in the empirical treatment of patients with suspected bacteraemia/sepsis: comparison with imipenem/cilastatin in an open, randomized trial.

An open, randomized, multinational, multicentre study was conducted to compare the efficacy, safety and tolerability of levofloxacin 500 mg twice daily with imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized adult patients with clinically suspected bacteraemia/ sepsis. Levofloxacin patients could change from iv to oral administration after a minimum of 48 h iv treatment if clinical signs and symptoms of sepsis had improved. The primary efficacy analysis was based on the clinical and bacteriological response at clinical endpoint. A total of 503 patients were randomized and 499 included in the intent-to-treat population. The per-protocol population comprised 287 patients with bacteriologically proven infection. Clinical cure rates at clinical endpoint in the intent-to-treat population and per-protocol population were 77% (184/239) and 89% (125/140), respectively, for levofloxacin and 68% (178/260) and 85% (125/147), respectively, for imipenem/cilastatin. At follow-up, the cure rates in the per-protocol population were 84% for levofloxacin and 69% for imipenem/cilastatin. The 95% confidence interval for both populations showed that levofloxacin was as effective as imipenem/cilastatin. A satisfactory bacteriological response was obtained in 87% (96/110) of levofloxacin patients and 84% (97/116) of imipenem/cilastatin patients at clinical endpoint. Adverse events possibly related to the study drug were reported in 74 (31%) levofloxacin patients and 79 (30%) imipenem/cilastatin patients. There were no clinically appreciable differences between the treatment groups. Levofloxacin 500 mg twice daily, either iv or as sequential iv/oral therapy, was as effective and well tolerated as imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized patients with suspected bacteraemia/sepsis.

Methylprednisolone anaphylaxis.

The exacerbation of asthma is a problem frequently encountered by emergency physicians. In addition to oxygen and beta adrenergic agonists, oral and intravenous corticosteroids are increasingly being used to alleviate bronchospasm and to prevent recurrence of dyspnea. Methylprednisolone sodium succinate has been advocated as an intravenous adjunct in the treatment of asthma. We present the case of a steroid-dependent, 17-year-old male asthmatic, who experienced anaphylaxis, with respiratory arrest, within minutes of receiving intravenous methylprednisolone. Our patient rapidly responded to respiratory support and epinephrine. Methylprednisolone-induced anaphylaxis is reviewed.

Urinary tract infections in HIV disease.

HIV-positive patients are liable to acquire opportunistic infections. Their liability to acquire other common infectious conditions is less frequently reported. In order to determine the frequency of urinary tract infections (UTI) in HIV-positive patients, we performed a retrospective analysis. The control group was formed from patients with community acquired pneumonia. We reviewed charts of 96 HIV-positive patients and of 314 patients in the control study group. The analysis has shown that patients with HIV had a UTI more frequently than the controls. Besides the difference in the frequency, we observed the difference in the etiology. Enterococci were the most frequent isolates in patients with HIV disease, whereas Escherichia coli was most frequently isolated in the controls. These facts should be taken into consideration when treatment of a UTI with suspected bacteremia in AIDS patients is initiated.

Azithromycin: single 1.5 g dose in the treatment of patients with atypical pneumonia syndrome--a randomized study.

An open comparative study was undertaken in order to assess the efficacy and safety of a single dose of azithromycin in the treatment of community-acquired atypical pneumonia. A total of 100 adult patients with atypical pneumonia syndrome were randomized to receive 1.5 g of azithromycin as a single dose, or 500 mg once daily for 3 days. The presence of Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, and Legionella pneumophila infection was diagnosed by serological tests. Control clinical examinations were performed 72 h, 10-12 days and 4 weeks after treatment initiation. Among 96 patients (48 in each group) who were evaluable for clinical efficacy M. pneumoniae infection was confirmed in 24, C. pneumoniae in nine, C. psittaci in five, C. burnetii in six, and L. pneumophila in five. Forty-seven patients (97.9%) in each group were cured. Side effects were observed in two patients in the single-dose group, and one patient in the 3-day group. In conclusion, a single 1.5 g dose of azithromycin may be an alternative to the standard 3-day azithromycin regimen in the treatment of outpatients with atypical pneumonia syndrome.

Azithromycin in the treatment of pneumonias caused by Chlamydia spp: a retrospective study.

A retrospective study was undertaken in order to compare the efficacy and safety of azithromycin and doxycycline in the treatment of pneumonias caused by Chlamydia spp. Patients with radiologically confirmed pneumonia and positive complement fixation test for chlamydial infection who were hospitalized in the University Hospital of Infectious Diseases, Zagreb during the years 1989-1992 were reviewed. Among them, 83 were treated with azithromycin, given in a total dose of 1.5 g over 5 days (500 mg once daily at day 1 followed by 250 mg at days 2-5, 60 patients) or 3 days (500 mg once daily, 23 patients). Twenty-two patients were treated with doxycycline (100 mg b.i.d. for 10 days). Treatment groups were comparable with respect to age, sex, and severity of signs and symptoms of illness. All the patients were cured. There were no differences in duration of fever after treatment initiation between patients treated with azithromycin (whether pretreated with beta-lactam antibiotics or not) and doxycycline (p > 0.05). In addition, 3- and 5-day azithromycin courses were equally effective (p > 0.05). Both drugs were well tolerated, and only two patients treated with azithromycin reported nausea. It may be concluded that in the treatment of pneumonias caused by Chlamydia spp. azithromycin is as effective and well tolerated as doxycycline.

[Bacteremia and sepsis in patients hospitalized at the Dr. Fran Mihaljevíc Clinic for Infectious Diseases in Zagreb 1987-1991]. / Bakteriemija i sepsa u bolesnika hospitaliziranih u Klinici za infektivne bolesti "Dr. Fran Mihaljevic" u Zagrebu od 1987. do 1991. godine.

A total number of 836 episodes of bacteremia and fungemia were examined in 823 hospitalized patients in the University Hospital of Infectious Diseases "Dr Fran Mihaljevic" Zagreb from the beginning of 1987 to the end of 1991. Twenty-five percent of them were nosocomial bacteremias and 5% were polymicrobial bacteremias. The most frequently isolated causative agents were Salmonella spp. (26%), Escherichia coli (17%), Streptococcus pneumoniae (11%) and Staphylococcus aureus (8%). There were 34% of gram-positive bacteremias. The increased frequency of nosocomial bacteremias caused by coagulase-negative staphylococci was recorded. The frequency of coagulase-negative staphylococci strains resistant to gentamicin and Klebsiella spp. strains resistant to cefotaxime was increased. Shock was present in 19% of episodes. Relation between septic shock occurrence and causative agent of bacteremia was not proved. Mortality in patients with bacteremia was 13%, and total mortality was 20%. The outcome of the disease was in direct relation with causative agent of bacteremia. The initial empiric antimicrobial therapy was prolonged in 91% of episodes of bacteremia after blood culture results were known.