Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2- {[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity

The discovery of novel acyclic amide cannabinoid-1 receptor inverse agonists is described. They are potent, selective, orally bioavailable, and active in rodent models of food intake and body weight reduction. A major focus of the optimization process was to increase in vivo efficacy and to reduce the potential for formation of reactive metabolites. These efforts led to the identification of compound 48 for development as a clinical candidate for the treatment of obesity.     

An unusual cause of left ventricular outflow tract obstruction

Left ventricular outflow tract obstruction (LVOTO) has been reported with bio-prosthetic and mechanical mitral valves (MV), though it is more common with the former. The obstruction can be dynamic or fixed. We hereby report a case of fixed LVOTO following bio-prosthetic MV replacement (MVR).     

Patterns of lingual tissue deformation associated with bolus containment and propulsion during deglutition as determined by echo-planar MRI

Disordered lingual function is a common clinical attribute of patients with oropharyngeal dysphagia. To determine physiologic patterns of lingual tissue motion during swallowing, we imaged the actively deforming tongue during water bolus swallows with sequential single-slice sagittal orientation echo-planar imaging. At rest, with the bolus contained in the oral cavity before swallow initiation, the tongue displayed a characteristic curved configuration consisting of a convex surface (anterior to the bolus) in continuity with a concave surface (containing the bolus) and a posterior-located convex surface (comprising the tongue base). With swallow initiation, the previously deformed tongue underwent rapid biphasic displacement: (a) superior displacement of the anterior tongue and deepening of the midposterior-located bolus-containing concavity, resulting in a laterally beveled surface encompassing the bolus; and (b) retrograde displacement of the configured tissue, resulting in clearance of the bolus from the oral cavity to the oropharynx. These findings indicate that deglutitive tongue action can be depicted by echo-planar imaging as a series of deformative surface modifications, which are related to the activity of intrinsic and extrinsic lingual muscles.     

Nonfamilial hyperphosphatemic tumoral calcinosis with ulnar neuropathy

We present a case of multiple large juxta-articular painless masses involving both the elbows and right hip in a 27-year old south Asian male who presented with ulnar neuropathy and constitutional symptoms. Radiology, blood investigations and biopsy confirmed it to be hyperphosphatemic tumoral calcinosis. Patient was also diagnosed with an extremely rare association, testicular microlithiasis. Complete surgical excision with low phosphate diet resulted in complete neurological recovery and no recurrence at 30 months. Tumoral calcinosis should be considered in the differential diagnosis of a case with multiple, symptomatic juxta-articular masses.     

Echo-Planar Magnetic Resonance Imaging of Deglutitive Vocal Fold Closure: Normal and Pathologic Patterns of Displacement

Abnormalities of vocal fold closure during deglutition predispose to aspiration due to impairment of airway protection. Conventional assessment of deglutitive vocal fold motion with laryngoscopy does not permit visualization through a complete adduction-abduction cycle. We determined spatiotemporal patterns of deglutitive vocal fold adduction through echo-planar magnetic resonance imaging in 15 normal volunteers and 6 patients with vocal fold paralysis. In normal volunteers, deglutitive vocal fold adduction was synchronized with laryngeal elevation, with complete vocal fold closure at the apex. Patients with unilateral vocal fold paralysis demonstrated reduced elevation and medial movement of the involved vocal fold. At maximal laryngeal elevation the uninvolved vocal fold attained a position superior to the paralyzed fold, resulting in level differences and an interglottic gap. Patients with bilateral vocal fold paralysis demonstrated reduced elevation and medial movement of both vocal folds. These findings indicate that normal and abnormal patterns of vocal fold displacement can be distinguished noninvasively through the use of echo-planar imaging. Laryngoscope, 106:568-572, 1996     

A case of reversible dilated cardiomyopathy due to acromegaly with partial empty sella

Acromegaly has several cardiovascular manifestations of which cardiomyopathy (CMP) and hypertension (HTN) are important and contribute to the increased mortality associated with the disease. Both these manifestations are reversible with treatment. However, very advanced CMP with severe systolic dysfunction has low likelihood of reversal. The reversibility is higher in young population and decreases as age advances. Also, the time required for these manifestations to resolve is about 1 year. Here, we describe a case in which HTN and advanced heart failure resolved in an aged patient within a very short span of 2 months from the time of presentation.     

Ensuring precision in lower limb deformity correction through a combination of temporary external fixation followed by internal fixation: Results of a retrospective study

Background:

It is important to plan preoperatively when contemplating internal fixation following deformity correction. Surgeons often find it difficult to retain the achieved correction till the end of internal fixation. To maintain precise correction we used hybrid technique which uses both external and internal fixation. The objective of the study was to evaluate the effectiveness of this hybrid technique in achieving and retaining desired correction.

Materials and Methods:

In this retrospective study, we evaluated the magnitude of deformity with radiological parameters. We compared correction which was planned and correction which was achieved. The technique was used during surgery for corrective osteotomies. Before carrying out the osteotomy, rail fixator with two swivel clamps was applied. After osteotomy swivel clamps were loosened. Desired correction was achieved. While fixator held the fragments in corrected position, definitive internal fixation was carried out. External fixator was removed after completion of internal fixation. Position of mechanical axis ratio, mechanical lateral distal femoral angle and mechanical medial proximal tibial angle were measured before and 12 weeks after surgery. Student t-test was used to analyze the difference between correction which was planned and correction which was achieved.

Results:

There was no statistical difference between the desired correction and the correction achieved.

Conclusions:

Temporary use of external fixator while correcting angular deformities of lower limb allows to achieve accurate correction.     

Maternal pseudo-Bartter syndrome associated with severe perinatal brain injury

Background

Maternal electrolyte imbalance is rarely reported as causative factor of severe perinatal brain injury.

Case characteristics

This case outlines a unique maternal and neonatal pseudo-Bartter syndrome presented with metabolic alkalosis and hypochloremia due to maternal severe vomiting.

Observation

Neonatal MRI brain revealed extensive brain hemorrhages with porencephalic cysts. Subsequent investigation workup points towards maternal severe metabolic alkalosis as its cause.

Message

Careful medical attention should be paid to pregnant women with excessive vomiting to ensure a healthy outcome for both the mother and the baby.