Baclofen - a great chance or danger - discussion of poisoning based on research

Introduction and purpose: Baclofen is a derivative of γ-aminobutyric acid (GABA). It is a spasmolytic drug that reduces skeletal muscle tension and is used in spasticity. Despite its many positive functions, its use is associated with a risk of side effects. The aim of this work is to gain a better understanding of baclofen and to highlight the toxicity and dangers of its misuse. Material and methods: The study was retrospective in nature. It used an analysis of the records of 11648 intoxications in patients hospitalised from 01.04.2013 to 01.04.2023 in the Clinical Toxicology and Cardiology Department of the Stefan Cardinal Wyszyński Provincial Hospital in Lublin, from which a group of baclofen intoxicated patients (T55), consisting of 19 cases, was distinguished. Results: The study population consisted of 10 women (52.63%) and 9 men (47.37%), aged between 16 and 83 years. The largest group consisted of patients aged up to 30 years - 9 patients (47.37%). The majority of patients - 11 patients (59.89%) were in a severe condition. An overwhelming number reported intentional poisoning - 16 cases (84.21%), including five suicide attempts (31.25%). Patients took other drugs and medicines in addition to baclofen. The most common was ethanol - 8 people (42.11%), followed by NSAIDs - 5 people (26.32%). Conclusions: In order to prevent complications following the use of baclofen, it is very important to educate patients, their family members and the general public about the mechanism of action of the drug itself, its function on the body and the risks of taking it. Prophylactic measures and education on how to deal with poisoning situations are necessary, as they are entirely preventable with immediate diagnosis and treatment

ICOS gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

There is strong evidence that altered immunological function entails an increased risk of B-cell chronic lymphocytic leukemia (B-CLL). The main mechanism of an anti-tumor response depends on T-cell activation. Unlike the constitutively expressed CD28, inducible costimulatory molecule (ICOS) is expressed on the T-cell surface after activation. ICOS enhances all the basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, the upregulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B cells. ICOS is essential for both efficient interaction between T and B cells and normal antibody responses to T cell-dependent antigens. It does not upregulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Our previous results indicated the ICOS gene has a role as a susceptibility locus to B-CLL. Therefore an extended study was undertaken to evaluate the association between four ICOS polymorphisms (which were recently described as functional ones) and susceptibility to B-CLL in the Polish population. A case-control study of 296 individuals, including 146 B-CLL patients, was conducted on four polymorphisms in the ICOS gene. Genotyping of the polymorphisms ICOS ISV1+173T>C (rs10932029), ICOSc.1624C>T (rs10932037), ICOSc.2373G>C (rs4675379), and ICOSc.602A>C (rs10183087) was carried out using allelic discrimination methods with the TaqMan® SNP Genotyping Assay. There were no statistically significant differences in the allele, genotype, or haplotype distributions between B-CLL patients and healthy controls for any of the investigated polymorphic markers in the ICOS gene. However, we noted that patients carrying genotype ICOS ISV1+173T>C [TT], ICOSc.602A>C [AA], ICOSc.1624C>T [CC], and ICOSc.2373G>C [GG] have a decreased frequency of progression to a higher Rai stage during 60-month follow-up (21.35% vs. 40.8%, p = 0.013) compared to other individuals. This indicates that the investigated polymorphisms do not modulate the risk of B-CLL in the Polish population, but are associated with disease dynamics, in particular with the time to Rai stage progression. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 49–54

Genetic variants in transforming growth factor-β gene (TGFB1) affect susceptibility to schizophrenia

Immense body of evidence indicates that dysfunction of immune system is implicated in the etiology of schizophrenia. The immune theory of schizophrenia is supported by alterations in cytokine profile in the brain and peripheral blood. Given the strong genetic background of schizophrenia, it might be assumed that aberrant production of cytokines might be the consequence of genetic factors. This study aimed at investigating the association between schizophrenia susceptibility and selected functional polymorphisms in genes encoding cytokines including: interleukin-2 (IL2 −330T>G, rs2069756), interleukin-6 (IL-6 −174G>C, rs1800795), interferon-γ (IFNG +874T>A, rs2430561) as well as for the first time transforming growth factor-β1 (TGFB1 +869T>C, rs1800470 and +916G>C, rs1800471). We recruited 151 subjects with schizophrenia and 279 controls. There was a significant difference in the genotype distribution and allelic frequency of the TGFB1 +869T>C between patients with schizophrenia and healthy controls (p < 0.05). The risk of schizophrenia was more than two-fold higher in carriers of T allele (CT+TT genotypes) than individuals with CC genotype. Given documented gender differences in incidence of schizophrenia, we conducted separate analyses of male and female participants. We have shown that the association was significant in females, while in males it reached a trend toward statistical significance. To the best of our knowledge, it is the first report showing the association between TGFB1 +869T>C polymorphism and schizophrenia

Baclofen - a great chance or danger - discussion of poisoning based on research

Introduction and purpose: Baclofen is a derivative of γ-aminobutyric acid (GABA). It is a spasmolytic drug that reduces skeletal muscle tension and is used in spasticity. Despite its many positive functions, its use is associated with a risk of side effects. The aim of this work is to gain a better understanding of baclofen and to highlight the toxicity and dangers of its misuse. Material and methods: The study was retrospective in nature. It used an analysis of the records of 11648 intoxications in patients hospitalised from 01.04.2013 to 01.04.2023 in the Clinical Toxicology and Cardiology Department of the Stefan Cardinal Wyszyński Provincial Hospital in Lublin, from which a group of baclofen intoxicated patients (T55), consisting of 19 cases, was distinguished. Results: The study population consisted of 10 women (52.63%) and 9 men (47.37%), aged between 16 and 83 years. The largest group consisted of patients aged up to 30 years - 9 patients (47.37%). The majority of patients - 11 patients (59.89%) were in a severe condition. An overwhelming number reported intentional poisoning - 16 cases (84.21%), including five suicide attempts (31.25%). Patients took other drugs and medicines in addition to baclofen. The most common was ethanol - 8 people (42.11%), followed by NSAIDs - 5 people (26.32%). Conclusions: In order to prevent complications following the use of baclofen, it is very important to educate patients, their family members and the general public about the mechanism of action of the drug itself, its function on the body and the risks of taking it. Prophylactic measures and education on how to deal with poisoning situations are necessary, as they are entirely preventable with immediate diagnosis and treatment

Transcranial doppler ultrasonography should it be the first choice for persistent foramen ovale screening?

BACKGROUND: Persistent foramen ovale (PFO) is considered a cause of cryptogenic stroke and a risk factor for neurological events in young patients. The reference standard for identifying a PFO is contrast-enhanced transesophageal echocardiography (TEE). The goal of this study was to evaluate the feasibility of transcranial color Doppler (TCD) and its diagnostic sensitivity compared with TEE. METHODS: We investigated 420 patients admitted to our department with cryptogenic stroke, transient ischemic attacks or other neurological symptoms. All patients underwent TCD and TEE evaluation. TCD and TEE examinations were performed according to a standardized procedure: air-mixed saline was injected into the right antecubital vein three times, while the Doppler signal was recorded during the Valsalva maneuver. During TCD the passage of contrast into the right-middle cerebral artery was recorded 25 seconds following the Valsalva maneuver. RESULTS: We detected a right-to-left shunt in 220 patients (52.3%) and no-shunts in 159 patients (37.9%) with both TCD and TEE. In 20 (4.8%) patients TEE did not reveal contrast passage which was then detected by TCD. In 21 (5.0%) patients only TEE revealed a PFO. The feasibility of both methods was 100%. TCD had a sensitivity of 95% and a specificity of 92% in the diagnosis of PFO. CONCLUSIONS: TCD has a relatively good sensitivity and specificity. TCD and TEE are complementary diagnostic tests for PFO, but TCD should be recommended as the first choice for screening because of its simplicity, non-invasive character, low cost and high feasibility

The scintigraphic diagnosis of cardiac amyloidosis. An expert opinion endorsed by the Section of Nuclear Medicine of the Polish Cardiac Society and the Polish Nuclear Medicine Society

Amyloid transthyretin cardiomyopathy is a progressive disease that confers significant mortality. While it is relatively rare, the frequency of diagnoses has risen with the increased contribution of novel diagnostic approach over the last decade. Traditionally tissue biopsy was considered to be a gold standard for amyloidosis diagnosis. However, there are significant limitations in the wide application of this approach. A noninvasive imaging-based diagnostic algorithm has been substantially developed in recent years. Establishing radionuclide imaging standards may translate into a further enhancement of disease detection and improving prognosis in the group of patients. Therefore we present in the following document current evidence on the scintigraphic diagnosis of cardiac transthyretin amyloidosis. Moreover, we present standardized protocol for the acquisition and interpretation criteria in the scintigraphic evaluation of cardiac amyloidosis

Variations in Suppressor Molecule CTLA-4 Gene Are Related to Susceptibility to Multiple Myeloma in a Polish Population

Various phenotype and functional T-cell abnormalities are observed in multiple myeloma (MM) patients. The aim of this study was to investigate the association between polymorphisms in the gene encoding cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of the T-lymphocyte immune response and susceptibility to multiple myeloma in a Polish population. Two hundred MM patients and 380 healthy subjects were genotyped for the following polymorphisms: CTLA-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CT60 (CTLA-4g.*6230G>A), Jo31 (CTLA-4g.*10223G>T). Our study is the largest and most comprehensive evaluation to date of the association between genetic polymorphisms in the CTLA-4 molecule and multiple myeloma. It was found that CTLA-4c.49A>G[G], CT60[G], and Jo31[G] alleles were more frequently observed in MM patients than in controls (0.50 vs. 0.44, p = 0.03, 0.65 vs. 0.58, p = 0.04, and 0.63 vs. 0.57, p = 0.03, respectively). Moreover, the haplotype CTLA-4c.49A>G[G], CTLA-4g.319C>T[C], CTLA-4g.*642AT(8_33) [8], CT60[G], Jo31[G] including all susceptibility alleles increases the risk of MM about fourfold (OR: 3.79, 95%CI: 2.08–6.89, p = 0.00001). These findings indicate that genetic variations in the CTLA-4 gene play role in susceptibility to multiple myeloma and warrant further investigation through replication studies