Postherpetic neuralgia is a common complication, while the postherpetic abdominal-wall pseudohernia (AWP) is a quite rare complication of herpes zoster (HZ). We report a patient >45 years of age with a history of rheumatoid arthritis (RA) who presented with two chronic HZ complications. A 75-year-old woman was admitted with neuralgia following cutaneous herpes zoster 6 weeks before. She was on long-term glucocorticoid, antimalarial and non-steroidal anti-inflammatory treatment. Confluent ulcers began to fill with granulation tissue, crusts, scars and skin discoloration in the area of the left T12-L2 dermatomes and reducible, painless swelling of the left flank, 20 x 20 cm, without palpable defect in abdominal-wall. There were typical joint deformity and positive rheumatoid factor. On neurological examination superficial abdominal reflexes were diminished in the left side, with hypesthesia of the overlying skin. Needle electromyography revealed denervational changes limited to the left-side muscles (on affected dermatomes T12-L2). Thoracoabdominal CT did not reveal the presence of existing hernia. There was an abdominal distension, the left abdominal-wall was thinner than the right side. The patient was treated with an oral preparation containing benfotiamine and vitamins B6 and B12, carbamazepine, amitriptyline, gabapentin, and local lidocaine. Skin rash left with scarring and pigmentary changes and the abdominal-wall swelling resolved within 8 months, however, the pain still persisted. To our best knowledge, this is the first observation of RA-associated postherpetic AWP. This rare motor complication appears to be self-limited with a good prognosis for recovery, while postherpetic neuralgia may require a combination of treatments for adequate pain relief. Older age, female sex, greater rash and acute pain severity are considered as risk factors associated with severe postherpetic neuralgia. In addition, patients with RA, mainly those treated with oral corticosteroids, are also at increased risk of HZ complications.

Abstract Quantitative data on melatonin in stroke patients are scarce. Gender- and age-matched cross-sectional case-control study in 33 patients with ischaemic stroke (IS) was performed and associations between nocturnal melatonin and other factors (e.g., cortisol) evaluated. Clinical and laboratory (e.g., melatonin and cortisol) measurements (3 and 8 a.m.) with statistical techniques [e.g., multifactorial regressions, receiver operating characteristics (ROC) curve and curvilinear estimations] were used. We identified mean value and 95% confidence interval (69.70 pg/ml, 95% CI 53.86-85.54) for control levels of nocturnal melatonin in healthy subjects. The patients with stroke had lower melatonin (48.1+/-35.9 pg/ml) and higher cortisol (297.3+/-157.8 nmol/l) at 3 a.m.(p<0.05) but not at 8 a.m.(p>0.05). The stroke was the strongest factor of disturbed nocturnal cortisol (p<0.001) while decreased melatonin depended on the stroke (p=0.010) and gender (p=0.018). In the same time, vice versa, only nocturnal measures were associated with increased probability of presence of stroke (accuracy>75%, p-model<0.001). Thus, a hypothesis that a decrease of melatonin with 1.0 pg/ml might be associated with >2% increase in the probability of presence of stroke [adjusted odds ratio = 1.020 (95%CI 1.002-1.037)] was also suggested. ROC curve (0.67, p=0.0119) and optimisation techniques indicated that a novel best cut-off<51.5 pg/ml for decreased nocturnal melatonin in the view of the presence of stroke (odds ratio = 3.12, p=0.0463) might exist. The classification performance of such cut-off might be confirmed by existing nocturnal melatonin and cortisol differences between the sub-groups; potential differences in diurnal melatonin were also suggested. In conclusion, a novel melatonin cut-off of 51.5 pg/ml may be associated with the presence of ischaemic stroke. As a single marker (84% sensitivity, 74% specificity), its hypothesised modelling performance was independent of age, gender and cortisol. These new results, including the suggested hypothesis, might be further tested in follow-up (cohort), longitudinal studies and be applied to further explore melatonin disturbances as targets in high-risk pre-stroke and post-stroke patients.

Background/Aims: Risk of ischaemic stroke (IS) was associated with total homocysteine (tHCY). On the other hand, serum selenium (Se) exhibited anti-aging and cardiopreventive effects. Se and tHCY showed relationships in animals but these were contradictory or inconclusive in humans; therefore, we searched for such associations in acute IS. Methods: Ninety-four participants aged around 47 years were identified and 39 patients versus 46 healthy controls were analysed. Clinical, laboratory (blinded) and risk factor questionnaire methods were used. Comparison, correlation and multifactorial regression analyses were applied. Results: IS patients were similar to controls concerning age and gender. IS was prevalent in the carotid system (76.9%); 82.1% had a subacute onset. IS patients expressed higher tHCY (14.65 +/- 9.79 mumol/l) and lower Se levels (1.3 +/- 0.5 mumol/l). Twice as many IS patients (23%) had optimal Se levels of <1.01 mumol/l. Subjects with hyperhomocysteinaemia (tHCY >/=15 mumol/l) showed lower Se levels during IS; Se accounted for 15.4% of tHCY variations (R =-0.393; p = 0.015) with unit change increasing tHCY by 8.25 units. Se remained predictive of tHCY levels after adjustments (vitamin B(6), fibrinogen, triglycerides). Conclusions: Lower Se was observed during acute IS, being inversely associated with and predicting increased tHCY levels. Of note, there were more IS patients with suboptimal Se than controls.

Background: Our previous studies revealed cyclicity in the incidence rate of skin malignant melanoma (SMM; ICD9, Dx:172) in the Czech Republic (period T=7.50~7.63 years), UK (T=11.00 years) and Bulgaria (T=12.20 years). Incidences compared with the sunspot index Rz (lag-period dT=+2,+4,+6,+10 or +12 years) have indicated that maximal rates are most likely to appear on descending slopes of the 11-year solar cycle, i.e., out of phase. We summarized and explored more deeply these cyclic variations and discussed their possible associations with heliogeophysical activity (HGA) components exhibiting similar cyclicity. Methods: Annual incidences of SMM from 5 countries (Czech Republic, UK, Bulgaria, USA and Canada) over various time spans during the years 1964~1992 were analyzed and their correlations with cyclic Rz (sunspot number) and aa (planetary geomagnetic activity) indices were summarized. Periodogram regression analysis with trigonometric approximation and phase-correlation analysis were applied. Results: Previous findings on SMM for the Czech Republic, UK and Bulgaria have been validated, and cyclic patterns have been revealed for USA (T=8.63 years, P<0.05) and Canada (Ontario, T=9.91 years, P<0.10). Also, various 'hypercycles' were established (T=45.5, 42.0, 48.25, 34.5 and 26.5 years, respectively) describing long-term cyclic incidence patterns. The association of SMM for USA and Canada with Rz (dT=+6 and +7 years, respectively) and aa (dT=-10 and +9 years, respectively) was described. Possible interactions of cyclic non-photic influences (UV irradiation, Schumann resonance signal, low-frequency geomagnetic fluctuations) with brain waves absorbance, neuronal calcium dynamics, neuro-endocrine axis modulation, melatonin/serotonin disbalance and skin neuro-immunity impairment as likely causal pathways in melanoma appearance, were also discussed. Conclusion: The above findings on cyclicity and temporal association of SMM with cyclic environmental factors could not only allow for better forecasting models but also lead to a better understanding of melanoma aetiology.

Background: Only few follow-up studies have compared the long-term risk of such major vascular events (MVE) as myocardial infarction (MI) and/or stroke following transient ischaemic attack (TIA) or minor ischaemic stroke (MIS). Estimates of relative risk and cumulative long-term occurrence of MVE may provide better information and contribute to the optimization of treatment decisions. Methods: In the current post hoc modelling study with unique data from Bulgaria, we analysed 183 consecutive patients with TIA (n = 89) or MIS (n = 94), aged >40 years, who were prospectively followed over 36 months for non-fatal or fatal MVE. The cumulative survival, hazard and risks (with 95% confidence intervals) for MVE (combined or by stratification) were calculated by Kaplan-Meier analysis and adjusted (age, sex) by multivariate Cox proportional hazard models. A set of regression models was then applied to MVE incidence (per 100 patients; 4-month intervals). Results: Median follow-up was 36 months (interquartile range 30.8-36.0); no differences by age or sex were found (p > 0.05). The risk of non-fatal or fatal MVE was approximately 28%(stroke 19.7%, MI 8.2%). The adjusted cumulative risk of stroke was 0.21 versus 0.10 for MI. The odds ratio of TIA versus MIS was 0.75 (95% CI 0.43-1.32), i.e. lower for stroke (0.63, 0.31-1.25) than for MI (1.12, 0.40-3.14). The risk of non-fatal MVE was higher in MIS than in TIA (p(Breslow)= 0.0497), especially for non-fatal stroke (p = 0.0325). Time series regression models provided best estimates of the different outcome dynamics in TIA versus MIS (R(2)(TIA)= 0.969 with b(power)= 1.04 vs. R(2)(MIS)= 0.989 with b(linear)= 0.84; p(1-tailed)= 0.04) over the study period. Conclusions: The age- and sex-adjusted cumulative 36-month hazard of MVE is higher after MIS than after TIA, but MVE fatality was higher after TIA than after MIS. Although stroke incidence was higher (up to 3 times that of MI), with the highest difference between months 8 and 18, MI fatality was always higher in absolute, relative or adjusted terms. The above alarming patterns and increasing, diverging tendencies for MVE indicate a higher long-term cumulative risk after MIS compared with TIA. These results confirm our hypothesis of a differential risk of TIA versus MIS and, at least, point toward equal importance of therapies aimed at preventing MVE in both types of preceding conditions (TIA or MIS) and the increased fatality after MI, in particular in patients with TIA. Copyright (c) 2008 S. Karger AG, Basel.

Antiphospholipid syndrome (APS) is primarily considered to be an autoimmune pathological condition that is also referred to as "Hughes syndrome". It is characterized by arterial and/or venous thrombosis and pregnancy pathologies in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disease or secondary to a connective tissue disorder, most frequently systemic lupus erythematosus (SLE). Damage to the nervous system is one of the most prominent clinical constellations of sequelae in APS and includes (i) arterial/ venous thrombotic events,(ii) psychiatric features and (iii) other non- thrombotic neurological syndromes. In this overview we compare the most important vascular ischemic (occlusive) disturbances (VIOD) with neuro-psychiatric symptomatics, together with complete, updated classifications and hypotheses for the etio-pathogenesis of APS with underlying clinical and laboratory criteria for optimal diagnosis and disease management.

This report gives a better emphasis on the role of targeted effectors (e.g. a combination of 5-FC with CD-NSPCs as compared to the application of NSPCs alone) and how such delivery of pro-drug activating enzymes and other tumor-killing substances may overcome melanocytic defence system, interact with and promote the host defence and immune response modulations not only in melanoma but, potentially, in other highly-metastatic cancers.

BACKGROUND & PURPOSE: Hyperhomocysteinaemia has been postulated to participate in pathogenesis of ischaemic stroke (IS). However, especially in young adults, there is possibility of significantly increased IS risk due to increased normal homocysteinaemia, i.e., hidden (pathologically dormant) prevalence within a healthy, normally-defined range. We performed a post-hoc modelling investigation on plasma total homocysteinaemia (THCY) in gender- and age-matched young patients in the acute IS phase. We evaluated relationships between THCY and prevalence of other potential risk factors in 41 patients vs. 41 healthy controls. METHOD: We used clinical methods, instrumental and neuroimmaging procedures, risk factors examination, total plasma homocysteine measurements and other laboratory and statistical modelling techniques. RESULTS: IS patients and healthy controls were similar not only for matching variables, but also for smoking, main vitamin status, serum creatinine and lipid profile. Patients with IS, however, had lower vitamin B6 levels and higher THCY, fibrinogen and triglycerides (TGL). At multivariate stepwise logistic regression only increased THCY and TGL were significantly and independently associated with the risk for stroke (72% model accuracy, p model=0.001). An increase of THCY with 1.0 micromol/L was associated with 22% higher risk of ischaemic stroke [adjusted OR=1.22 (95%CI 1.03?1.44)]. In this way, novel lower cut-off value for HCY of 11.58 micromol/L in younger patients has been revealed (ROC AUC= 0.67, 95CI% 0.55-0.78, p=0.009). CONCLUSION: The new THCY cut-off clearly discriminated between absence and presence of IS (sensitivity>63%, specificity>68%) irrespectively of age and gender and may be applied to better evaluate and more precisely define, as earlier as possible, the young patients at increased IS risk.