Investigation of Mechanistic Pathway for Trimethyl Borate Mediated Amidation of (R)-Mandelic Acid for the Synthesis of Mirabegron, an Antimuscarinic Agent.

The present work describes investigation of mechanistic pathway for trimethyl borate mediated amidation of (R)-mandelic acid (3) with 4-nitophenylethylamine (2) to provide (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide (4) during mirabegron synthesis. Plausible reaction mechanism is proposed by isolating and elucidating the active α-hydroxy ester intermediate 16 from the reaction mass. Trimethyl borate mediated approach proved to be selective in providing 4 without disturbing α-hydroxyl group and stereochemistry of the chiral center, and is also a greener, more economic and production friendly over the reported methods. The developed approach is rapid and efficient for the preparation of 4 with an overall yield of 85-87% and around 99.0% purity by HPLC at scale.

Efficacy of palatal block for analgesia following palatoplasty in children with cleft palate.

BACKGROUND: This prospective randomized controlled study was undertaken to evaluate the efficacy of palatal block i.e. blocking of naso palatine, greater and also lesser palatine nerves in children with cleft palate undergoing palatoplasty by evaluating its effects on intraoperative anesthetic requirement, postoperative analgesia and parental satisfaction. METHODS: Forty-five pediatric patients aged below five undergoing cleft palate repair were randomly allocated to three groups of 15 each. After tracheal intubation, Group NB received no block for control, group S received 0.5 ml of normal saline and group B received 0.5 ml of 0.25% bupivacaine for palatal block. Postoperative pain score, the time to first demand of analgesia and number of rescue analgesic demands were noted. Finally, the parental satisfaction was graded. RESULTS: The block had no anesthetic sparing effect. The mean pain scores were significantly lower in patients who received block than in the group NB. The mean area under curve for FLACC score in group NB was 29 with 95% CI of 25-32, group S was 15 with 95% CI of 8.9-22.3 and in group B, it was 10 with 95% CI of 6-14. The time to first demand of analgesia was 6 [4.5-6] h in group NB, 18 [6-18] h in group S and 18 [18-18] h in group B (P-0.000). The number of demands of rescue analgesia was significantly less in group B 0 [0-0.25], 0 [0-2] in S group compared to group NB 3 [3-3] (P-0.000). The parental satisfaction was good in patients who received block and poor in group NB. CONCLUSION: Palatal block is technically simple, safe and effectively provides postoperative analgesia with good parental satisfaction. Injection of saline also produced palatal nerve block; however, the effect was not consistent.

Appraisal of transverse nasal groove: a study.

BACKGROUND: Transverse nasal groove is a condition of cosmetic concern which awaits due recognition and has been widely described as a shallow groove that extends transversely over the dorsum of nose. However, we observed variations in the clinical presentations of this entity, hitherto undescribed in literature. AIMS: We conducted a clinicoepidemiological study of transverse nasal lesions in patients attending our outpatient department. METHODS: We conducted a prospective observational study. We screened all patients attending our out-patient department for presence of transverse nasal lesions, signs of any dermatosis and associated other skin conditions. RESULTS: One hundred patients were recruited in the study. Females (80%) predominated over males. Most patients were of 15-45 years age group (70%). Majority of the transverse nasal lesions were classical transverse nasal groove (39%) and others included transverse nasal line (28%), strip (28%), ridge (4%) and loop (1%). Seborrhoeic diathesis was the most common condition associated with transverse nasal lesion. CONCLUSIONS: Occurrence of transverse nasal line, strip, ridge and loop, in addition to classical transverse nasal groove implies that latter is actually a subset of transverse nasal lesions. Common association of this entity with seborrheic dermatitis, seborrhea and dandruff raises a possibility of whether transverse nasal lesion is a manifestation of seborrheic diathesis.

Hepatic pulmonary fusion: a rare case.

This paper describes a rare case of a seven-month-old infant with right-sided congenital diaphragmatic hernia, who was found to have fusion of his herniated part of liver with lower lobe of right lung. The report describes clinical presentation and successful surgical management along with a review of the world literature.

Presence of alpha-1-antitrypsin in pancreatic carcinoma. Report of four cases in association with hepatic storage of the protease inhibitor.

Among 13 patients with accumulation of alpha-1-antitrypsin (AAT) globules in periportal hepatocytes, 4 were found to have a pancreatic malignant tumor. Three tumors presented features of well-differentiated adenocarcinoma, the fourth was a poorly differentiated carcinoma displaying a glandular differentiation in its lymph node metastases. AAT immunoreactivity was detected in tumor cells from all 4 cases in either the primary or metastatic site. Two tumors contained Grimelius-positive cells; most of them were also positive for AAT. In addition, AAT immunoreactivity was observed in cells from normal large excretory ducts of the pancreas. AAT-positive tumor cells were negative on staining for other normal plasma (e.g. albumin and fibrinogen) or tissue-associated proteins (e.g. alpha-fetoprotein and human chorionic gonadotrophin). The findings appear to suggest: the pancreas adenocarcinoma as an additional malignant tumor with AAT positivity; a possible malignant proliferation of AAT containing cells in the pancreas ducts; a possible association between AAT accumulation in the liver and pancreatic adenocarcinoma.