Intracerebral hemorrhage as the first symptomatic manifestation of chronic myeloid leukemia (chronic phase): A case report and literature review.

Background: Chronic myeloid leukemia (CML) is mostly asymptomatic at diagnosis. Intracerebral hemorrhage (ICH), as the first presentation of CML in its chronic phase (CP) has only once been reported in the literature. In addition, CML (CP) patients developing ICH are equally rare, with only eight cases reported. ICH is more commonly associated with CML progressing to its end stage (accelerated phase [AP] and blast crisis [BC]). The pathophysiology of ICH in CML-CP is postulated to be due to leukostasis, unlike in the CML-AP/BC, where thrombocytopenia and coagulopathy are the underlying mechanisms. This case adds to the scarce literature on a rare and challenging complication of ICH in CML-CP, especially as these patients tend to rebleed and management is uncertain. Case Description: A 22-year-old male presented with a 2-week history of headaches and vomiting, associated with a 1-week history of the left-sided weakness. Initial blood work revealed hyperleukocytosis. The patient was investigated for CML with intracranial involvement. During his stay, his Glasgow coma score (GCS) dropped (from 14 to 11), prompting an urgent CT scan which revealed a large resolving ICH with perifocal edema and midline shift. A decompressive hemicraniectomy with expansion duraplasty was performed to alleviate the mass effect and reduce intracranial pressure. Three hours postoperatively, the patient developed an extradural hematoma which needed prompt evacuation. A postoperative CT revealed an improved midline shift, and after 7 days, his GCS improved to 15, and he began oncological treatment. Neurological symptoms were experienced by our patient at presentation with hyperleukocytosis on full blood count, which may implicate leukostasis as an underlying mechanism. Conclusion: Even in the CP, CML patients presenting with mild neurological symptoms should be investigated to exclude intracranial bleeds. As these patients tend to rebleed, they should be conservatively managed unless there is a need to alleviate intracranial pressure.

Anti-amoebic effects of synthetic acridine-9(10H)-one against brain-eating amoebae.

Pathogenic A. castellanii and N. fowleri are opportunistic free-living amoebae. Acanthamoeba spp. are the causative agents of granulomatous amebic encephalitis (GAE) and amebic keratitis (AK), whereas Naegleria fowleri causes a very rare but severe brain infection called primary amebic meningoencephalitis (PAM). Acridinone is an important heterocyclic scaffold and both synthetic and naturally occurring derivatives have shown various valuable biological properties. In the present study, ten synthetic Acridinone derivatives (I-X) were synthesized and assessed against both amoebae for anti-amoebic and cysticidal activities in vitro. In addition, excystation, encystation, cytotoxicity, host cell pathogenicity was also performed in-vitro. Furthermore, molecular docking studies of these compounds with three cathepsin B paralogous enzymes of N. fowleri were performed in order to predict the possible docking mode with pathogen. Compound VII showed potent anti-amoebic activity against A. castellanii with IC50 53.46 µg/mL, while compound IX showed strong activity against N. fowleri in vitro with IC50 72.41 µg/mL. Compounds II and VII showed a significant inhibition of phenotypic alteration of A. castellanii, while compound VIII significantly inhibited N. fowleri cysts. Cytotoxicity assessment showed that these compounds caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 µg/mL, while also effectively reduced the cytopathogenicity of Acanthamoeba to HaCaT cells. Moreover, Cathepsin B protease was investigated in-silico as a new molecular therapeutic target for these compounds. All compounds showed potential interactions with the catalytic residues. These results showed that acridine-9(10H)-one derivatives, in particular compounds II, VII, VIII and IX hold promise in the development of therapeutic agents against these free-living amoebae.

Outcome of surgical treatment for neglected congenital muscular torticollis: A series of 28 adolescent patients.

Background: Congenital muscular torticollis (CMT) is a common musculoskeletal anomaly that can be excellently managed at birth with conservative physiotherapy; as a result, literature on neglected cases of CMT in older patients is sparse, and there is controversy regarding the ideal surgical approach. This report aims to provide the outcome of 28 adolescent patients with neglected CMT who underwent unipolar release at the distal sternocleidomastoid muscle (SCM). Methods: Twenty-eight adolescent patients with untreated CMT presented to our department between 2016 and 2019 and underwent unipolar release at the distal end of their SCM. All patients had no other anomaly based on clinical examination and radiological investigations. At the time of surgery, the mean age of patients was 15.8 years (range 13-18 years). There were 10 male and 18 female patients with the right side affected in 20 cases. All patients were followed up for 2 years. Patients were evaluated using an adapted version of the modified Lee's scoring system to assess cosmesis and the cervical-mandibular angle (CMA) to assess radiological change. Results: The adapted modified Lee's scoring system indicated 17 patients (60.7%) had an excellent outcome, 6 patients (21.4%) had a good outcome, and 5 patients (17.9%) had a fair outcome. In particular, scarring was fine in 23 patients (82.1%) and only slight in the remaining. Independent to the categorical outcome, all patients subjectively reported high satisfaction with their cosmesis. The preoperative mean CMA was 19.6° (range, 8.5-31.5°), which was reduced to a mean of CMA of 14.0° (range, 3-28°) after surgery (P < 0.05). No patient developed any permanent complication or required surgery for recurrence. No serious postoperative complications such as infection or hematoma were observed. Conclusion: In uncomplicated cases of neglected CMT in adolescent patients, unipolar tenotomy of the distal SCM is a safe and reliable technique with good clinical outcomes.

Insulinotropic action of 2, 4-dinitroanilino-benzoic acid through the attenuation of pancreatic beta-cell lesions in diabetic rats.

Beta cell destruction plays a key role in the pathogenesis of type 1 diabetes mellitus. It has also been argued that beta-cell mass is compromised in some cases of type 2 diabetes, although this is still debated. Currently, the failure of oral antidiabetic insulin secretagogue drugs to properly manage type 2 diabetes demands novel approaches for the treatment of this condition. The aim of the present study was to investigate the in vitro and in vivo antidiabetic effect in STZ-induced diabetic rats, and maximum tolerated dose (MTD) safety of novel anthranilic acid derivative, 2, 4-dinitroanilino-benzoic acid (1). Anthranilic acid derivative 1 was also evaluated for insulinotropic action on STZ-mediated pancreatic beta-cell lesions in diabetic rats. During an eight week study, oral glucose tolerance test, fasting blood glucose, and serum insulin levels, and pancreatic insulin contents were measured in four different groups of Wistar rats; control, STZ-induced diabetic, gliclazide-treated, and anthranilic acid derivative-treated diabetic rats. Beta-cell number and islet area were also quantified, and immunohistochemical study was performed. In vitro studies in cells showed that 2, 4-dinitroanilino-benzoic acid (1) did not adversely effect the cells viability. We found that the derivative 1 significantly improved the glucose tolerance, fasting blood glucose, and HbA1c levels, serum insulin levels, and pancreatic insulin contents (P < 0.05), comparable to gliclazide-treated group. The derivative 1 exhibited a significant insulinotropic action on diabetic pancreas, and caused an increased immunoreactivity for insulin, as compared to gliclazide-treated group. Together these results suggest that treatment of diabetic rats with 2, 4-dinitroanilino-benzoic acid (1) improved the glucose tolerance, fasting blood glucose, and HbA1c levels most probably by restoring the functional activities of the pancreas via its insulinotropic action. This indicates that the derivative 1 can serve as lead for the treatment of diabetes caused by low insulin levels.