In silico evaluation of 4-thiazolidinone-based inhibitors against the receptor for advanced glycation end products (RAGE).

Non-enzymatic glycation of biomolecules by reducing sugars led to several products, including the advanced glycation end products (AGEs), the accumulation of which has been linked to various life-threatening diseases. The binding of AGEs to their respective protein receptors for advanced glycation end products (RAGE) can initiate a cascade of reactions, which may alter physiological conditions. The present work investigates the potential of 4-thiazolidinones as RAGE inhibitors. We performed an extensive computational study to identify the structural requirements needed to act as RAGE inhibitors. To achieve this goal, 4-thiazolidinone-based compounds available in PubChem, ZINC15, ChEMBL, and ChEBI databases were screened against RAGE (PDB: 4LP5), leading to the identification of top five drug-like candidates with a high binding affinity to RAGE V-domain catalytic region. Drug likeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the top-scoring compounds have been studied and discussed. Global molecular descriptors, chemical reactivity, hardness, softness, etc., have been estimated. Finally, molecular dynamics (MD) simulations at 100 ns were carried out to check the stability and other properties. Overall, we believe that the identified compounds can potentially attenuate RAGE-AGE interactions.Communicated by Ramaswamy H. Sarma.

A Study to Analyze Refractive Errors in Relation to Age and Sex.

Background and objective Refractive defects should be detected and treated early to avoid irreversible vision loss and other potential problems in the future. In this study, we aimed to analyze the refractive errors (REs) and their relationship with gender and age. Methods This study was conducted at the Northern Border University Health Center, Arar, Saudi Arabia. REs were analyzed using spherical equivalents (SEs), cylinders, and their orientations. SEs of REs were taken as half the cylinder plus the spherical component. Emmetropia was defined as SE between -0.50 and +0.50 diopter sphere (DS), myopia as SE ≤0.50 DS, and hyperopia as SE ≥0.50 DS for adults and SE ≥1.0 for children (up to 10 years). Statistical analysis was performed using the IBM SPSS Statistics software package (IBM, Armonk, NY). Qualitative data were presented as frequency and percentage while quantitative data were presented as mean and standard deviation (SD). Chi-square was used as a significant test and a p-value <0.05 was considered statistically significant. Results A total of 240 patients were included in the study. There were 138 men and 102 females aged 3-60 years (57.5 and 42.5%, respectively). The mean age of males was 24.4 years and that of females was 25.5 years. The p-value was statistically significant in terms of analysis with age. The study found an association between age and RE magnitude and variability. Conclusion Based on our findings, RE is a common problem that affects individuals of all ages. Regular screenings are advised for individuals in order to detect REs early.

Is procalcitonin a reliable indicator of sepsis in spinal cord injury patients: an observational cohort study.

STUDY DESIGN: Prospective observational cohort study. OBJECTIVE: To understand if serum procalcitonin (PCT) is a reliable indicator of sepsis in spinal cord injury (SCI) patients for better prognosis and earlier diagnosis when compared with other common biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), blood culture and body temperature. METHODS: From March 2021 to August 2022, data were collected for SCI patients who developed septicaemia. In addition to neurology and admission, the following blood samples were collected on day one of infection: PCT, CRP and WBC. Linear regression analysis was performed to determine the relationship between PCT, CRP and WBC. RESULTS: A total of 27 SCI patients had an infection during their stay in the regional centre; however, only 10 developed septicaemias. 100% of SCI individuals with sepsis had elevated PCT levels, whilst 60% had elevated CRP and 30% had elevated WBC levels. There was a strong positive correlation between PCT and CRP (R2 = 0.673, CI = 95%, 5.5-22.8, p < 0.05) and a weaker positive correlation between PCT and WBC (R2 = 0.110, CI = 95%, 4.2-10.9, p < 0.05). CONCLUSION: In SCI individuals, there was a correlation between serum PCT levels and septicaemia. Alongside this, PCT appeared to be more consistent throughout the study population when compared with CRP and WBC. However, this was a preliminary study and further research is required on a larger scale.

NADP/H binding nearly doubles the stability of a Mycobacterium drug target: an unfolding study.

Mycobacterium Aspartate beta semialdehyde dehydrogenase (ASADH) was studied using various spectroscopic techniques and size exclusion chromatography to examine the unfolding of free (apo) and NADP/H-bound (holo) forms of ASADH. Non-cooperative guanidinium chloride (GdnHCl)-induced unfolding of the apo ASADH was discovered, and no partially folded intermediate structures were stabilized. On the other hand, it was observed that GdnHCl's unfolding of holoenzyme was a cooperative process without any stable intermediate structure. The native form of holoenzyme is found to be stable against the lower concentration of GdnHCl only (namely up to 1.25 M GdnHCl). The tryptophan environment appears to unfold cooperatively in case of the holoenzyme and is in well coordination with the overall unfolding of the holoenzyme. The presence of NADP/H shows a stabilizing effect on the tryptophan environment as well as on the native NADP/H-bound enzyme. ΔGSolvento values reveal nearly two-fold (∼1.9) conformationally more stable folded holoenzyme compared to its native apo state. The Cm for the apo and holo forms of ASADH are 1.3 and 1.9 M, respectively. Novel drug leads targeting the NADP/H binding domain of ASADH could offer promising drugs against extremely infective Mycobacterium tuberculosis.Communicated by Ramaswamy H. Sarma.

Long-Term Clinical Outcome of Tacrolimus Skin Ointment (0.03%) for the Treatment of Vernal Keratoconjunctivitis: A Quasi-Experimental Study.

Background Vernal keratoconjunctivitis (VKC) is an allergic conjunctival inflammation with severe ocular complications if left untreated. The current management regimen is plagued with adverse effects, long-term problems, and clinical relapses. Tacrolimus offers an alternative treatment option, and long-term studies are needed to determine its efficacy. Methods A two-year follow-up based study was conducted on moderate to severe VKC patients, who were prescribed tacrolimus skin ointment. The 5-5-5 exacerbation scale was used for the monitoring and grading severity of the disease. Analysis of variance (ANOVA) and intergroup comparisons were conducted on exacerbation scale scores among follow-ups. Results A significant reduction was observed in the total score of severity from baseline (203.17±102.05) to three months' follow-up (69.94±70.54), and it kept reducing for 18 months post therapy. Similar results with statistically significant reduction were observed for all grades of the scale. The relapse rate was 5.71% within a month after therapy cessation, and none of the other patients showed relapse afterward. No significant ocular and systemic complications were observed during the study. Conclusion Tacrolimus is effective in the long-term management of VKC without the complications of conventional steroid-based therapy.

Nuclear model analysis and optimization of production data of the medically interesting 66,67,68 Ga via alpha induced reactions on 63,65 Cu targets.

Evaluation of the 63Cu(α,n)66Ga, 65Cu(α,2n) 67Ga and 65Cu(α,n)68Ga reactions was done to study the production of medical radionuclides 66Ga, 67Ga and 68Ga respectively. 63Cu(α,2n)65Ga and 65Cu(α,3n)66Ga reactions were also evaluated for the estimation of radioisotopic impurities. Cross section data of each reaction were compiled and normalized to the standard values of decay data and monitor reaction. To check the consistency of the literature data, three nuclear model calculations were performed, using nuclear model codes; TAYLS 1.9, ALICE-IPPE, and EMPIRE 3.2. A well-developed evaluation methodology based on the normalized experimental data and nuclear model calculations was used to generate the statistically fitted cross sections. From the fitted cross sections, thick target yields for each reaction were calculated for the estimation of radioisotopic impurities. Finally, a suitable energy region for the production of 66Ga, 67Ga and 68Ga was suggested with a minimum level of radioisotopic impurities.

Peripheral Neuropathy in Beta-Thalassemia: Corneal Confocal Microscopy-Based Study.

Background Peripheral neuropathy is a controversial but serious complication of beta-thalassemia (ß-Th). Although few studies have reported no relationship between neuropathy and thalassemia, many have linked it with increasing age, iron overload, and iron chelator toxicity. This study aims to investigate the presence of neuropathy in ß-Th using corneal nerve fibers. Methodology A cross-sectional study was conducted using corneal confocal microscopy on individuals with intermediate and major ß-Th who were compared to healthy individuals. The main outcome variables were corneal main nerve and branch nerve densities which were calculated using Image J software. The comparison between groups was done using the independent-samples F-test and Bonferroni post-hoc analysis. Results There was reduced corneal main nerve and branch nerve density in ß-Th intermediate and major patients compared to the control group, and the results were statistically significant (p-value <0.05). However, a significant correlation was not observed between serum ferritin levels and corneal nerve parameters. Conclusions The reduction in corneal nerve parameters in ß-Th patients compared to healthy controls can be an indication of peripheral neuropathy in ß-Th. Further work is needed to confirm these findings.

The psychological impact of COVID-19 on healthcare workers in Pakistan.

INTRODUCTION: The COVID-19 pandemic has challenged healthcare facilities and healthcare professionals' stamina and wellbeing. This study examines the psychological impact of COVID-19 on healthcare professionals. METHODS: This analytical cross-sectional study was conducted in July 2020 after institutional review board approval at a tertiary care institution in Lahore, Pakistan. A total of 175 healthcare workers participated following an online Depression, Anxiety and Stress Scale-21 (DASS-21) questionnaire invitation and 41 were excluded following pre-existing mental health conditions. Data was analysed using MS Excel and SPSS Amos 23. Chi-squared test and regression were applied for comparison and impact of confounding variables respectively (p<0.05 was considered significant). RESULTS: Out of 134, 66 (49%) were doctors, 24 (18%) were nurses and 44 (33%) were non-medical professionals. Ninety-five (70%) with age 21-30 years. Male to female ratio was 2:1. Overall mean depression score accounted for 6.89 ± 6.64; anxiety score was 7.28 ± 6.74 and stress score was 8.83 ± 6.93. Mild depression, anxiety and stress was noted in 21 (15.6%), eight (6%) and 27 (20.1%) healthcare workers, respectively. A statistically significant difference (p<0.05) was observed among healthcare workers for depression, anxiety and stress. CONCLUSION: This study demonstrated considerable impact of COVID-19 on mental health of healthcare workers. A well-structured targeted mental health support programme is needed urgently to support and reduce the long-term impact on healthcare workers' mental health and wellbeing.

Prescription understanding among out-patients in government and private hospitals: A cross-sectional study in Lahore, Pakistan.

INTRODUCTION: Like many other countries, Pakistan's healthcare system is divided into the public and the private sector. According to some studies and the mindset of many Pakistani people, private hospitals provide better services than government hospitals. PURPOSE: The paucity of research studies compelled us to compare the understanding of prescription among outpatients of the government and private hospitals since the understanding of prescription by the patient is an important patient care indicator according to WHO. METHOD: A cross sectional study was conducted by virtue of convenience sampling. The study included 365 patients; 182 from the government sector and 183 from the private sector. The study was conducted over a period of 3 months. A structured questionnaire was prepared to gather data that was analyzed using SPSS Version 22.0. RESULTS: Patients from both government and private hospitals got no counseling while only 45.9% of the government hospital patients and 65.9% of private hospital patients were satisfied with the counseling they received. Our study concluded that the role of a pharmacist must be extended besides dispensing only, in counseling and educating patients to reduce the burden on the physicians and hospitals as well. CONCLUSION: It was concluded that although the patients of private hospitals scored somewhat better at answering the questions than the government hospital patients but they failed to hit the benchmark. Their slightly better results were attributed to higher education levels and better socioeconomic status rather than better services of the hospital.

Seroprevalence of Toxoplasma gondii and associated hematological alterations in small ruminants of D.G. Khan district of Southern Punjab, Pakistan / [Soroprevalência de Toxoplasma gondii e alterações hematológicas associadas em pequenos ruminantes no distrito de D.G. Khan no sul de Punjab, Paquistão]

The present study was carried out to evaluate the prevalence and hematological effects of Toxoplasma gondii in sheep and goat in district Dera Ghazi Khan. Blood samples (n=204) were collected comprise goats (n=101) and sheep (n=103) alongwith age, gender and breeds of animals. Samples were collected randomly from 25 flocks of 7 different union council Viz. Vehova, Tibbi Qaisrani, Lakhani, Kohar, Tuman Qaisrani, Nutkani and Kot Qaisrani of Tehsil Taunsa Sharif at least 4 animals from each flock. All ruminants divide into three groups based on age, breed and gender. The prevalence was detected through two different kits Viz. LAT and ELISA kit. The overall prevalence suspected in goats through LAT and ELISA kit was (35.64%), (32.67%) and in sheep was (25.24%), (23.30%) respectively. The Toxoplasma gondii had a significant effect on goats in age groups and non-significant all other groups of goats and sheep. Toxoplasma gondii had a significant effect on all hematological parameters like Hemoglobin, total leukocyte cells, granulocytes, lymphocytes, platelets, and red blood cells, except monocytes. In conclusion of the current study, toxoplasmosis is prevalent among ruminants, reveals the possibility of transmission to humans on the use of host animals as protein source.(AU)

O objetivo do presente estudo foi avaliar a prevalência e efeitos hematológicos de Toxoplasma gondii em ovelhas e cabras no distrito Dera Ghazi Khan. Amostras de sangue (n=204) foram coletadas para incluir cabras (n=101) e ovelhas (n=103), além de idade, gênero e raça dos animais. Amostras foram coletadas aleatoriamente de 25 rebanhos de 7 conselhos sindicais: Vehova, Tibbi Qaisrani, Lakhani, Kohar, Tuman Qaisrani, Nutkani e Kot Qaisrani of Tehsil Taunsa Sharif com pelo menos 4 animais em cada rebanho. Todos os ruminantes foram divididos em três grupos baseados em idade, raça e gênero. A prevalência foi detectada usando dois kits, LAT e ELISA. A prevalência total suspeita em cabras através dos kits LAT e ELISA foi (35.64%), (32.67%) e em ovelhas foi (25.24%), (23.30%) respectivamente. O Toxoplasma gondii teve efeito significativo em cabras em grupos de idade e não significativo em todos os outros grupos de cabras e ovelhas. Toxoplasma gondii teve efeito significativo em todos os parâmetros hematológicos como hemoglobina, células totais de leucócitos, granulócitos, linfócitos, plaquetas e glóbulos vermelhos, exceto monócitos. O presente estudo conclui que toxoplasmose é prevalente entre ruminantes, e revela a possibilidade de transmissão para humanos com o uso de animais hospedeiros como fonte de proteína.(AU)

Evaluation of nuclear reaction cross sections for optimization of production of the important non-standard positron emitting radionuclide 89Zr using proton and deuteron induced reactions on 89Y target.

89Zr (T1/2 = 3.27 d) is an important ß+-emitting radionuclide of zirconium used in immuno PET. The excitation functions of the 89Y(d,2n)89Zr and 89Y(p,n)89Zr reactions were analyzed to deduce the optimum conditions for the high purity production of 89Zr. The nuclear model codes ALICE-IPPE, EMPIRE 3.2 and TALYS 1.9 were used to check the consistency and reliability of the experimental data. A polynomial fit to the chosen data for each reaction gave the excitation function, which was then used for the integral yield calculation of the product. The amount of the major radioactive impurity 88Zr was precisely analyzed for both the proton and the deuteron induced reactions on the 89Y target.

Synergistic targeting of breast cancer stem-like cells by human γδ T cells and CD8+ T cells.

The inherent resistance of cancer stem cells (CSCs) to existing therapies has largely hampered the development of effective treatments for advanced malignancy. To help develop novel immunotherapy approaches that efficiently target CSCs, an experimental model allowing reliable distinction of CSCs and non-CSCs was set up to study their interaction with non-MHC-restricted γδ T cells and antigen-specific CD8+ T cells. Stable lines with characteristics of breast CSC-like cells were generated from ras-transformed human mammary epithelial (HMLER) cells as confirmed by their CD44hi CD24lo GD2+ phenotype, their mesenchymal morphology in culture and their capacity to form mammospheres under non-adherent conditions, as well as their potent tumorigenicity, self-renewal and differentiation in xenografted mice. The resistance of CSC-like cells to γδ T cells could be overcome by inhibition of farnesyl pyrophosphate synthase (FPPS) through pretreatment with zoledronate or with FPPS-targeting short hairpin RNA. γδ T cells induced upregulation of MHC class I and CD54/ICAM-1 on CSC-like cells and thereby increased the susceptibility to antigen-specific killing by CD8+ T cells. Alternatively, γδ T-cell responses could be specifically directed against CSC-like cells using the humanised anti-GD2 monoclonal antibody hu14.18K322A. Our findings identify a powerful synergism between MHC-restricted and non-MHC-restricted T cells in the eradication of cancer cells including breast CSCs. Our research suggests that novel immunotherapies may benefit from a two-pronged approach combining γδ T-cell and CD8+ T-cell targeting strategies that triggers effective innate-like and tumour-specific adaptive responses.

Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes.

Peritonitis remains the major obstacle for the maintenance of long-term peritoneal dialysis and dysregulated host peritoneal immune responses may compromise local anti-infectious defense, leading to treatment failure. Whilst, tissue mononuclear phagocytes, comprising macrophages and dendritic cells, are central to a host response to pathogens and the development of adaptive immune responses, they are poorly characterized in the human peritoneum. Combining flow cytometry with global transcriptome analysis, the phenotypic features and lineage identity of the major CD14+ macrophage and CD1c+ dendritic cell subsets in dialysis effluent were defined. Their functional specialization was reflected in cytokine generation, phagocytosis, and antigen processing/presentation. By analyzing acute bacterial peritonitis, stable (infection-free) and new-starter patients receiving peritoneal dialysis, we identified a skewed distribution of macrophage to dendritic cell subsets (increasing ratio) that associated with adverse peritonitis outcomes, history of multiple peritonitis episodes, and early catheter failure, respectively. Intriguingly, we also noted significant alterations of macrophage heterogeneity, indicative of different maturation and activation states that were associated with different peritoneal dialysis outcomes. Thus, our studies delineate peritoneal dendritic cells from macrophages within dialysate, and define cellular characteristics associated with peritoneal dialysis treatment failure. These are the first steps to unravelling the detrimental adaptive immune responses occurring as a consequence of peritonitis.

Potential Use of γδ T Cell-Based Vaccines in Cancer Immunotherapy.

IMMUNOTHERAPY IS A FAST ADVANCING METHODOLOGY INVOLVING ONE OF TWO APPROACHES: (1) compounds targeting immune checkpoints and (2) cellular immunomodulators. The latter approach is still largely experimental and features in vitro generated, live immune effector cells, or antigen-presenting cells. γδ T cells are known for their efficient in vitro tumor killing activities. Consequently, many laboratories worldwide are currently testing the tumor killing function of γδ T cells in clinical trials. Reported benefits are modest; however, these studies have demonstrated that large γδ T-cell infusions were well tolerated. Here, we discuss the potential of using human γδ T cells not as effector cells but as a novel cellular vaccine for treatment of cancer patients. Antigen-presenting γδ T cells do not require to home to tumor tissues but, instead, need to interact with endogenous, tumor-specific αß T cells in secondary lymphoid tissues. Newly mobilized effector αß T cells are then thought to overcome the immune blockade by creating proinflammatory conditions fit for effector T-cell homing to and killing of tumor cells. Immunotherapy may include tumor antigen-loaded γδ T cells alone or in combination with immune checkpoint inhibitors.

Microbe-specific unconventional T cells induce human neutrophil differentiation into antigen cross-presenting cells.

The early immune response to microbes is dominated by the recruitment of neutrophils whose primary function is to clear invading pathogens. However, there is emerging evidence that neutrophils play additional effector and regulatory roles. The present study demonstrates that human neutrophils assume Ag cross-presenting functions and suggests a plausible scenario for the local generation of APC-like neutrophils through the mobilization of unconventional T cells in response to microbial metabolites. Vγ9/Vδ2 T cells and mucosal-associated invariant T cells are abundant in blood, inflamed tissues, and mucosal barriers. In this study, both human cell types responded rapidly to neutrophils after phagocytosis of Gram-positive and Gram-negative bacteria producing the corresponding ligands, and in turn mediated the differentiation of neutrophils into APCs for both CD4(+) and CD8(+) T cells through secretion of GM-CSF, IFN-γ, and TNF-α. In patients with acute sepsis, circulating neutrophils displayed a similar APC-like phenotype and readily processed soluble proteins for cross-presentation of antigenic peptides to CD8(+) T cells, at a time when peripheral Vγ9/Vδ2 T cells were highly activated. Our findings indicate that unconventional T cells represent key controllers of neutrophil-driven innate and adaptive responses to a broad range of pathogens.

Expanded Human Blood-Derived γδT Cells Display Potent Antigen-Presentation Functions.

Cell-based immunotherapy strategies target tumors directly (via cytolytic effector cells) or aim at mobilizing endogenous anti-tumor immunity. The latter approach includes dendritic cells (DC) most frequently in the form of in vitro cultured peripheral blood monocytes-derived DC. Human blood γδT cells are selective for a single class of non-peptide agonists ("phosphoantigens") and develop into potent antigen-presenting cells (APC), termed γδT-APC within 1-3 days of in vitro culture. Availability of large numbers of γδT-APC would be advantageous for use as a novel cellular vaccine. We here report optimal γδT cell expansion (>10(7) cells/ml blood) when peripheral blood mononuclear cells (PBMC) from healthy individuals and melanoma patients were stimulated with zoledronate and then cultured for 14 days in the presence of IL-2 and IL-15, yielding γδT cell cultures of variable purity (77 ± 21 and 56 ± 26%, respectively). They resembled effector memory αßT (TEM) cells and retained full functionality as assessed by in vitro tumor cell killing as well as secretion of pro-inflammatory cytokines (IFNγ, TNFα) and cell proliferation in response to stimulation with phosphoantigens. Importantly, day 14 γδT cells expressed numerous APC-related cell surface markers and, in agreement, displayed potent in vitro APC functions. Day 14 γδT cells from PBMC of patients with cancer were equally effective as their counterparts derived from blood of healthy individuals and triggered potent CD8(+) αßT cell responses following processing and cross-presentation of simple (influenza M1) and complex (tuberculin purified protein derivative) protein antigens. Of note, and in clear contrast to peripheral blood γδT cells, the ability of day 14 γδT cells to trigger antigen-specific αßT cell responses did not depend on re-stimulation. We conclude that day 14 γδT cell cultures provide a convenient source of autologous APC for use in immunotherapy of patients with various cancers.

Functional electrical stimulation for the upper limb in tetraplegic spinal cord injury: a systematic review.

Technological advances have helped to improve functional ability in spinal cord injury survivors. The aim of this study is to systematically review the evidence for functional electrical stimulation (FES) on functional tasks involving the upper limb in people with spinal cord injuries. The authors systematically searched from September 2009 to September 2014 in relevant databases using a combination of keywords covering spinal cord injury and FES. Studies were selected using pre-determined criteria. The search yielded 144 studies. Only five studies met the inclusion criteria. All five reported improvements immediately and at follow-up in functional ability as a result of FES or FES combined with conventional therapy. There is some preliminary evidence that FES may reduce disability due to upper limb-related activity limitations in tetraplegic spinal cord injury. Further work needs to examine the role of FES in more detail and in combination with other treatments.

Broader corneal characterization with PulseESPI applied to elasticity measurements.

PURPOSE: A novel application of pulsed electronic speckle pattern interferometry (PulseESPI) techniques in important corneal elasticity measurements is presented in this pilot study. For laser-ablative procedures like laser-assisted in situ keratomileusis, it has been found that elastic properties of the cornea have a role in the outcome of corneal refractive surgery, while for optimal ablative laser power calculations this measurement method may possibly be helpful. It may also help in earlier diagnosis of degenerative corneal disorders such as keratoconus. METHODS: The approach of this study is to observe dynamic behavior of cornea against stresses as mapped with PulseESPI. For this purpose, strain was induced to the cornea using a fine rod with a mechanical vibrator. RESULTS: It was found that cornea has a response pattern to the dynamic stressing. Its surface exhibits a resonance frequency which can be measured with PulseESPI. This information of resonance frequency can be characteristic to the cornea. CONCLUSIONS: PulseESPI may help in important corneal elasticity measurements used for complication-free optimized ophthalmic surgery. It seems to be a promising method to conduct stress-related investigations on biological samples. To our knowledge, this is the first time that PulseESPI has been used for such ophthalmic measurements.

Experience with oral mexiletine in primary erythromelalgia in children.

Primary erythromelalgia is characterized by burning pain, redness, and warmth in the extremities. We present two cases of primary erythromelalgia both of whom presented with a history of several months of severe burning pain in both hands and feet. Both patients had received multiple pain medications with no improvement in symptoms. Pain was relieved by putting affected parts in ice cold water, which resulted in immersion injury of the affected parts. Both patients stopped taking part in school and social activities. We tried oral mexiletine, a class Ib antiarrythmic agent, in view of its reported role in various chronic painful conditions. Dramatic improvement was observed with its use. Both patients improved after several weeks of use, and there were fewer soaking episodes. We observed no adverse effects with mexilitine therapy.