Survival of Huntington’s disease patients in Serbia: longer survival in female patients

The objective of this study was to estimate probability of survival of Huntington’s disease (HD) patients in Serbia as a function of CAG repeat length and selected demographic variables. This follow-up study was carried out at the Institute of Neurology, Clinical Centre of Serbia, Belgrade, 1982–2004. The study group consisted of 112 HD patients. The significant inverse correlation was found between CAG repeat length and age at onset of HD (r = −0.732, P = 0.001) and age at death (r = −0.760, P = 0.001). The cumulative probabilities of survival in a five, ten, fifteen, and twenty-years’ period were 90.9, 63.2, 10.3 and 4.5%, respectively. Higher survival probabilities were registered in female patients, as well as in those with older age at onset and lower number of CAG repeat length (≤46). The Cox regression analysis showed that significantly poorer outcome of HD in our population was related to younger age at onset (HR-hazard ratio = 1.9; P = 0.047), and larger CAG numbers (HR = 2.4; P = 0.071). The female sex was statistically significantly associated with longer survival (HR = 0.4; P = 0.007). These data might be of some importance for further exploration of natural history and prognosis of HD.     

Cerebrospinal fluid findings in patients with symptoms suggesting chronic Lyme borreliosis

BACKGROUND: Patients with non-specific long-lasting symptoms such as headache, concentration disturbances, and vertigo and who have positive serum borrelial antibody titres are often assumed to have chronic Lyme borreliosis. Because of the possibility that they may have central nervous system involvement they are frequently treated with courses of i.v. ceftriaxone. We assessed central nervous system involvement by examining cerebrospinal fluid samples in a group of such patients. PATIENTS AND METHODS: Adult patients who qualified for the study had non-specific symptoms suggesting central nervous system involvement for longer than six months (but without overt clinical signs of such involvement) and positive serum borrelial antibody titres and/or erythema migrans prior to the onset of symptoms. Cerebrospinal fluid was examined in all patients. RESULTS: None of the 77 patients included in the study (median duration of symptoms 18 months) had pleocytosis and there was no isolation of Borrelia burgdorferi sensu lato from cerebrospinal fluid. Mildly elevated protein concentration and intrathecal borrelial IgG antibody synthesis were demonstrated in 16 (21%) and 7 (9.1%) patients, respectively. CONCLUSIONS: In patients with non-specific long-lasting symptoms attributed to Lyme borreliosis but with the absence of overt clinical signs suggesting central nervous system involvement, the findings of cerebrospinal fluid examination are usually in the normal range. Routine treatment of such patients with i.v. ceftriaxone is not to be encouraged.     

Procalcitonin levels in patients with Lyme borreliosis

BACKGROUND: Serum and cerebrospinal fluid (CSF) procalcitonin levels were assessed and compared for different groups of patients with Lyme borreliosis. PATIENTS AND METHODS: 50 adult patients with Lyme borreliosis, referred to our department from March to June 2001, were included in this prospective study. Patients were divided into three groups. The first group consisted of 20 consecutive patients with typical solitary erythema migrans, representing early localised Lyme borreliosis, the second group comprised 20 patients with early disseminated Lyme borreliosis (10 with multiple erythema migrans and 10 with neuroborreliosis), and 10 patients with acrodermatitis chronica athrophicans represented the group with chronic Lyme borreliosis. Blood specimens were taken from all patients included in the study, but CSF samples were restricted to those with disseminated and chronic Lyme borreliosis. The serum and CSF procalcitonin levels were determined utilizing the LUMI PCT (an immunoluminometric assay using two antigen-specific monoclonal antibodies). RESULTS: Serum and CSF procalcitonin levels were in normal range in the large majority of patients. The levels of serum procalcitonin did not differ in the three groups of patients with Lyme borreliosis (p = 0.5006). The corresponding values for patients with solitary erythema migrans (early localised Lyme borreliosis), early disseminated Lyme borreliosis, and chronic Lyme borreliosis were 0.26 (0.11-0.43), 0.22 (0.10-0.67), and 0.28 (0.13-0.66) microgram/ml, respectively. Moreover, procalcitonin levels in CSF were also low and comparable for patients with multiple erythema migrans (median 0.38, range 0.24-0.54 microgram/ml), neuroborreliosis (median 0.16, range 0.10-0.47 microgram/ml), and acrodermatitis chronica athrophicans (median 0.30, range 0.15-0.45 microgram/ml). The differences were not statistically significant (p = 0.7579). CONCLUSIONS: In the large majority of patients with Lyme borreliosis procalcitonin values are within normal range. Serum and CSF procalcitonin levels are of no value for differentiation between early localised, early disseminated and chronic Lyme borreliosis.     

Assessment of Association between Common Variants at 17q12 and Prostate Cancer Risk—Evidence from Serbian Population and Meta‐Analysis

This study aimed to evaluate possible association between genotypes and alleles of two 17q12 polymorphisms (rs3760511 and rs7501939) and prostate cancer (PCa) risk and progression. Two hundred seventy‐one patients with PCa, 261 patients with benign prostatic hyperplasia (BPH), and 171 controls were included in the study. Single nucleotide polymorphisms (SNPs) were genotyped by using PCR followed by restriction fragment length (PCR‐RFLP) analysis. We conducted meta‐analysis of published studies regarding association of these SNPs with PCa risk. Evidence of positive association between the AC genotype of the SNP rs3760511 and BPH risk for the best‐fitting overdominant model of association (BPH vs. controls comparison, p = 0.026; odds ratio [OR] = 1.58; 95% confidence interval [95%CI] 1.05–2.36) were obtained. The association between T allele of rs7501939 and PCa risk was determined in PCa versus controls comparison (p = 0.0032; OR = 0.66, 95%CI 0.50–0.87) with the best‐fitting model of inheritance being log‐additive. This variant was also found to be associated with the risk of BPH (p = 0.0023; OR = 0.65, 95%CI 0.49–0.86). We found no association between parameters of PCa progression and the analyzed SNPs. Meta‐analysis showed strong association between these variants and PCa risk. Our study shows association between SNPs at locus 17q12 and the risk of prostatic diseases in Serbian population. At the same time, results of meta‐analysis suggest the association of these SNPs with PCa risk.     

Mistletoe Lectin I-Induced Effects on Human Cytotoxic Lymphocytes. I. Synergism with Il-2 in the Induction of Enhanced Lak Cytotoxicity

This report demonstrates that in vitro activation of human cells with the β-galactoside-specific lectin from mistletoe (ML-I) or interleukin-2 (IL-2) results in different patterns of activation and function of cytotoxic cells. It is now well established that natural killer (NK) and lymphokine-activated killer (LAK) cytotoxicity is mainly mediated by resting (NK) and IL-2-activated (LAK) CD56-positive (+) cells respectively. Culture of peripheral blood lymphocytes (PBL) for 3 days with ML-I led to expansion and activation of T cells which demonstrated NK-and LAK-like cytotoxicity. T lymphocyte subset analysis revealed that in total PBL, ML-I preferentially stimulated and expanded CD8+ T cells which mediated the cytotoxic effect. Incubation of highly purified CD8+ T cells alone with ML-I did not lead to induction of cytotoxicity, which required the presence of both CD4+ and CD 14+ (monocytes) cells, suggesting that ML-I does not exert a direct effect on CD8+ T cells. Activation of PBL with both ML-I and IL-2 resulted in simultaneous induction of T and CD56+ cell-mediated NK and LAK cytotoxicity. These data suggest that treatment with ML-I and DL-2 might provide an approach to induce maximum cytotoxicity against tumors and to recruit both T and NK cells for tumor therapy.     

Solitary borrelial lymphocytoma in adult patients

During the period from 1986 to 2000, 85 adult patients with solitary borrelial lymphocytoma were diagnosed at the Department of Infectious Diseases, University Medical Centre Ljubljana, Slovenia. There were 36 (42.4%) females and 49 (57.6%) males with a median age of 49 (15-74) years. Borrelial lymphocytoma was located on the breast (nipple--areola mammae region) in 68 (80%) patients, on the ear lobe in eight (9.4%), and in other locations in nine (10.6%). A concomitant erythema migrans enabling clinical diagnosis of Lyme borreliosis was registered or reported in 67 (78.8%) patients. Fifteen (17.6%) patients had no accompanying symptoms, 34 (40%) reported local and constitutional symptoms, 23 (27.1%) recounted only local symptoms, and 13 (15.3%) patients had solely constitutional symptoms. Clinical findings indicating early disseminated borrelial infection were observed at the first visit in 12 (14.1%) patients: six (7.1%) had multiple erythema migrans, one had meningitis, one meningoradiculitis and arthritis, one radiculoneuritis and arthritis, one peripheral facial palsy and concomitant meningitis, and two arthritis. In addition, one of the patients with borrelial lymphocytoma on the breast had acrodermatitis chronica atrophicans. A seropositive response to borrelial antigens was found in 30 (35.3%) patients at the initial examination. In 11/46 (23.9%) patients, infection with Borrelia burgdorferi sensu lato was confirmed by isolation of the agent from lymphocytoma tissue. Eight out of nine (88.9%) typed borrelial strains were found to be B. afzelii, and one (11.1%) B. bissettii. Patients were treated with doxycycline, azithromycin, amoxycillin, cefuroxime-axetil, phenoxymethylpenicillin, or ceftriaxone. Median time to complete disappearance of lymphocytoma was 28 days (range 7-270 days) after the institution of antibiotic treatment; disappearance took longer in patients with prolonged duration of the skin lesion prior to treatment. Treatment failure was registered in 11 (12.9%) patients who were later re-treated. The outcome of borrelial infection assessed at the end of a follow-up period of one year was favourable.     

Hand-foot-mouth disease

A case of hand-foot-and-mouth disease is reported in a 20-year-old female patient. Infection by Coxsackie A 16-virus was diagnosed by serology.     

Epidemiology of myotonic dystrophy type 1 (Steinert disease) in Belgrade (Serbia)

The aim of this study was to estimate the incidence and prevalence of myotonic dystrophy type 1 (DM1) in Belgrade during the period 1983–2002.

The patients who had DM1 were ascertained through hospital records from all neurological departments in Belgrade during 1983–2002. The molecular genetic analysis was performed in all patents included in the study.

We identified 101 DM1 patients (52 males and 49 females). The average annual incidence rate of DM1 in Belgrade for the period observed was 2.0/1,000,000 (95% confidence interval (CI), 0.3–8.3), 2.1/1,000,000 (95% CI, 0.3–8.3) for males and 2.0/1,000,000 (95% CI, 0.3–8.3) for females. The highest age-specific DM1 incidence was registered in the age group 20–49: 3.4/1,000,000 (95% CI, 0.5–7.6), 4.0/1,000,000 (95% CI, 1.1–10.2) in males and 2.5/1,000,000 (95% CI, 0.5–7.6) in females. In the population of Belgrade, a cumulative probability of acquiring DM1 was 1 per 8621 for men and 1 per 9259 for women (1 per 8940 of the population for both sexes). The prevalence of DM1 in Belgrade on 31 December 2002 was 5.3/100,000 (95% CI, 4.2–6.6).     

Doxycycline versus ceftriaxone for the treatment of patients with chronic Lyme borreliosis

BACKGROUND: Therapeutic guidelines for treatment of late manifestations of Lyme borreliosis have not yet become well established. Patients with symptoms suggesting central nervous system involvement are often treated with courses of intravenous ceftriaxone. This is an expensive treatment approach with potentially severe side effects. We compared the efficacy, side effects and costs of doxycycline and ceftriaxone in the treatment of such patients. PATIENTS AND METHODS: Adult patients qualified for the study if they had nonspecific symptoms suggesting central nervous system involvement for more than six months (but without overt clinical signs of the involvement), had positive serum borrelial antibody titers and/or erythema migrans prior to the onset of symptoms, had not been previously treated with antibiotics and did not have pleocytosis in the cerebrospinal fluid. Patients were given either 100 mg of oral doxycycline twice daily for 4 weeks (23 patients) or 2 g of intravenous ceftriaxone daily for 2 weeks followed by 100 mg of doxycycline twice daily for another 2 weeks (23 patients). Clinical outcome was assessed during a 12-month follow-up period. RESULTS: Improvement in the frequency and/or the intensity of symptoms was reported by more than two-thirds of the 46 patients enrolled in the study. The two treatment regimens were found to be correspondingly effective. Photosensitivity reactions and gastrointestinal symptoms were noted more often among patients receiving doxycycline than in those receiving ceftriaxone. Treatment with doxycycline proved to be much cheaper than with ceftriaxone. CONCLUSIONS: In patients with previously untreated chronic Lyme borreliosis with symptoms suggesting central nervous system involvement but without overt clinical signs of it, and without pleocytosis in the cerebrospinal fluid, treatment with doxycycline is as effective as with ceftriaxone. Treatment with doxycycline is cheap and relatively safe, but gastrointestinal symptoms and photosensitivity reactions can be expected more often than with ceftriaxone.