A Comparison of Vitamin A and Leucovorin for the Prevention of Methotrexate-Induced Micronuclei Production in Rat Bone Marrow

INTRODUCTION: Methotrexate, a folate antagonist, is a mainstay treatment for childhood acute lymphoblastic leukemia. It is also widely used in a low dose formulation to treat patients with rheumatoid arthritis. In rats, methotrexate is known to induce micronuclei formation, leading to genetic damage, while vitamin A is known to protect against such methotrexate-induced genetic damage. Leucovorin (folinic acid) is generally administered with methotrexate to decrease methotrexate-induced toxicity. OBJECTIVES: We aimed to determine whether vitamin A and leucovorin differed in their capacity to prevent formation of methotrexate-induced micronuclei in rat bone marrow erythrocytes. The present study also aimed to evaluate the effect of combined treatment with vitamin A and leucovorin on the formation of methotrexate-induced micronuclei. METHODS: Male and female Wistar rats (n=8) were injected with 20 mg/kg methotrexate (single i.p. dose). The control group received an equal volume of distilled water. The third and fourth groups of rats received vitamin A (5000 IU daily dose for 4 successive days) and leucovorin (0.5 mg/kg i.p. dose for 4 successive days), respectively. The fifth and sixth groups of rats received a combination of vitamin A and a single dose of methotrexate and a combination of leucovorin and methotrexate, respectively. The last group of rats received a combination of leucovorin, vitamin A and single dose of methotrexate. Samples were collected at 24 hours after the last dose of the treatment into 5% bovine albumin. Smears were obtained and stained with May-Grunwald and Giemsa. One thousand polychromatic erythrocytes were counted per animal for the presence of micronuclei and the percentage of polychromatic erythrocyte was determined. RESULTS: Comparison of methotrexate-treated rats with the control group showed a significant increase in the percentage of cells with micronuclei and a significant decrease polychromatic erythrocyte percentage. Combined methotrexate and vitamin A therapy and combined methotrexate and leucovorin therapy led to significant decreases in the micronuclei percentage and an increase in polychromatic erythrocyte percentage when compared to rats treated with methotrexate alone. Leucovorin was found to be more effective than vitamin A against the formation of methotrexate-induced micronuclei. CONCLUSIONS: Both vitamin A and leucovorin provided significant protection against genetic damage induced by methotrexate

A study of anatomical variability of the omohyoid muscle and its clinical relevance

OBJECTIVE: The omohyoid muscle is a long, thin muscle consisting of superior and inferior bellies and an intermediate tendon, which runs obliquely in the lateral cervical region. The omohyoid is important in neck dissections because it is the surgical landmark for level III and IV lymph node metastases. METHODS: In the present study, the anterior and posterior triangle of the neck was dissected in 35 male cadavers and observed for variations in the omohyoid bilaterally. Observations were focused on variations in number, attachments, and position of omohyoid. RESULTS: Among the 35 cadavers studied, double omohyoid was present in one cadaver, inferior belly originated from the clavicle in three cadavers, superior belly merged with the sternohyoid in two cadavers, and the omohyoid received additional slips from the sternum in one cadaver. Standard attachment and position of the omohyoid was observed in the remaining cadavers. CONCLUSION: Variations of this muscle are important because of its close relation to the large vessels and brachial plexus. Because of the direct adhesion of the intermediate tendon to the anterior wall of the internal jugular vein and its connection with it through a thin lamina of the pretracheal layer of the cervical fascia, the contraction of the omohyoid muscle has a direct effect on the lumen of this vessel

Anatomical Variation of Radial Wrist Extensor Muscles: A Study in Cadavers

OBJECTIVE: The tendons of the extensor carpi radialis longus and brevis muscles are quite useful in tendon transfer, such as in correction of finger clawing and restoration of thumb opposition. Knowledge of additional radial wrist extensor muscle bellies with independent tendons is useful in the above-mentioned surgical procedures. METHODS: The skin, subcutaneous tissue, and antebrachial fascia of 48 (24 on the right side and 24 on left side) male upper limb forearms were dissected. The following aspects were then analyzed: (a) the presence of additional muscle bellies of radial wrist extensors, (b) the origin and insertion of the additional muscle, and (c) measurements of the muscle bellies and their tendons. RESULTS: Five out of 48 upper limbs (10.41%) had additional radial wrist extensors; this occurred in 3 out of 24 left upper limbs (12.5%) and 2 out of 24 right upper limbs (8.3%). In one of the right upper limbs, two additional muscles were found. The length and width of each additional muscle belly and its tendon ranged between 2 - 15cm by 0.35 - 6.4cm and 2.8 - 20.8cm by 0.2 0.5cm, respectively. The additional radial wrist extensor tendons in our study basically originated either from the extensor carpi radialis longus or brevis muscles and were inserted at the base of the 2nd or 3rd metacarpal bone. CONCLUSION: The present study will inform surgeons about the different varieties of additional radial wrist extensors and the frequency of their occurrence

Entrapment of the Martin-Gruber branch of median nerve in the forearm

We report a rare case of a dual neuro-vascular variation, which was observed in the right extremity of male cadaver. About an inch inferior to the elbow joint, three branches arose from the median nerve. These were the anterior interosseous branch, a Martin-Gruber branch (MGB) and a muscular branch. The MGB coursed infero-medially to join with the ulnar nerve by running posterior to the ulnar artery. It was surprising to observe that the MGB passed between the ulnar artery and its venae comitantes. There was an acute angulation of the MGB here, suggesting entrapment at this site

Atypical insertion of the abductor pollicis longus muscle, an anatomical case report

During a routine dissection of upper limb in the Department of Anatomy, we came across an unusual attachment of the abductor pollicis longus muscle. Proximal fleshy belly of it originated from the dorsal surface of the shaft of the radius as usual. As it descended it split into two tendons (lateral and medial) proximal to the wrist. The medial tendon attached to the lateral side of base of the first metacarpal bone, whereas the lateral tendon again converted into a fleshy belly at its distal part and inserted into the proximal phalanx of the thumb overlapping the insertion of the abductor pollicis brevis. Double tendons of abductor pollicis longus, each inserting separately into different sites is a rare incidence and needs to be reported to enhance the success rate of any surgical procedures at this region

A study of anatomical variability of the omohyoid muscle and its clinical relevance

OBJECTIVE: The omohyoid muscle is a long, thin muscle consisting of superior and inferior bellies and an intermediate tendon, which runs obliquely in the lateral cervical region. The omohyoid is important in neck dissections because it is the surgical landmark for level III and IV lymph node metastases. METHODS: In the present study, the anterior and posterior triangle of the neck was dissected in 35 male cadavers and observed for variations in the omohyoid bilaterally. Observations were focused on variations in number, attachments, and position of omohyoid. RESULTS: Among the 35 cadavers studied, double omohyoid was present in one cadaver, inferior belly originated from the clavicle in three cadavers, superior belly merged with the sternohyoid in two cadavers, and the omohyoid received additional slips from the sternum in one cadaver. Standard attachment and position of the omohyoid was observed in the remaining cadavers. CONCLUSION: Variations of this muscle are important because of its close relation to the large vessels and brachial plexus. Because of the direct adhesion of the intermediate tendon to the anterior wall of the internal jugular vein and its connection with it through a thin lamina of the pretracheal layer of the cervical fascia, the contraction of the omohyoid muscle has a direct effect on the lumen of this vessel

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Extent of knowledge and attitudes on plagiarism among undergraduate medical students in South India - a multicentre, cross-sectional study to determine the need for incorporating research ethics in medical undergraduate curriculum

BACKGROUND: Undergraduate medical students in India participate in various research activities However, plagiarism is rampant, and we hypothesize that it is the lack of knowledge on how to avoid plagiarism. This study’s objective was to measure the extent of knowledge and attitudes towards plagiarism among undergraduate medical students in India. METHODS: It was a multicentre, cross-sectional study conducted over a two-year period (January 2018 – December 2019). Undergraduate medical students were given a pre-tested semi-structured questionnaire which contained: (a) Demographic details; (b) A quiz developed by Indiana University, USA to assess knowledge; and (c) Attitudes towards Plagiarism (ATP) questionnaire. RESULTS: Eleven medical colleges (n = 4 government medical colleges [GMCs] and n = 7 private medical colleges [PMCs]) participated. A total of N = 4183 students consented. The mean (SD) knowledge score was 4.54 (1.78) out of 10. The factors (adjusted odds ratio [aOR]; 95% Confidence interval [CI]; p value) that emerged as significant predictors of poor knowledge score were early years of medical education (0.110; 0.063, 0.156; < 0.001) and being enrolled in a GMC (0.348; 0.233, 0.463; < 0.001).The overall mean (SD) scores of the three attitude components namely permissive, critical and submissive norms were 37.56 (5.25), 20.35 (4.20) and 31.20 (4.28) respectively, corresponding to the moderate category. CONCLUSION: The overall knowledge score was poor. A vast majority of study participants fell in the moderate category of attitude score. These findings warrant the need for incorporating formal training in the medical education curriculum

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention