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Several attempts have been made to elucidate the pathogenesis of drug-induced gingival overgrowth (DIGO), which is triggered by the chronic use of certain drugs that fall into three main categories: anticonvulsants, immunosuppressants, and calcium channel blockers. Previous research suggests that cytokines and impaired cellular functions play a role in DIGO. Of particular interest are macrophages, immune cells that can switch between M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes in response to exogenous signals and stimuli. An imbalance between M1 and M2 macrophage populations may underlie DIGO. M1 may contribute to the initial tissue damage in DIGO, while M2 may then attempt to repair the damage with anti-inflammatory mechanisms. To test the hypothesis that drugs associated with DIGO could influence macrophage polarization, human monocytes (precursors of macrophages) were induced to differentiate into M0-naïve macrophages and then exposed to drugs: diphenylhydantoin, gabapentin, mycophenolate, and amlodipine. Quantitative real-time PCR amplification was used to measure the expression of specific genes associated with macrophage polarization. All of the drugs tested induced M0 macrophages to overexpress genes typical of the M1 phenotype, such as CCL5, CXCL10, and IDO1. This investigation provides the first evidence of a link between drugs that cause DIGO and M1 pro-inflammatory macrophage polarization. The knowledge gained from this research could be valuable for future DIGO treatment strategies. [ABSTRACT FROM AUTHOR]

Objectives: This study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for the treatment of suspected pneumococcal meningitis. Methods: Data have been prospectively collected for the period1977–2018. From 1987, patients with suspected pneumococcal meningitis received 12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose. They also received (1) a single intravenous dose of 0.5–1 g/Kg mannitol, and (2) antiseizure prophylaxis with phenytoin. Results: In total, 363 episodes of pneumococcal meningitis were recorded. Of these, 242 were treated with the dexamethasone protocol after 1987 and 121 were treated without the protocol. Overall mortality was 11.6% (28/242) among patients treated with dexamethasone and 35% (43/121) among those treated without dexamethasone (p = 0.000). Early mortality was significantly lower at 5.8% (14/242) with dexamethasone and 24% (29/121) without dexamethasone (p = 0.000). Finally, neurological mortality was significantly lower at 7.4% (18/242) with dexamethasone and 23% (28/121) without dexamethasone (p = 0.000). Conclusions: A low dose of dexamethasone along with a single dose of mannitol and antiseizures prophylaxis might be useful for reducing both overall and early mortality in pneumococcal meningitis in adult patients. [ABSTRACT FROM AUTHOR]

Background: Status epilepticus (SE) is defined as 5 min or more of seizure activity or two recurrent seizures without a return to baseline. Healthcare providers encounter a challenge when a patient with SE is pregnant. SE is not only detrimental to the mother but can also put the baby at risk of severe harm. SE must be treated rapidly and therefore healthcare providers have very little time to thoroughly review the risk and benefits of available antiseizure medication in this population. Aim: To evaluate the current available evidence related to the management of SE in pregnancy. Design: A literature search of PubMed, CINAHL, ProQuest Nursing & Allied Health Source, and Web of Science databases was conducted (2012–2022) using the following search terms: 'pregnancy', 'pregnant women' OR 'gestation' AND 'status epilepticus', 'generalized status epilepticus', 'generalized convulsive status epilepticus', 'non convulsive status epilepticus' OR 'non‐convulsive status epilepticus'. Full‐text randomised controlled trials, clinical trials, observational studies, and case reports published in English were included. Data were extracted and the quality of the studies was evaluated using the Mixed Methods Appraisal Tool. Results: The literature described 29 pregnancies and 30 total foetuses. Intravenous benzodiazepine use for emergent control was reported in 45% of patients. Phenytoin and levetiracetam were primarily utilised for urgent control, with a variety of agents used for refractory SE. Ninety‐seven percent of maternal outcomes were reported as positive. The most common outcome was the birth of a healthy term infant. There were seven cases of pregnancy loss. Conclusion: Publications pertaining to the treatment of SE in pregnancy are limited to case reports and small observational studies. Use of a benzodiazepine followed by levetiracetam or phenytoin is appropriate, whereas valproic acid should be utilised only when necessary due to the risk of major congenital malformation. [ABSTRACT FROM AUTHOR]

Acute Generalized Exanthematous Pustulosis (AGEP) is a rare and severe cutaneous adverse reaction characterized by the abrupt onset of widespread sterile pustules on an erythematous base. This is associated with medications, including antiepileptic drugs, phenytoin, and antibiotics such as beta-lactams and macrolides. This is a rare case where a macrolide antibiotic is reported to induce AGEP in an epileptic patient who was on phenytoin therapy. The patient, at the age of 25, was taking phenytoin for the past two years to subside epileptic symptoms. In this period, he has never reported any complications related to AGEP. Including macrolide antibiotics in his prescription aggravated the symptoms of AGEP within a few days. The primary course of action involved immediate withdrawal of both the drugs i.e. phenytoin and macrolide antibiotic, and symptomatic treatment. [ABSTRACT FROM AUTHOR]

Dravet syndrome (DS) is an infantile onset developmental and epileptic encephalopathy. Sodium channel blockers are known to exacerbate seizures in this syndrome. Due to its high incidence, the management of prolonged seizures is crucial for DS patients. There is still ambiguity regarding the use of intravenous phenytoin for prolonged seizure in DS patients mainly due to the lack of data, raising concern about the safety of it use. We conducted a retrospective study (from January 2009 to January 2020) aiming to assess the management of prolonged seizures in DS with a focus on the use of intravenous phenytoin. Data were collected for patients admitted to our hospital for seizures lasting >5 min. Among 52 identified patients in our database, 23 experienced 59 prolonged seizures managed in our hospital. Only four seizures ceased without rescue medication. Notably, the use of intravenous phenytoin was not associated with discernible adverse effects and was effective in stopping status epilepticus in 71% of cases. This study suggests the safety and efficacy of intravenous phenytoin for prolonged seizure in DS. There is a need for broader investigations of emergency treatments for evidence‐based recommendations for the emergency plan of each patient. [ABSTRACT FROM AUTHOR]

Exposure at conception to phenytoin (PHT), phenobarbital (PB), and carbamazepine (CBZ) has been associated with several different effects on the fetus, including hypoplasia of the distal phalanges, dysmorphic facial features, and structural abnormalities such as oral clefts and neural tube defects. One question is whether each of these antiepileptic drugs (AEDs) has the same effects or just similar effects. A systematic examination of the fingers of children exposed at conception to PHT, PB, or CBZ, as monotherapy, has been used to address this question. The findings in the examinations of the fingers of 115 AED‐exposed children (40, PHT; 34, PB; 41, CBZ) and their parents were compared to the findings in 111 age‐ and sex‐matched children and their parents. The evaluations used were both subjective assessments and objective measurements. Shortening and narrowing of the fifth fingernail and an increased frequency of arch patterns in the dermal ridges were more common in PHT‐exposed children. A significant decrease in the length of the nail, but not width, occurred in the PB‐exposed children. Stiffness of the interphalangeal joints was more common in the CBZ‐exposed children. The findings in children exposed to PHT, PB, or CBZ, as monotherapy, showed that all three exposures in early pregnancy affected the fingers, but the effects were not the same. The most striking effects were present in PHT‐exposed children. [ABSTRACT FROM AUTHOR]

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Abstract Background Fosphenytoin (FOS) is a prodrug of phenytoin (PHT) with a metabolism that exhibits Michaelis–Menten-type kinetics. Genetic polymorphisms of the metabolic enzymes of PHT make it challenging to predict its plasma concentrations. High plasma PHT concentrations are typically problematic, and several causes have been elucidated. In contrast, cases of patients with low PHT plasma concentrations that did not increase despite the administration of appropriate PHT doses have been reported, and the causes may include changes in plasma protein-binding rates, genetic mutations, and concomitant use of drugs that induce liver enzymes; however, even these factors do not explain the low PHT plasma concentrations in some cases. Case presentation We encountered the case of a patient with plasma PHT concentrations that were continuously

Abstract We developed a reliable high-performance liquid chromatographic analysis method using a relative molar sensitivity (RMS) technique that does not require an authentic, identical reference analyte material to quantify blood serum carbamazepine, phenytoin, voriconazole, lamotrigine, meropenem, mycophenolic acid, linezolid, vancomycin, and caffeine levels for routine blood concentration measurements. Carbamazepine and caffeine were also used as non-analyte reference materials to calculate the RMS of each analyte. The RMS was calculated from the ratio of the slope of the calibration equation (analyte/non-analyte reference material), then used to quantify analytes in control serum samples spiked with carbamazepine, phenytoin, voriconazole, meropenem, mycophenolic acid, linezolid or vancomycin. In addition, the concentrations of these six drugs in control serum samples determined by the proposed RMS method agreed well with that obtained using a conventional method. The proposed RMS method is a promising tool for the clinical determination of nine drugs, given the accuracy, precision, and efficiency of quantifying these analytes.

Background: Fosphenytoin (FOS) is a prodrug of phenytoin (PHT) with a metabolism that exhibits Michaelis–Menten-type kinetics. Genetic polymorphisms of the metabolic enzymes of PHT make it challenging to predict its plasma concentrations. High plasma PHT concentrations are typically problematic, and several causes have been elucidated. In contrast, cases of patients with low PHT plasma concentrations that did not increase despite the administration of appropriate PHT doses have been reported, and the causes may include changes in plasma protein-binding rates, genetic mutations, and concomitant use of drugs that induce liver enzymes; however, even these factors do not explain the low PHT plasma concentrations in some cases. Case presentation: We encountered the case of a patient with plasma PHT concentrations that were continuously < 0.7 µg/mL after daily use of FOS for seizures that occurred after cardiopulmonary arrest. We analyzed the protein-unbound fraction, urinary metabolites, and related genes to investigate the cause. False negatives due to the measurement method, errors in dosage and administration method, and increased excretion of PHT were excluded. Hepatic metabolic activity of PHT increased to 4.6–6.1 times the normal level. The S/R ratio of 5-(p-hydroxyphenyl)-5-phenylhydantoin-glucuronide, a major PHT metabolite, was normal at 15.2, suggesting increased activities of CYP2C9 and CYP2C19. Furthermore, the protein-unbound fraction of PHT was 5.2–6.9%, CYP2C19*17 was wild type, and there was no concomitant drug use to induce both enzymes. Conclusions: The low PHT plasma concentration in this patient was found to be caused by increased hepatic metabolic activity that could not be explained by known factors. Careful monitoring is necessary to consider the possibility of increased hepatic metabolic activity in similar cases. [ABSTRACT FROM AUTHOR]

The essential oil of rosemary (Rosmarinus officinalis) (EORO) is widely used in folk medicine and has proven therapeutic effects. Our research evaluated high doses of rosemary essential oil in 54 Wistar rats between 180 and 200 g. The study consisted of three experiments: 1) behavioral monitoring of the animals after administration of 500 mg/kg i.p.; 2) electrocorticographic records after drug administration; 3) anticonvulsant drug reaction, where phenytoin, phenobarbital, and diazepam 10 mg/kg i.p were applied. The results showed that the application of EORO presented two phases. Phase 1 was characterized by the appearance of myorelaxation and a reduction in the power of the electrocorticogram in low-frequency cerebral oscillations. Phase 2 was characterized by increased excitability, with the appearance of convulsions and the increased power of electrocorticographic recordings in cerebral oscillations up to 40 Hz. In this phase, three tracing patterns were observed. Beta oscillations were the most prevalent and were better controlled by diazepam, which demonstrates that the excitatory activity of EORO is related to the reduction of GABAergic activity. [ABSTRACT FROM AUTHOR]

Layered double hydroxides (LDHs) are highly effective drug delivery systems, owing to their capacity to intercalate or adsorb biomaterials, flexible structure, swelling property, high stability, good biocompatibility, and ease of synthesis. Phenytoin (PHT) is an antiseizure BCS (Biopharmaceutics Classification System) class II drug, presenting low aqueous solubility. Therefore, the current study aimed at increasing its solubility, dissolution, and bioavailability. PHT was intercalated to the MgAl-LDH formed in situ and successful intercalation to form MgAl-PHT-LDH was confirmed by FTIR, PXRD, DSC, and TGA. Examination of particle size and morphology (by photon correlation spectroscopy and electron microscopy, respectively) confirmed the formation and intercalation of nanostructured LDH. Intercalation enhanced the saturation solubility of PHT at 25°C in 0.1N HCl and phosphate buffer (pH 6.8) by 6.57 and 10.5 times respectively. The selected drug excipient powder blend for the formulation of MgAl-PHT-LDH tablets exhibited satisfactory properties in both pre-compression parameters (angle of repose, bulk density, tapped density, Carr's index, and Hausner ratio) and tablet characteristics (weight variation, thickness, hardness, friability, content uniformity, and disintegration time). MgAl-PHT-LDH tablets showed better dissolution of PHT compared to unprocessed PHT tablets at all time points. Oral bioavailability of MgAl-PHTLDH tablets and unprocessed PHT tablets was tested in two groups of Sprague Dawley rats based on analysis of serum levels of both forms of PHT by UPLC-ESIMS/MS serum. MgAl-PHT-LDH tablets demonstrated a relative bioavailability of 130.15% compared to unprocessed PHT tablets, confirming a significantly higher oral bioavailability of MgAl-PHT-LDH. In conclusion, MgAl-PHT-LDH could provide a strategy for enhancing solubility, dissolution, and thereby bioavailability of PHT, enabling the evaluation of theclinical efficacy of MgAl-PHT-LDH tablets for the treatment of seizures at lower PHT doses. [ABSTRACT FROM AUTHOR]

The present research proposed the use of silver nanoprism in a fluorescent system for phenytoin determination in exhaled breath condensate samples. The fluorescence emission of luminol was quenched by energy transfer to silver nanoprism and then the phenytoin addition induced silver nanoprism aggregation, inhibited the fluorescence quenching of luminol, and resulted in recovery of the fluorescence intensity proportionally with phenytoin concentration. The experimental parameters were optimized using a one-at-a time method, and the method was partially validated according to FDA guideline. The validated method had a good analytical performance to detect phenytoin in the range of 0.01 to 2.0 µg.mL−1, with a detection limit of 0.005 µg.mL−1. [ABSTRACT FROM AUTHOR]

Phenytoin is a first-line antiepileptic drug with narrow therapeutic range and follows non-linear pharmacokinetics. Pharmacokinetics of phenytoin have been studied in plasma matrix before, however, there were several disadvantages. This study aimed to obtain partial validation data of the analytical method and the pharmacokinetic profile of phenytoin in Dried Blood Spot (DBS) of six healthy subjects. DBS has the advantage of only requiring small sample volumes and could be transported more efficiently. Phenytoin along with carbamazepine as the chosen internal standard was analyzed with a reversed-phase high performance-liquid chromatography system and a photodiode array detector at 205 nm. The results of partial validation, which evaluated the linearity, within-run accuracy, and precision, were within the criteria acceptance range. The pharmacokinetic profile showed that average AUC0-t was 83.81 ± 37.32 μg.h/mL and AUC0-∞ was 83.65 ± 38.89 μg.h/mL with an average ratio of 93%. Previous study quantifying phenytoin in the plasma matrix found the average AUC0-t was 39.41 ± 8.57 µg.h/mL and AUC0-∞ was 42.94 ± 9.55 µg.h/mL. Despite the difference between parameters of phenytoin analyzed in DBS and plasma matrices, the pharmacokinetic profiles obtained from both matrices were similar indicated by comparable concentration-time curves, thus, proving that DBS matrix can be used interchangeably with the plasma matrix as a more comfortable and effective alternative to phenytoin quantification in blood. [ABSTRACT FROM AUTHOR]

We developed a reliable high-performance liquid chromatographic analysis method using a relative molar sensitivity (RMS) technique that does not require an authentic, identical reference analyte material to quantify blood serum carbamazepine, phenytoin, voriconazole, lamotrigine, meropenem, mycophenolic acid, linezolid, vancomycin, and caffeine levels for routine blood concentration measurements. Carbamazepine and caffeine were also used as non-analyte reference materials to calculate the RMS of each analyte. The RMS was calculated from the ratio of the slope of the calibration equation (analyte/non-analyte reference material), then used to quantify analytes in control serum samples spiked with carbamazepine, phenytoin, voriconazole, meropenem, mycophenolic acid, linezolid or vancomycin. In addition, the concentrations of these six drugs in control serum samples determined by the proposed RMS method agreed well with that obtained using a conventional method. The proposed RMS method is a promising tool for the clinical determination of nine drugs, given the accuracy, precision, and efficiency of quantifying these analytes. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 24-year-old female diagnosed with familial encephalopathy with neuroserpin inclusion bodies (FENIB) who initially presented with catatonia, a rare manifestation of the condition. Topics discussed include the diagnostic challenges of distinguishing FENIB from other psychiatric disorders, the role of electroconvulsive therapy (ECT) in managing catatonic symptoms, and the impact of genetic findings on treatment and prognosis.

Purpose Nirmatrelvir/ritonavir is one of few options for outpatient treatment of COVID-19, but its use has been limited in transplant recipients due to significant drug interactions with immunosuppressants. Tacrolimus toxicity is possible when the drug is coadministered with nirmatrelvir/ritonavir and may require urgent reduction of tacrolimus levels. This case series describes the use of phenytoin for enzyme induction in 5 adult solid organ transplant recipients with supratherapeutic tacrolimus levels resulting from coadministration with nirmatrelvir/ritonavir. Summary Solid organ transplant recipients are at high risk for complications related to COVID-19. Outpatient treatment options are limited, and therapeutic drug monitoring is complex in patients requiring quarantine. The 5 solid organ transplant recipients described herein were initiated on nirmatrelvir/ritonavir in the outpatient setting and subsequently presented with supratherapeutic tacrolimus concentrations greater than 59 ng/mL and developed signs and symptoms of tacrolimus toxicity. In all patients, nirmatrelvir/ritonavir and tacrolimus were discontinued, and oral phenytoin (200-400 mg/day) was given for 2 to 4 days. Tacrolimus was resumed once tacrolimus levels decreased to appropriate levels. Conclusion These observations demonstrate that metabolism induction using phenytoin may be a useful strategy in the setting of supratherapeutic tacrolimus levels resulting from concomitant administration with nirmatrelvir/ritonavir. [ABSTRACT FROM AUTHOR]

The study aimed to perform a comprehensive in vitro and in vivo evaluation of a newly developed, patent-pending, powder-to-hydrogel, film-forming polymer complex base, which possesses tissue-protective and microbiome-supportive properties, and to compare its characteristics with poloxamer 407. The study used a combination of in vitro assays, including tissue viability and cell migration, and in vivo wound healing evaluations in male diabetic mice. Microbiome dynamics at wound sites were also analyzed. The in vitro assays demonstrated that the polymer complex base was non-cytotoxic and that it enhanced cell migration over poloxamer 407. In vivo, the polymer complex base demonstrated superior wound healing capabilities, particularly in combination with misoprostol and phenytoin, as evidenced by the reduced wound area and inflammation scores. Microbiome analysis revealed favorable shifts in bacterial populations associated with the polymer complex base-treated wounds. The polymer complex base demonstrates clinical significance in wound care, potentially offering improved healing, safety and microbiome support. Its transformative properties and efficacy in drug delivery make it a promising candidate for advanced wound care applications, particularly in chronic wound management. [ABSTRACT FROM AUTHOR]

Sexual dysfunction is common in men and women with neurological diseases. Medications used in neurology can cause sexual dysfunction independently of the disease process and this may adversely affect patients' quality of life. This review focuses on medications commonly prescribed to neurological patients that may contribute to altered sexual function, and discusses how they may differ in men and women. [ABSTRACT FROM AUTHOR]

Background: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate–severe traumatic brain injury (TBI). Methods: We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate–severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate–severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. Results: The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. Conclusions: Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate–severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence). [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the efficacy of transmucosal euthanasia solution to induce euthanasia. ANIMALS 6 bearded dragons (Pogona vitticeps). METHODS An initial dose of euthanasia solution containing pentobarbital and phenytoin sodium was administered transmucosally in conscious lizards (100 mg/kg pentobarbital dose), followed by a second dose 20 minutes later (400 mg/kg pentobarbital dose). The presence of movement, leakage of euthanasia solution, behaviors consistent with oral irritation, respiratory rate, heart rate, palpebral and corneal reflex, and response to noxious stimuli were recorded until death, confirmed by the absence of Doppler cardiac flow and cardiac electrical activity. The time to loss of all parameters was calculated. Postmortem evaluation allowed for histopathologic evaluation of the oral cavity and gastrointestinal tract to detect potential mucosal damage from the alkaline euthanasia solution. RESULTS The median time to death was 300 minutes (range, 300 to 360 minutes), median time to respiratory arrest was 30 minutes (range, 30 to 50 minutes), and median time to loss of deep pain response was 30 minutes (range, 20 to 50 minutes). Signs consistent with oral irritation occurred in 4 of 6 (66.7%) lizards, including 2 lizards that exhibited whole-body spasms after euthanasia solution administration. Histopathologic changes indicating peracute mucosal ulceration, suspected to be from caustic causes, were identified in 1 (1/6 [16.7%]) lizard. CLINICAL RELEVANCE Transmucosal euthanasia solution administration resulted in clinical euthanasia within 6 hours. This method should be utilized only after premedication with analgesic and/or anesthetic medications due to the potential for acute mucosal ulceration and behaviors that may be distressing in client-owned animals. [ABSTRACT FROM AUTHOR]

Background: Purple glove syndrome (PGS) is a rare condition characterized by limb edema, discoloration, and pain associated with intravenous and oral phenytoin administration. The pathophysiology is poorly understood, and there is no established treatment. Simple cases have previously been managed with hyaluronidase subcutaneous injections, with more severe cases resulting in compartment syndrome, debridement, or even amputation. Methods/Results: In this case report, a 2-year-old boy with status epilepticus developed PGS after receiving intravenous phenytoin via a cannula on the dorsum of the right hand. The patient was successfully managed by locally infiltrating subcutaneous hyaluronidase diffusely to the affected area, titrating its dose to effect, rather than aiming to adhere to any specific dosing limitation. The child was reviewed daily by the Plastic Surgery team until being discharged, and focal lesions began to demarcate after 48 hours, with epidermal loss but no deeper trauma. The epidermis peeled within one month, with healthy underlying skin found underlying when followed up in clinic. Conclusions: This case illustrates that subcutaneous administration of hyaluronidase and titrating to effect provides an effective and safe treatment for treating distal cases of early PGS in children. [ABSTRACT FROM AUTHOR]

Background: In otolaryngology practice, pediatric tonsillectomy is one of the most often done surgeries. We aimed to assess the short-term results of tonsillectomy alone versus tonsillectomy with local phenytoin with regard to postoperative pain, analgesia, bleeding and appetite. Methods: The study included in all 107 paediatric tonsillectomy patients; seven patients were excluded due to incomplete follow up only 100 patients completed follow up (60% female, 40% male, with age of (4-11 years) randomly chosen for tonsillectomy alone (group1 or TA; n = 50) and tonsillectomy with local phenytoin use (TPHT group, n = 50). Patient characteristics were recorded such as age, sex, and postoperative visual analogue scale (VAS), pain scores (2 hours postoperatively and first 10 days), appetite scores (first 7 days), also analgesia requirement (first 10 days) with documentation of bleeding complications. Results: From the third postoperative day, there was a noticeable decline in pain scores, which reached 0.0 ± 0.0.and on day 10 was 0.49± 0.79 in the TPHT and TA groups, respectively (p < 0.001 for each). comparing the TPHT group to the TA group, there were significant differences in pain and appetite scores from day 1 to day 10, as well as a decreased need for analgesia from day 1 to day 10. Additionally, there were few bleeding complications. Conclusion: The study of paediatric tonsillectomy patients proved effectiveness of local phenytoin use with tonsillectomy other than tonsillectomy without local phenytoin use. [ABSTRACT FROM AUTHOR]

Introduction: Severe acne breakouts often lead to atrophic acne scars, which affect millions of people worldwide and can significantly affect a person's self‐confidence and self‐image. Given the difficulty in treating atrophic acne scars, this study aims to investigate the efficacy of topical phenytoin in the treatment of atrophic acne scars. Method: This split face clinical trial on 25 patients between the ages of 18 and 40 involved the application of microneedling on one side of the face, with three sessions taking place over the course of a month. On the other side, a 1% phenytoin cream was administered three times daily for 1 week following the microneedling procedure. Baseline information was collected for all patients, and follow‐up assessments were conducted during the treatment sessions and 2 months after the last session. The assessments included evaluating the number and area of pores and spots, determining scar severity, assessing patient satisfaction, and recording any potential complications. Results: Among patients, 20 individuals (80%) were females, and the average age of the participants was 35.96 ± 9.23. In terms of the fine pore area, despite the fine pore count, both groups showed improvement over time (p: 0.03 vs. 0.06). Also, regarding large pore count and area, and the count and area of spots, both groups showed improvement over time (p: 0.001). However, there were no significant differences between the two groups (p > 0.05). On the other hand, when it comes to acne scar grade and patients' satisfaction, the phenytoin group outperformed the control group in all follow‐up sessions and this difference was found to be significant (p: 0.001). It is worth noting that no complications were observed among any of the patients. Conclusion: It appears that combining phenytoin cream with microneedling has a more effective therapeutic outcome in enhancing atrophic acne scars, when compared to microneedling alone, and this method can be regarded as a viable alternative in treating these types of scars. [ABSTRACT FROM AUTHOR]

Infantile Tremor Syndrome (ITS) is a complex neurological syndrome that affects exclusively breastfed infants, typically seen between 9 to 12 months of age. However, in the present case, it started at the ages of three months and four months, respectively. ITS is characterised by the presence of megaloblastic anaemia-like features, developmental regression, and the onset of tremors. Here, authors report two cases of ITS, whereby megaloblastic anaemia was present because of drug (phenytoin) intake in mothers. Phenytoin intake in mothers leads to low serum vitamin B12 levels in both the mother as well as the baby. Early onset of ITS in progeny has very rarely reported in the literature. Exclusive breastfeeding is generally considered nutritionally sufficient for infants below six months of age, and the onset of ITS is typically associated with the improper introduction of weaning foods beyond six months. However, in the present cases, although the babies were exclusively breastfed, they developed nutritional deficiencies that manifested as early onset ITS. Phenytoin intake and the associated vitamin B12 deficiency in the mothers are proposed as the causes of this presentation. Such an early presentation is also associated with severe pneumonia and was found to be fatal in one of the two reported causes. The authors would like to make a pertinent point that if pregnant mothers are taking any drugs that can lead to vitamin B12 deficiency, they should ideally be checked with relevant investigations and receive supplements if required, to prevent potentially fatal outcomes in their children. [ABSTRACT FROM AUTHOR]

Abstract The current study developed an innovative design for the production of smart multifunctional core-double shell superparamagnetic nanoparticles (NPs) with a focus on the development of a pH-responsive drug delivery system tailored for the controlled release of Phenytoin, accompanied by real-time monitoring capabilities. In this regard, the ultra-small superparamagnetic iron oxide@silica NPs (IO@Si MNPs) were synthesized and then coated with a layer of gelatin containing Phenytoin as an antiepileptic drug. The precise saturation magnetization value for the resultant NPs was established at 26 emu g-1. The polymeric shell showed a pH-sensitive behavior with the capacity to regulate the release of encapsulated drug under neutral pH conditions, simultaneously, releasing more amount of the drug in a simulated tumorous-epileptic acidic condition. The NPs showed an average size of 41.04 nm, which is in the desired size range facilitating entry through the blood–brain barrier. The values of drug loading and encapsulation efficiency were determined to be 2.01 and 10.05%, respectively. Moreover, kinetic studies revealed a Fickian diffusion process of Phenytoin release, and diffusional exponent values based on the Korsmeyer-Peppas equation were achieved at pH 7.4 and pH 6.3. The synthesized NPs did not show any cytotoxicity. Consequently, this new design offers a faster release of PHT at the site of a tumor in response to a change in pH, which is essential to prevent epileptic attacks.

Abstract Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation − hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.

Seizures are common after severe traumatic brain injury (TBI), with rates in the acute period approaching 5% with seizure prophylaxis in historical clinical trials. Post-traumatic seizures (PTS) are divided into categories: immediate PTS occur prior to resuscitation, typically in the field; early PTS occur from resuscitation to 7 days post-trauma; and late PTS occur thereafter. The relationship between immediate and early PTS, as well as their risk factors, are not well studied in modern cohorts. We performed a secondary analysis of a prospective database of severe TBI patients, defined as a post-resuscitation Glasgow Coma Scale ?8, from a single institution. For the 579 patients included, rates of immediate and early PTS were 1.6% and 3.8%, respectively. We were unable to identify any clinical correlates for immediate seizures. In contrast, early PTS were associated with age (odds ratio [OR] 1.5; 95% confidence interval [CI]: 1.1?2.0; p?0.01), hypoxia (3.3, 95% CI: 1.2?8.5; p?=?0.02), and subdural hematoma (SDH) (2.8, 95% CI: 1.0?2.8; p?=?0.04) in multivariable modeling. Patients with early PTS had higher rates of status epilepticus than those with immediate PTS (45% [n?=?10/22] vs. 0% [n?=?0/9]; p?=?0.03). This supports the notion of immediate PTS, which typically occur in the field and may not reliably be deciphered from pathological posturing responses, as an entity distinct from early PTS. Status epilepticus was highly morbid, associated with a 70% mortality rate. Our previously identified markers may help risk-stratify patients who may warrant longer monitoring with continuous electroencephalography to detect and treat early PTS and corresponding status epilepticus risk.

Background and purpose: Postoperative pain is one of the most important complications of anorectal surgeries. Management of these pains would result in improved situations and more satisfaction in patients. The utilization of topical medications is a recommended approach and phenytoin is a preferred option for this method. Hence, this study aimed to invstigate the effects of topical ointment of phenytoin 1%, topical placebo on wound healing, and postoperative pain in patients with perianal fistula after fistulotomy. Materials and methods: This study is a double-blind randomized clinical trial, it was conducted by the 31 codes of research ethics of Iran. In this double-blind randomized clinical trial, 44 patients with anal fistula underwent fistulotomy at Imam Khomeini Hospital in Sari after obtaining informed consent and were randomly selected to receive topical 1% phenytoin ointment or topical placebo twice a day. Phenytoin 1% cream was prepared by Iran Daropaksh Company and the placebo was prepared from Vaseline ointment. The inclusion and exclusion criteria of the study were checked. Medicines were coded in opaque medicine cans and assigned to study groups using a limited randomization method. After that, up to 8 weeks after the operation, pain, recovery, pain caused by defecation, itching, and complications were determined and compared in the groups. Data analysis was done with SPSS software (version 13.0). Chi-Square, Independent-Sample-T test, and Repeated-Measure ANOVA tests were used to compare between 2 groups. Results: A total of 44 patients completed the study and a thorough analysis was carried out. The average age in the intervention group was 43.0±11.8 years and in the control group was 42.1±6.9 years (P>0.05). The patients in the two study groups did not differ in terms of the type of fistula (P>0.05). Postoperative pain from the first to the fifth visit was significantly lower in the phenytoin group compared to the placebo group (P0.05). Wound secretion was observed in the phenytoin group and the control group, respectively, 63.6% and 68.2% (P>0.05). In the phenytoin group, 85.7% of serous and 14.3% of pus were observed, and in the control group, 53.3%, 33.3%, and 13.4% of serous, pus, and blood were observed, respectively (P>0.05). The only complication in the phenytoin group was bleeding, which was observed in 3 patients (13.6%). Conclusion: In general, it can be concluded that 1% phenytoin ointment is effective in wound healing and reducing postoperative pain in patients with anal fistula undergoing fistulotomy. Therefore, the use of this topical medicine is recommended. However, studies with a larger sample size are needed to reach more definitive results. (Clinical Trials Registry Number: IRCT2015041314483N4)

The current study developed an innovative design for the production of smart multifunctional core-double shell superparamagnetic nanoparticles (NPs) with a focus on the development of a pH-responsive drug delivery system tailored for the controlled release of Phenytoin, accompanied by real-time monitoring capabilities. In this regard, the ultra-small superparamagnetic iron oxide@silica NPs (IO@Si MNPs) were synthesized and then coated with a layer of gelatin containing Phenytoin as an antiepileptic drug. The precise saturation magnetization value for the resultant NPs was established at 26 emu g-1. The polymeric shell showed a pH-sensitive behavior with the capacity to regulate the release of encapsulated drug under neutral pH conditions, simultaneously, releasing more amount of the drug in a simulated tumorous-epileptic acidic condition. The NPs showed an average size of 41.04 nm, which is in the desired size range facilitating entry through the blood–brain barrier. The values of drug loading and encapsulation efficiency were determined to be 2.01 and 10.05%, respectively. Moreover, kinetic studies revealed a Fickian diffusion process of Phenytoin release, and diffusional exponent values based on the Korsmeyer-Peppas equation were achieved at pH 7.4 and pH 6.3. The synthesized NPs did not show any cytotoxicity. Consequently, this new design offers a faster release of PHT at the site of a tumor in response to a change in pH, which is essential to prevent epileptic attacks. [ABSTRACT FROM AUTHOR]

Gingival enlargement is a side effect of several different medication, including immunosuppressants, anticonvulsants, and calcium channel blockers. It is an inflammatory response that starts when plaque and calculus build up on the tooth surface. The most prevalent long-term neurological condition affecting people is epilepsy. In affluent nations, the prevalence of epilepsy is ~ 1%, whereas in less developed countries, it may >2%. The preferred medication for the condition, phenytoin, has major side effects include gingival enlargement. In addition to being visually disfiguring, this enlargement frequently affects speech, chewing and eating. Furthermore, those with poor dental hygiene, causes disabilities with motor coordination and muscular limitations leading to mental disability and physical impairments are more prone to periodontal disease. This article enlightened the mechanism of drug induced gingival enlargement clinically, microbiologically, and surgically. [ABSTRACT FROM AUTHOR]

This work presents a sensitive and accurate analytical method for the determination of phenytoin at trace levels in domestic wastewater and synthetic urine samples by gas chromatography-mass spectrometry (GC-MS) after the metal sieve-linked double syringe liquid-phase microextraction (MSLDS-LPME) method. A metal sieve was produced in our laboratory in order to disperse water-immiscible extraction solvents into aqueous media. Univariate optimization studies for the selection of proper extraction solvent, extraction solvent volume, mixing cycle, and initial sample volume were carried out. Under the optimum MSLDS-LPME conditions, mass-based dynamic range, limit of quantitation (LOQ), limit of detection (LOD), and percent relative standard deviation (%RSD) for the lowest concentration in calibration plot were figured out to be 100.5–10964.2 μg kg−1, 150.6 μg kg−1, 45.2 μg kg−1, and 9.4%, respectively. Detection power was improved as 187.7-folds by the developed MSLDS-LPME-GC-MS system while enhancement in calibration sensitivity was recorded as 188.0-folds. In the final step of this study, the accuracy and applicability of the proposed system were tested by matrix matching calibration strategy. Percent recovery results for domestic wastewater and synthetic urine samples were calculated as 95.6–110.3% and 91.7–106.6%, respectively. These results proved the accuracy and applicability of the proposed preconcentration method, and the obtained analytical results showed the efficiency of the lab-made metal sieve apparatus. [ABSTRACT FROM AUTHOR]