Cholinergic Syndrome: a Case Report of Acute Organophosphate and Carbamate Poisoning

Cholinergic syndrome is a common topic at western medical universities yet rarely observed in clinical practice. The treatment involves muscarinic antagonists, acetylcholinesterase reactivation, seizure control, and supportive measures. Here we report a case of a 52-year old Caucasian male who attempted suicide by ingesting a purple crystal powder that turned out to be a mixture of carbofuran and chlormephos. At clinical examination, the patient presented with salivation, perspiration, diarrhoea, bradypnoea, loss of consciousness, and epileptic seizures. Laboratory tests showed low plasma cholinesterase, and we started obidoxime along with supportive intensive care treatment. He was later transferred to the psychiatry department for further diagnostics and treatment.     

Heterogeneity in the linear shiny white structures in melanomas seen with polarized light according to histopathological association: Cross-sectional observational study in 118 cutaneous melanomas

Polarized dermoscopy enables visualization of linear shiny white structures in melanomas, thought to be due to the existence of fibrosis in the dermis. Our objective was to establish the existence of two types of linear shiny white structures and assess their association with different histological structures. We performed a cross-sectional study including all non-acral, non-facial melanomas from our hospital with linear shiny white structures. The outcome variable was the type of linear shiny white structures: shiny white streaks and white strands. We evaluated their association with explanatory variables that may affect the reflectance of melanomas and Breslow index. We used χ² statistics and also calculated the sensitivity and specificity of each linear shiny white structure to predict those variables. We detected linear shiny white structures in 118 melanomas. Regarding shiny white streaks, we only found a statistically significant positive relationship with fibrosis in the papillary dermis. Regarding white strands, we found statistically significant and positive relationships with hyperkeratosis, Breslow index of 0.8 mm or more and acanthosis. Sensitivity and specificity study revealed that the presence of shiny white streaks was the most sensitive (81.7%) and specific (72.3%) for fibrosis in the papillary dermis, and presence of white strands was the most sensitive (91.1%) and specific (85.7%) for hyperkeratosis.     

Immunomodulating effects of antibiotics used in the prophylaxis of bacterial infections in advanced cirrhosis

The use of norfloxacin either as primary or secondary prophylaxis of bacterial infections in advanced cirrhosis has improved patient's survival. This may be explained not only due to a significant decrease in the number of infections, but also because of a direct immunomodulatory effect. Selective intestinal decontamination with norfloxacin reduces translocation of either viable bacteria or bacteria-driven products from the intestinal lumen. In addition, norfloxacin directly modulates the systemic inflammatory response. The proinflammatory cytokine profile secreted by neutrophils from these patients shows a close, significant, and inverse correlation with serum norfloxacin levels. Similar effects have been described with other quinolones in different clinical conditions. Although the underlying mechanisms are not well defined for most of the antibiotics, the pathways triggered for norfloxacin to induce such immunomodulatory effects involve the down-regulation of pro-inflammatory inducible nitric oxide synthase, cyclooxygenase-2, and NF-κB and the up-regulation of heme-oxygenase 1 and IL-10 expression. The knowledge of these immunomodulatory effects, additional to their bactericidal role, improves our comprehension of the interaction between antibiotics and the cellular host response and offer new possibilities for the development of new therapeutic strategies to manage and prevent bacterial infections in cirrhosis.     

A systematic review of sugammadex vs neostigmine for reversal of neuromuscular blockade

We reviewed systematically sugammadex vs neostigmine for reversing neuromuscular blockade. We included 17 randomised controlled trials with 1553 participants. Sugammadex reduced all signs of residual postoperative paralysis, relative risk (95% CI) 0.46 (0.29–0.71), p = 0.0004 and minor respiratory events, relative risk (95% CI) 0.51 (0.32–0.80), p = 0.0034. There was no difference in critical respiratory events, relative risk (95% CI) 0.13 (0.02–1.06), p = 0.06. Sugammadex reduced drug‐related side‐effects, relative risk (95% CI) 0.72 (0.54–0.95), p = 0.02. There was no difference in the rate of postoperative nausea or the rate of postoperative vomiting, relative risk (95% CI) 0.94 (0.79–1.13), p = 0.53, and 0.87 (0.65–1.17), p = 0.36 respectively.     

Aging‐related tau astrogliopathy (ARTAG): not only tau phosphorylation in astrocytes

Aging‐related tau astrogliopathy (ARTAG) is defined by the presence of two types of tau‐bearing astrocytes: thorn‐shaped astrocytes (TSAs) and granular/fuzzy astrocytes in the brain of old‐aged individuals. The present study is focused on TSAs in rare forms of ARTAG with no neuronal tau pathology or restricted to entorhinal and transentorhinal cortices, to avoid bias from associated tauopathies. TSAs show 4Rtau phosphorylation at several specific sites and abnormal tau conformation, but they lack ubiquitin and they are not immunostained with tau‐C3 antibodies which recognize truncated tau at Asp421. Astrocytes in ARTAG have atrophic processes, reduced glial fibrillary acidic protein (GFAP) and increased superoxide dismutase 2 (SOD2) immunoreactivity. Gel electrophoresis and western blotting of sarkosyl‐insoluble fractions reveal a pattern of phospho‐tau in ARTAG characterized by two bands of 68 and 64 kDa, and several middle bands between 35 and 50 kDa which differ from what is seen in AD. Phosphoproteomics of dissected vulnerable regions identifies an increase of phosphorylation marks in a large number of proteins in ARTAG compared with controls. GFAP, aquaporin 4, several serine‐threonine kinases, microtubule associated proteins and other neuronal proteins are among the differentially phosphorylated proteins in ARTAG thus suggesting a hyper‐phosphorylation background that affects several molecules, including many kinases and proteins from several cell compartments and various cell types. Finally, present results show for the first time that tau seeding is produced in neurons of the hippocampal complex, astrocytes, oligodendroglia and along fibers of the corpus callosum, fimbria and fornix following inoculation into the hippocampus of wild type mice of sarkosyl‐insoluble fractions enriched in hyper‐phosphorylated tau from selected ARTAG cases. These findings show astrocytes as crucial players of tau seeding in tauopathies.     

Hemorrhagic fever with renal syndrome in the Pomurje region of Slovenia – An 18-year survey

OBJECTIVE: To determine the etiology of hemorrhagic fever with renal syndrome (HFRS) in the north-eastern part of Slovenia (Pomurje region) together with demographic, epidemiological and clinical data on 25 patients from this region who were diagnosed and treated at the General Hospital in Murska Sobota between 1986 and 2003. METHODS: Medical records of patients with a discharge diagnosis of HFRS who were either hospitalized or referred to an infectiologist as outpatients were included in this retrospective study. Data on demographic characteristics, clinical manifestations and laboratory parameters were collected from the patients' records. In addition, all available follow-up records were examined and information on general health, blood pressure, basic blood and biochemical examination and urine analysis was collected. RESULTS: Infection with Puumala virus (PUUV) was indicated in 23 patients and Dobrava virus (DOBV) infection in two patients. The median age of patients was 39 years; 19 were male. The patients primarily had outdoor occupations. Most of the HFRS cases occurred between May and August. The most common findings were fever, vomiting, headache, myalgia, chills, cough, back and abdominal pain, and blurred vision. The most prominent laboratory abnormalities were elevated erythrocyte sedimentation rate and C-reactive protein concentration, thrombocytopenia, and leucocytosis with neutrophilia. The signs of renal dysfunction were observed in 24 of the 25 patients. Oliguric renal failure was seen in 13 of 23 (57%) PUUV-infected patients. Six of 23 (26%) patients infected with PUUV and one of two (50%) patients from the DOBV group had hypotension or developed signs of shock. Seven out of 15 (47%) patients had elevated protein concentration in cerebrospinal fluid (CSF). Sinus bradycardia was documented in 7 of 17 (41%) patients with PUUV infection. CONCLUSIONS: HFRS is endemic in the north-eastern part of Slovenia; PUUV and DOBV infections coexist, with PUUV being the main causative agent of HFRS. Demographic, clinical and laboratory findings in our patients with HFRS caused by PUUV were mostly in accordance with those published previously, but the ratio of patients with sinus bradycardia, oliguric renal failure and mildly elevated CSF protein concentration was rather high.     

Combined search for anti-beta2-glycoprotein I and anticardiolipin antibodies in antiphospholipid syndrome: contribution to diagnosis

In this study we sought to assess (1) the diagnostic value of a combined search for anti-beta(2)-glycoprotein (abeta(2)-GPIs) and anticardiolipin antibodies (aCLs) in primary (APS I) and secondary (APS II) antiphospholipid syndrome and (2) the influence of the beta(2)-GPI preparation in the ELISA's results. abeta(2)-GPI and aCL concentrations were assessed in 70 patients with APS and compared with those in 65 patients with systemic lupus erythematosus (SLE) without clinical features of APS. In APS patients (38 with APS I, 32 with APS II), the diagnosis had to have been made at least 3 years earlier; in subjects with SLE, the diagnosis had to have been made at least 5 years earlier. All serum samples were tested for abeta(2) -GPI with the use of an in-house ELISA with an abeta(2) -GPI preparation from human plasma. Samples negative for abeta(2) -GPI were controlled with 2 additional beta(2)-GPI preparations, 1 from human serum and 1 from bovine serum. In APS, abeta(2)-GPIs were more frequent than in SLE (76% and 15%, respectively; P <.0001), mainly with IgG isotype and with significantly higher levels than those found in SLE. The specificity for APS was 92% for IgG abeta(2)-GPIs and 68% for IgG aCLs. The highest association with APS was found for the combination of the 2 markers (odds ratio 29; 95% confidence interval 10-76; P <.0001). Among the APS patients, 6 were positive for aCL only and remained negative regardless of which beta 2 -GPI preparation was used; 1 patient was aCL-negative and only positive with human beta 2 -GPI. These data emphasize the heterogeneity of the APS immunologic profile and the diagnostic possibilities of both antibodies.     

Cerebrospinal fluid findings in adult patients with multiple erythema migrans

This prospective study was performed at the Department of Infectious Diseases, University Medical Centre Ljubljana, Slovenia, in the period from 1991 to 2000. We included all adult patients with multiple erythema migrans who gave consent to lumbar puncture, had routine blood and CSF tests performed, and borrelial antibody titres in CSF and blood determined. In the majority of these patients skin, blood, and CSF specimens were cultured in MKP medium for the presence of Borrelia. Of 332 patients with multiple erythema migrans, 200 (115 females, 85 males, aged 15-80 years) fulfilled inclusion criteria. The median number of skin lesion was three (2-60). Sixty-three (31.5%) patients had no associated symptoms, whereas 137 (68.5%) patients (including two with arthritis, six with radicular pain, a patient with facial palsy, another patient with foot palsy and a patient with transitory diplopia) reported local and/or constitutional symptoms. Routine CSF examination revealed abnormal results in 62/200 (31%) patients: lymphocytic pleocytosis (6-1119 x 10(6)/L leukocytes) was found in 15 (7.5%) patients (six were clinically without systemic symptoms, six had mild systemic symptoms, three reported radicular pains) and elevated CSF protein concentration was present in 52 (26%) patients (nine also had elevated CSF cell counts). Intrathecal borrelial antibody production was demonstrated in eight (4%) patients (only three of them had elevated CSF cell counts) and B. burgdorferi sensu lato was isolated from skin lesions, blood, and CSF in 77/191 (40.3%), 3/154' (1.95%), and 2/200 (1%) patients, respectively. B. afzelii predominated among the isolates. In patients with multiple erythema migrans abnormal CSF findings are not rare and may be present without any clinical sign of central nervous system involvement.