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Rhabdomyolysis is associated with patients presenting to the emergency department who test positive for cocaine on rapid drug screening, including those neither agitated nor restrained. The aim was...

Introduction: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP mAb), is a migraine-specific treatment for migraine prevention.Areas covered: This review will briefly discuss other available and emerging CGRP mAbs and the neurophysiology of fremanezumab. The review will focus on phase III trials of the efficacy of fremanezumab for episodic and chronic migraine, and a recent pooled safety and tolerability analysis of its use.Expert opinion: Continued efficacy and safety data collection will help guide long-term risk and efficacy counseling in the general population.

The disproportionate prevalence of migraine among women in their reproductive years underscores the clinical significance of migraine during pregnancy. This paper discusses how migraine evolves during pregnancy, secondary headache disorders presenting in pregnancy and puerperium, and acute and preventive options for migraine management during pregnancy and lactation. Migraine is influenced by rising estrogen levels during pregnancy and their sharp decline in puerperium. Migraine, and migraine aura, can present for the first time during pregnancy and puerperium. There is also a higher risk for the development of preeclampsia and cerebrovascular headache during these periods. New or refractory headache, hypertension, and abnormal neurological signs are important "red flags" to consider. This paper reviews the diagnostic utility of neuroimaging studies and the risks of each during pregnancy. Untreated migraine can itself lead to preterm delivery, preeclampsia, and low birth weight infants. Behavioral interventions and lifestyle modifications are the cornerstone for migraine treatment during pregnancy. In addition, one should consider the risks and efficacy of each treatment during pregnancy on an individual basis. The protective nature of breastfeeding for migraine is debated, but there is no evidence to suggest breastfeeding worsens migraine. Acute and preventive migraine treatment options are available for nursing mothers. Neuromodulation and neurostimulation devices are additional options for treatment during pregnancy and lactation, while the safety of using calcitonin gene-related peptide receptor antagonists during these times remains to be determined.

Antiepileptic drugs (AEDs) are an important class of agents used in the treatment of migraine, a neurological disorder that imparts significant socioeconomic burden. It is important for neurologists to understand the rationale for AEDs in migraine-preventive treatment, as well as each agent’s efficacy and tolerability profile, in order to best determine clinical care. This article specifically provides the following: (1) a review of the mechanism of action, efficacy, and tolerability of topiramate and divalproex sodium/sodium valproate, the most widely used AEDs for migraine prevention, (2) a discussion on emerging evidence regarding the efficacy of zonisamide and levetiracetam, and (3) comments on gabapentin, pregabalin, carbamazepine, oxcarbazepine, and lamotrigine, AEDs which have insufficient evidence for use in migraine prevention. The potential role for new extended-release formulations of topiramate in migraine prevention is discussed. There is substantial evidence supporting the use of AEDs in migraine prevention. Specific agents should be chosen based on their efficacy and tolerability profiles. Further studies are needed to determine the efficacy of the newer AEDs, zonisamide and levetiracetam, in migraine prevention and to clarify the role of gabapentinoids in headache management.

Histone deacetylases (HDACs) have been implicated in a number of diseases including cancer, cardiovascular disorders, diabetes mellitus, neurodegenerative disorders and inflammation. For the treatment of epigenetically altered diseases such as cancer, HDAC inhibitors have made a significant progress in terms of development of isoform selective inhibitiors. Isoform specific HDAC inhibitors have less adverse events and better safety profile. A HDAC isoform i.e., HDAC2 demonstrated significant role in the development of variety of diseases, mainly involved in the cancer and neurodegenerative disorders. Discovery and development of selective HDAC2 inhibitors have a great potential for the treatment of target diseases. In the present compilation, we have reviewed the role of HDAC2 in progression of cancer and neurodegenerative disorders, and information on the drug development opportunities for selective HDAC2 inhibition.

Phosphodiesterase 10A is a member of Phosphodiesterase (PDE)-superfamily of the enzyme which is responsible for hydrolysis of cAMP and cGMP to their inactive forms 5'-AMP and 5'-GMP, respectively. PDE10A is highly expressed in the brain, particularly in the putamen and caudate nucleus. PDE10A plays an important role in the regulation of localization, duration, and amplitude of the cyclic nucleotide signalling within the subcellular domain of these regions, and thereby modulation of PDE10A enzyme can give rise to a new therapeutic approach in the treatment of schizophrenia and other neurodegenerative disorders. Limitation of the conventional therapy of schizophrenia forced the pharmaceutical industry to move their efforts to develop a novel treatment approach with reduced side effects. In the past decade, considerable developments have been made in pursuit of PDE10A centric antipsychotic agents by several pharmaceutical industries due to the distribution of PDE10A in the brain and the ability of PDE10A inhibitors to mimic the effect of D2 antagonists and D1 agonists. However, no selective PDE10A inhibitor is currently available in the market for the treatment of schizophrenia. The present compilation concisely describes the role of PDE10A inhibitors in the therapy of neurodegenerative disorders mainly in psychosis, the structure of PDE10A enzyme, key interaction of different PDE10A inhibitors with human PDE10A enzyme and recent medicinal chemistry developments in designing of safe and effective PDE10A inhibitors for the treatment of schizophrenia. The present compilation also provides useful information and future direction to bring further improvements in the discovery of PDE10A inhibitors.

Migraine is a prevalent disease with a substantial socioeconomic impact. However, stigma affects social attitude toward migraine, accruing additional burden on individuals with migraine and isolating them from a society that should be supporting them. PURPOSE OF THIS REVIEW: This review will discuss the following concepts: (1) the emergence of stigma toward migraine and its impact on medical care; (2) internalized stigma among those with migraine and its detrimental effect on quality of life and patient-physician relationships; (3) the structural impact of stigma on research funding, workplace support, and specialized care; and (4) strategies for "rebranding" the disease and alleviating stigma toward migraine. RECENT FINDINGS: Recent literature on condition rebranding offers strategies on how to define and communicate migraine to the public. Rebranding of migraine to alleviate societal stigma is paramount. This involves use of unified language, education, and advocacy.

Author(s): Richards, John R; Stayton, Taylor L; Wells, Jason A; Parikh, Aman K; Laurin, Erik G | Abstract: OBJECTIVE:Determine differences between faculty, residents, and nurses regarding night shift preparation, performance, recovery, and perception of emotional and physical health effects. METHODS:Survey study performed at an urban university medical center emergency department with an accredited residency program in emergency medicine. RESULTS:Forty-seven faculty, 37 residents, and 90 nurses completed the survey. There was no difference in use of physical sleep aids between groups, except nurses utilized blackout curtains more (69%) than residents (60%) and faculty (45%). Bedroom temperature preference was similar. The routine use of pharmacologic sleep aids differed: nurses and residents (both 38%) compared to faculty (13%). Residents routinely used melatonin more (79%) than did faculty (33%) and nurses (38%). Faculty preferred not to eat (45%), whereas residents (24%) preferred a full meal. The majority (g72%) in all groups drank coffee before their night shift and reported feeling tired despite their routine, with 4:00 a.m. as median nadir. Faculty reported a higher rate (41%) of falling asleep while driving compared to residents (14%) and nurses (32%), but the accident rate (3% to 6%) did not differ significantly. All had similar opinions regarding night shift-associated health effects. However, faculty reported lower level of satisfaction working night shifts, whereas nurses agreed less than the other groups regarding increased risk of drug and alcohol dependence. CONCLUSION:Faculty, residents, and nurses shared many characteristics. Faculty tended to not use pharmacologic sleep aids, not eat before their shift, fall asleep at a higher rate while driving home, and enjoy night shift work less.

Migraine is a disabling and prevalent neurological disease, commonly affecting women during their reproductive years. It is crucial for providers to be able to adequately counsel women who are pregnant, planning pregnancy, or nursing, regarding preventive and abortive treatment options for episodic migraine. This review will discuss (1) the expected course of migraine during pregnancy and the post-partum period, (2) recommended preventive therapies for migraine during pregnancy and lactation, and (3) recommended abortive medications for migraine during pregnancy and lactation. Recent research has indicated safety for triptan use during pregnancy and ibuprofen use during the first trimester of pregnancy. Considerations for use of emerging migraine-preventive treatment, such as non-invasive neurostimulators, are discussed. For clinical decision-making and patient counseling, it is important to understand both the limitations in determining teratogenic effects in humans and the principles affecting medication transmission from mother to breast milk.

A 48-year-old female patient with end-stage renal failure developed unexplained severe lactic acidosis (LA) associated with hyperglycemia during robotic-assisted laparoscopic renal transplantation. Initial treatment with sodium bicarbonate and insulin infusion were ineffective in treating acidemia. Postoperatively, intravenous administration of thiamine resulted in rapid improvement of LA and blood sugar levels. Uremia and chronic hemodialysis might be the causes behind the quantitative/qualitative deficiency of thiamine unmasked during the surgical stress. Though a rare entity, acute thiamine deficiency should be considered in the differential diagnosis of unexplained severe LA in patients with chronic kidney disease and hemodialysis who undergo major surgery or admitted to critical illness care units.

The purpose of this review is to introduce the non-pediatric radiologist to the many common conditions that can be diagnosed via pediatric magnetic resonance imaging (MRI), particularly in the emergency setting. The vast majority of radiologic examinations in children occurs in non-pediatric facilities, and is interpreted by non-pediatric radiologists. Therefore, it is essential that the non-pediatric radiologist is aware of the current and potential imaging trends occurring in the pediatric setting, largely focused on increased MRI utilization. With advances in MR technology, many MRIs can be performed relatively quickly, eliminating the need for sedation. Because of this, and its lack of ionizing radiation, pediatric MRI has been increasingly relied upon in the emergency setting over the past decade. It is ever more prudent that every radiologist familiarize him or herself with the varying MR studies that can be performed after hours, and the MR appearance of common diagnoses. Our review focuses on the more common conditions diagnosed via MR imaging including appendicitis, other causes of right lower quadrant pain, shunted hydrocephalus, limited sequence brain MR in the acute setting, musculoskeletal infections and spine emergencies. With the continued advent of faster MRI scanners and avoidance of ionizing radiation, the usage of MRI in the pediatric setting will only increase in the future. We believe that it is important that every radiologist become familiar and comfortable in interpreting the common conditions that can be diagnosed via MRI.

Evaluating postoperative patients with hardware is challenging following surgical intervention for hip maladies such as femoral neck fractures and slipped capital femoral epiphysis (SCFE). These children are at increased risk of developing avascular necrosis, and imaging may be requested to confirm or exclude this diagnosis. Children with Legg-Calve-Perthes disease can be monitored for restoration of blood flow to the capital femoral epiphysis to guide management and help with prognosis. Although MRI is sensitive for detecting early avascular necrosis, the presence of hardware degrades image quality. This report examines the utility of bone scans for evaluating femoral head perfusion in children who have undergone surgery for femoral neck fractures, SCFE or Legg-Calve-Perthes disease. A retrospective review of 20 patients (22 scans) after fixation for femoral neck fracture, SCFE or Legg-Calve-Perthes disease from 2012 to 2015 was performed. The bone scan findings were correlated with the intraoperative findings or clinical follow-up. Twenty-one of the 22 (95%) bone scans in 19 of the 20 (95%) patients demonstrated findings consistent with clinical outcomes and/or the intraoperative appearance of the femoral head. Four of 20 patients (20%) had bone scan features of avascular necrosis, defined as “absent” or “moderately diminished” femoral head activity, which were confirmed intraoperatively and resulted in poor outcomes. Radionuclide imaging of hips in the postoperative setting is a valuable modality for assessing the risk of avascular necrosis, a complication of femoral neck fractures and SCFE and for evaluating the restoration of flow to the capital femoral epiphyses of children with Legg-Calve-Perthes disease.

Excluding ethanol, cannabis is the most commonly used drug in the United States and worldwide. Several published case series and reports have demonstrated an association between cannabis use and acute coronary syndrome (ACS). We report the first ever published case of ACS precipitated by cannabis use that was confirmed with concomitant rising quantitative plasma levels of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol, a secondary metabolite of cannabis. A 63-year-old non-tobacco smoking male with no prior medical history presented to the emergency department with chest pain immediately after smoking cannabis, and anterior ST-segment elevation pattern was observed on his electrocardiogram. He was taken to the cardiac catheterization lab for percutaneous coronary intervention (PCI) of his left anterior descending artery, whereupon he developed hemodynamically significant accelerated idioventricular rhythm necessitating intra-aortic balloon pump placement. He underwent two further PCI procedures during his inpatient stay and was discharged in improved condition after eight days. Two sequential quantitative plasma cannabis metabolite assays at time of arrival then 6 h later were 24 ng/mL then 39 ng/mL, an increase of 63%, which implicated the patient's acute cannabis use as a precipitant of ACS. We also discuss the putative pharmacologic mechanisms behind cannabis use and ACS. Clinicians caring for patients using cannabis who have vascular disease and/or risk factors should be aware of this potentially deleterious association, as cessation of cannabis use could be important for their cardiac rehabilitation and long-term health.

Purpose: To describe a loop suture technique that allows intraoperative conjunctival closure and later optional suture adjustment in strabismus surgery in uncooperative patients. Materials and Methods: This retrospective case series comprised 25 patients. After a recessed or resected horizontal muscle was secured to the sclera with a primary suture suspended back 2 mm, a second loop suture was passed through the body of the muscle and under the primary suture knot. The loop suture could be removed later while the patient was awake, or it could be tied to advance the muscle. Success was defined as a residual deviation of 10 prism diopters (PD) or less at 2 months postoperatively. Results: In the study cohort, 20 patients had successful alignment at 2 months (80%). Six patients (24%) underwent postoperative suture tightening by the loop technique, and each muscle affected the alignment an average of 7.7 PD (±3.8 PD). No patients underwent a reoperation within the first 2 months. One patient had a pyogenic granuloma (4%). Conclusions: The loop suture technique permits optional postoperative tightening of muscles and avoids sedation in children or uncooperative patients not requiring adjustment.

Management of successful pregnancy after renal transplantation is a unique challenge to nephrologist, obstetrician, and anesthesiologist, as these patients have altered physiology and are immune-compromised. We present the anesthetic management of three postrenal transplant patients scheduled for cesarean section. While conducting such cases, cardiovascular status, hematological status, and function of transplanted kidney should be assessed thoroughly. Side effects of immunosuppressant drugs and their interaction with anesthetic agents should be taken into consideration. Main goal of anesthetic management is to maintain optimum perfusion pressure of renal allograft to preserve its function.

Vasopressin is often used locally to reduce blood loss during surgery. Vasopressin has longest clinical effect, but its systemic effects may be profound and pose significant challenges for the anesthesiologist and it can also sometimes cause lethal complications. The loss of peripheral pulse along with bradycardia, non-measurable arterial blood pressure, and cardiac complications have been reported after myometrial injection of vasopressin. Here, we describe a patient with multiple uterine myomas who developed severe bradycardia, non-measurable blood pressure by non-invasive means and loss of peripheral pulse after myometrial injection of vasopressin at a total dose of 20 units (1 unit/ml) with documentation of severe peripheral arterial vasospasm and increased proximal blood pressure. The patient was successfully resuscitated.

Non-cardiogenic pulmonary edema (NCPE) is a clinical syndrome characterized by simultaneous presence of severe hypoxemia, bilateral alveolar infiltrates on chest radiograph, without evidence of left atrial hypertension/congestive heart failure/fluid overload. The diagnosis of drugrelated NCPE relies upon documented exclusion of other causes of NCPE like gastric aspiration, sepsis, trauma, negative pressure pulmonary edema. We describe a 28year-old, 50 kg male with ASA risk III posted for laparoscopic renal transplantation, who developed NCPE after 4 hours of administration of rabbit anti-human thymocyte immunoglobulin (ATG). He was successfully treated with mechanical ventilatory support and adjuvant therapy. This report emphasizes that this fatal complication may occur with use of ATG.

Purpose: Based on in vitro and on clinical evidence of protection against acute side effects of radiation, a prospective randomized, open study was performed to determine the efficacy of an oral proteolytic enzyme preparation in patients with head and neck cancer receiving conventional fractionated radiation therapy. Methods: Patients with stage T3/T4 head and neck cancer were eligible. One hundred patients from two centres were entered into the study. 60Co gamma-radiation was delivered at a standard daily radiation dose of 2 Gy in 25–35 fractions over a period of 6–7 weeks. Two lateral parallel opposing fields were used with a portal area of 10 × 15 cm. Patients assigned to the test group arm additionally received enzyme tablets orally t.i.d. starting 3 days prior to radiation therapy, and continuing up to 5 days after completion of the course of radiation therapy. Patients in the control arm were not given any drug or placebo. Acute radiation side effects were described as mucositis, skin reaction, dysphagia, and were graded at each visit during and after radiation therapy, following RTOG/EORTC criteria. Results: The severity (maximum extent) of acute radiation therapy side effects was significantly less in enzyme-treated patients than in control patients: mucositis (mean: 1.3 vs 2.2, P

Differentiated carcinoma of the thyroid has good prognosis, even in patients presenting in the late stage and with distant metastasis. In India, the incidence of papillary carcinoma and follicular carcinoma are in the ratio of 60∶40. A retrospective study was carried out to determine the impact of patient and tumor factors on survival, and to develop a simple rish group staging system to predict survival in patients with differentiated thyroid carcinomas. Four hundred and seventeen (417) patients undergoing primary treatment at our hospital between 197–1985, were entered to the study. There were 198 follicular carcinomas and 219 papillary carcinomas. Impact of patient and tumor variables were studied by drawing Kaplan Meier curves and comparing them by the Chi Sq Test. Age

DNA chip arrays hold considerable promise for diagnostic sequencing of polymerase chain reaction (PCR) products. To date, however, arrays have been relatively expensive, complex to use and difficult to interpret, preventing their adaptation to the clinical lab. A moderate density array method has been developed that enables efficient, easy-to-interpret and robust solid-phase PCR product sequencing. Here, the results of Mycobacterium tuberculosis rifampin resistance mutation detection by primer-extension-based sequence scanning of the rpo B gene of M. tuberculosis are presented. Rifampin resistant clinical isolates were identified in as little as 1 h post PCR amplification with visual results detection.

Background: Laparoscopic donor nephrectomy is a routine practice since 1995. Until now, the recipient has always undergone open surgery for transplantation. In our institute, laparoscopic kidney transplantation (LKT) started in 2010. To facilitate this surgery, the patient must be in steep Trendelenburg position for a long duration. Hence, we decided to study the effect of CO2 pnuemoperitoneum and Trendelenburg position in chronic renal failure (CRF) patients undergoing LKT. Methods: A total of 20 adult CRF patients having mean age of 31.7±10.36 years and body mass index 19.65±3.41 kg/m 2 without significant coronary artery disease were selected for the procedure. Cardiovascular parameters heart rate (HR), mean arterial pressure (MAP), Central venous pressure (CVP) and respiratory parameters (ETCO 2 , peak airway pressure) were noted at the time of induction, after induction, 15 min after creation of pnuemoperitoneum, 30 min after Trendelenburg position, 15 min after decompression of pnuemoperitonuem and after extubation. Arterial blood gas analysis was carried out after induction, 15 min after creation of pnuemoperitoneum, 30 min after Trendelenburg position and 15 min after clamp release. Total duration of surgery, anastomosis time, time for the establishment of urine output and total urine output were noted. Serum creatinine on the 1 st and 7 th post-operative day were recorded. Results: Significant increase in HR was observed after creation of CO 2 pneumoperitoneum and just before extubation. Significant increase in the MAP and CVP was noted after creation of pneumoperitoneum and after giving Trendelenburg position. No significant rise in the ETCO 2 and PaCO 2 was observed. Significant increase in the base deficit was observed after the clamp release, but none of the patients required correction. Conclusion: LKT performed in steep Trendelenburg position with CO 2 pneumoperitoneum significantly influenced cardiovascular and respiratory homeostasis; however, measured parameters remained within clinically acceptable range without affecting early function of the transplanted kidney.

Medicinal plants have played an important role in treating and preventing a variety of diseases throughout the world. Metabolic syndrome had become a global epidemic, defined as a cluster of three of five criteria: insulin resistance and glucose intolerance, abdominal obesity, hypertension, low high-density cholesterol, and hypertriglyceridemia. The current review focuses on Indian medicinal plant drugs and plants used in the treatment of diabetes and hyperlipidemia. Though there are various approaches to reduce the ill-effects of diabetes and hyperlipidemia and its secondary complications, plant-based drugs are preferred due to lesser side effects and low cost. The current review focuses on twenty-three medicinal plants used in the treatment of Diabetes mellitus and nine medicinal plants used in the treatment of hyperlipidemia. The wealth of knowledge on medicinal plants points to a great potential for research and the discovery of new drugs to fight diseases, including diabetes and hyperlipidemia.

Background It was observed that new presentations of anaplastic carcinoma of the thyroid had become infrequent in the last two decades. Methods All cases of thyroid cancer seen at our centre between 1969–1993 (n = 2921) were classified as papillary 49%, follicular 34%, medullary 7.5%, anaplastic 4.7%, and other 4.8%. The total number of thyroid cancers show a 3.5-fold rise. Results The differentiated thyroid cancers show a significant rising trend as against the relative proportion of anaplastic carcinoma, which shows a significant decline (P = 0.002). Clinicopathologic data on 124 patients of anaplastic carcinoma revealed 50% patients had either long-standing goitres, previous thyroid abnormalities, or associated differentiated thyroid carcinoma on histology. Conclusions The decline in the relative proportion of anaplastic carcinoma may in part be explained by the clinicopathologic findings or it may be attributed to histological reclassification. © 1996 Wiley-Liss, Inc.

OBJECTIVE : In this report, we evaluate the recurrence- and progression-free survival of patients with meningiomas involving the cavernous sinus. METHODS : The rates of tumor recurrence and progression in 119 patients with meningiomas involving the cavernous sinus treated between 1983 and 1993 were analyzed. RESULTS : The mean follow-up period was 33.8 months. There were seven recurrences of completely resected tumors (7 of 73, 10%) and seven progressions of incompletely resected tumors (7 of 46, 15%). Life table analysis of recurrence- and progression-free survival was performed. The recurrence-free survival rate was 94% at 3 years and 81% at 5 years. In contrast, the progression-free survival rate was 87% at 3 years and 62% at 5 years (P = 0.0456). There were two patterns of recurrence or progression. The first group of tumors had an aggressive biological behavior with growth at multiple areas of resection ; the second group showed growth at or near the margins of resection. Functional status continued to improve slowly during the follow-up period ; however, there was no statistically significant difference between the Karnofsky scores obtained 3 to 12 months postoperatively and the follow-up Karnofsky scores (obtained >1 yr postoperatively). CONCLUSION : Surgery for meningiomas involving the cavernous sinus seems to provide excellent tumor control. Our experience suggests that for the majority of these tumors, complete tumor resection can be performed with acceptable risks of morbidity and mortality and seems to increase the duration of recurrence-free survival. The long-term quality of life of surviving patients is satisfactory, with the great majority of the patients being independent.

Background Prognostic parameters for papillary carcinoma of the thyroid have been defined by several groups. However, no such study has been reported for follicular carcinoma. Methods We undertook a retrospective study of well-differentiated carcinoma of the thyroid operated at the Tata Memorial Hospital during the period 1970–1985. In our series, follicular carcinoma formed 48% of the well-differentiated carcinomas of the thyroid. The variables age, sex, size, extrathyroidal spread, distant metastases, and lymph node metastases were evaluated. The survival was plotted according to the Kaplan-Meier method, and graphs compared by log-rank test. Univariate and multivariate analyses were performed. Results Based on our experience we stratified the cases into low-risk and high-risk groups. The low-risk group included: age below 40 years, tumor size less than 5 cm, and no extrathyroidal extension or metastases. This low risk group had 100% survival at 15 years, compared with 40% survival for the high-risk group (P < .001). Seventy-three percent (73%) of our cases were in the high-risk group. Conclusions Based on our findings that the majority of our patients were in the high-risk group, we advocate a total or near-total thyroidectomy in treatment of follicular carcinoma of the thyroid. There is a need to arrive at a universally acceptable classification of risk groups in follicular carcinoma of the thyroid gland. HEAD & NECK 1996;18:118–126 © 1996 John Wiley & Sons, Inc.

Background. Cancer of the alveolo-buccal complex even when locally advanced is amenable to curative resection. However, the extent of lymph node dissection remains controversial. Methods. A total of 181 patients with T3/T4 cancer of the alveolo-buccal complex who underwent a radical neck dissection (RND) were analyzed retrospectively to determine the incidence and pattern of lymph node involvement and to define the extent of neck dissection required in these cancers. Results. Lymph node involvement was as follows: level I (85%), II (51%), III (19%), IV (18%), V (5%). Levels I and II were most commonly involved (94%). Skip metastases occurred in 13%. Levels IV and V were involved in 2% and 20% when levels I, II, and III were uninvolved and involved, respectively. Conclusion. A supraomohyoid neck dissection (SOHD) should be performed and subjected to a frozen section evaluation in every patient. If lymph nodes are negative, then SOHD is adequate. If levels I, II, or III are positive, then a RND should be performed. © 1995 Jons Wiley & Sons, Inc.

Cancer of the oral tongue is a common disease. Thirty five (35%) percent of patients seen at our hospital are in Stages I&II. The choice of surgical treatment is a wide excision of the lesion (WE) or a hemiglossectomy (HG). This study was carried out to compare the local recu-rrences and survival in patients undergoing either a WE or HG for early cancer of the tongue. One hundred and twenty six (126) patients were evaluated, 40 underwent a WE and 86 HG. The local recurrence was higher in the WE group, 25% compared with 9% in the HG group; which is statistically significant (p=0.02). This was also seen in the Tl subgroup (p=0.003). Survival were better in the HG group (p=0.005), which was also seen for the Tl subgroup (p=0.004). Our study demonstrates that there is a lower incidence of local recurrences following a hemiglossectomy for Tl-2 tumours of the oral tongue with improved survivals. Our recommendation is that hemi-glossectomy should be the optimal surgery performed for early cancer of the oral tongue.

In the final report of a prospective, randomized controlled clinical trial, we report the results of using adjuvant perioperative chemotherapy in patients with oral cancer. Our study is based on the hypothesis of Goldie and Coldman. A total of 135 patients with alveolobuccal carcinoma, classified as clinically stage III and IV, were entered on the protocol. After a curative resection, they were randomized. The patients in the test arm of the study received methotrexate 50 mg/m2 on the 3rd, 10th, and 17th postoperative days. The patients in the control arm underwent observation. This analysis at 24 months showed a disease-free survival rate of 61% in the test arm versus 37% in the control arm, which is statistically highly significant (P0.01). Analysis of the recurrence pattern showed that recurrence at the primary site was dramatically reduced during the first 6 postoperative months (P = 0.002). Our study provided further clinical evidence in support of the concepts of Goldie and Coldman that the timing of chemotherapeutic drugs is critical for a successful end result.

A retrospective analysis of 127 surgically treated cases of T-1, T-2 carcinoma of oral tongue during the period 1987-1990 was undertaken. 68.5 per cent (87) underwent hemiglossectomy and 31.5 per cent (40) underwent wide excision. There were loco-regional recurrences in 22 per cent (27). In the hemiglossectomy group 9 per cent (8 of 87) had local recurrences compared to 25 per cent (10 of 40) of wide excision group, (P = 0.01). Mean disease free survival was 40 months and 33 months for hemiglossectomy group and wide excision group respectively, (P = 0.006). It is seen that local recurrences are significantly less for the hemiglossectomy group compared to the wide excision group.

We have demonstrated that subjects with complex regional pain syndrome (CRPS) have asymmetric venous pool plasma concentrations of norepinephrine (NE) when affected and unaffected limbs are compared, with most demonstrating decreased NE levels in the affected limb. This pilot study explored whether systemic venous plasma catecholamine levels in CRPS subjects with sympathetically maintained pain (SMP) differ from those found in healthy volunteers. We also explored whether catecholamine levels were correlated with scores on psychometric measures of depression, anxiety, and personality. Venous blood samples from 33 CRPS/SMP patients (from unaffected limbs) and 30 healthy control subjects were assayed for plasma NE and epinephrine (E) concentrations. Plasma NE levels were significantly higher in the CRPS group (P < 0.001). Statistical comparisons of E levels across groups did not achieve significance (P < 0.06), although 52% of CRPS/SMP patients had E levels exceeding the 95% confidence interval based on control data. Significant positive correlations were found between E levels and scores on the Beck Depression Inventory and Scales 1, 3, and 6 on the Minnesota Multiphasic Personality Inventory-2 (all P < 0.05). This preliminary work suggests that increased NE and E levels in CRPS/SMP patients may result from the pain of CRPS, consequent affective distress, or both. Alternatively, our findings could reflect premorbid adrenergic hyperactivity caused by affective, endocrine, or other pathology, which might predispose these individuals to develop the syndrome. Definitive studies are needed to examine these hypotheses in detail.

Introduction: EGFR targeted therapies like Tarceva are very effective initially for non-small cell lung cancer (NSCLC) harboring EGFR activating mutations; but patients eventually develop resistance to these first line inhibitors and in about 50% of the cases, resistance is due to a secondary mutation T790M,leading to decreased affinity of these drugs. In such cases, drugs targeting this secondary mutation will be quite beneficial in improving the quality of life. Also, such drugs could potentially delay the onset of resistance in patients with EGFR activating mutation. In this context, we’ve developed a series of potent small molecule inhibitors (Pyrimidine derivatives) that target EGFR-activating (Exon 19 del and L858R) and resistance mutations and are very selective against wild type EGFR. Methods: TR-FRET Biochemical assay was performed for assessing the in-vitro enzymatic potency. Cell based mechanistic and functional assays like EGFR autophos assay, cell proliferation and apoptotic assays were used to assess the cellular potency of these inhibitors. HCC827 and xenograft models were used to assess in vivo target engagement and efficacy. Results: One of the compounds from this series, JIEM-0186, had an IC50 of 0.004 uM against EGFR T790M mutation in the in vitro TR-FRET assay. In cells carrying EGFR activating mutation (HCC827), this compound showed an IC50 of 0.012 uM that is comparable to Tarceva (0.005 uM). In H1975 cells carrying the EGFRT790M mutation, JIEM-0186 had a potency of 0.009 uM in inhibiting cell proliferation. Further JIEM-0186 showed remarkable selectivity against cells carrying wild type EGFR (>200 fold). Afatinib, a pan EGFR inhibitor, has been shown to have an IC50 of 0.09 uM against EGFRT790M with comparable potency on cells carrying wild type EGFR (Li et al., 2008). JIEM-0186 also showed very good selectivity for EGFR over other kinases. In in vivo pharmacokinetics (PK) studies in mice, JIEM-0186 showed good exposure and half life for adequate target coverage. JIEM-0186 showed excellent target engagement in inhibiting EGFR autophos in H1975 xenograft with an ED80 of about 40 mg/kg. JIEM-0186 also showed strong efficacy in H1975 xenograft accounting for 61, 71 and 86 % tumor growth inhibition at 12.5, 25 and 50 mg/kg, BID, PO dosing compared to vehicle control. In mice, MTD of JIEM-0186 was higher than 1000 mg/kg and was well tolerated upon consecutive dosing at 100 mg/kg, PO for 14 days. We are currently evaluating additional compounds from this and another series with similar potency and better PK properties as potential back-ups. Conclusion: JIEM-0186 and other compounds from this series have the promise to be developed as novel, efficacious and selective small molecule inhibitors for NSCLC with EGFR-activating and resistant mutations, which is still a high unmet medical need. Citation Format: Dhanalakshmi Sivanandhan, Payal K. Parikh, Avinash Sheshachalam, Chandregowda V, Rajagopal Bhakthavatchalam, Manish Gupta, Sanjeev Giri, Krishnakumar V. Potent, novel small molecule inhibitors targeting EGFR L858R/T790M mutation for non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-232. doi:10.1158/1538-7445.AM2014-LB-232

Laryngo-tracheal stenosis is a difficult problem to treat by conservative means, because of recurrent stenosis and failures of different treatment modalities. The carbondioxide laser has improved the outlook of this problem and it has been effectively utilized alone or in conjunction with adjuvant therapy like stents, interstitial steroids, etc. We present here our experience with carbondioxide laser, used as a single modality in the treatment of laryngo-tracheal stenosis.

The pathogenesis of Osler's nodes and Janeway lesions has been disputed since their first description more than 100 years ago. Hypersensitivity vasculitis has been suggested, whereas others have sought to prove that septic microemboli are the cause. Little histologic evidence has been provided, however, to confirm the suspicion that the skin lesions in acute bacterial endocarditis are secondary to septic emboli. We describe a patient with fulminant methicillin-resistant Staphylococcus aureus endocarditis and skin lesions that cultured the same organism. Histologic examination revealed gram-positive cocci in clusters and chains within the lumen of vessels.

e15115 Background: A Phase III clinical trial (NCT00321620) recently demonstrated that denosumab delayed time to 1st skeletal-related event (SRE) and subsequent SREs longer than zoledronic acid (ZA), but showed no difference in either survival or disease progression between the two products. The objective of this study was to conduct an economic evaluation of denosumab compared to ZA in the treatment of bone metastases in men with hormone-refractory prostate cancer. Methods: A Markov model was developed to assess the one-year costs and effectiveness associated with the two treatments. Transition probabilities associated with experiencing the first SRE, subsequent SREs, disease progression, and death were primarily derived from the results of the Phase-III clinical trial, and, supplemented with published literature. Costs associated with progression, SREs, adverse events, and death were obtained from the literature and estimated as paid amounts in 2010 dollars. The model results include theincremental cost...

Tracheal rupture occurred in 7 of 174 (4%) patients undergoing laryngopharyngectomy with gastric transposition. Tracheal tears were classified as proximal if they involved the upper two-thirds of the trachea (five patients), or distal if they extended into the lower one-third of the trachea (two patients) and their clinical features and management analyzed. Predisposing factors, including prior radiotherapy (three patients) and preoperative tracheostomy (1 patient) did not influence the site or severity of tracheal injury. Proximal tears were detected incidentally in four patients, but in one patient, manifested postoperatively with subcutaneous emphysema and pneumothorax. Distal tears manifested dramatically with a ventilatory leak. Adequate access for repair of distal tears may necessitate a right thoracotomy while proximal tears may be sutured through the cervical incision. Gastric transposition alone did not prevent air leak in two patients. Postoperative complications included prolapse of the stomach and bilateral pneumothoraces in one patient. Close interaction between the surgeon and the anesthesiologist ensured a successful outcome in six patients. There was one mortality.

Primary adenocarcinoma of the esophagus is uncommon and the incidence in the middle third of the esophagus is rare, accounting for about 0.7%-1.5% of cases. Metastasis of carcinoma to the eye is a rare occurrence. We report here a case of primary adenocarcinoma of the middle third of the esophagus with choroidal metastasis. © 1993 Wiley-Liss, Inc.

The dilemma of increasing costs of medical care and shrinking health budgets has stimulated attempts to implement stricter control on expenditure without affecting the quality of care. This study shows that in patients with operable breast cancer, a policy of early discharge after a mastectomy did not have deleterious effects on wound healing and was well accepted by patients. In a randomized trial, drains were removed after either 3 or 6 days postmastectomy, and in both groups of patients there was no difference between the mean volumes of seromas aspirated or the number of aspirations and return visits to the hospital. This suggests that a policy of early discharge is safe, acceptable, economical, and may improve bed utilization. © 1992 Wiley-Liss, Inc.

This is an interim report of a study of perioperative adjuvant chemotherapy following radical surgery for oral cancer, based on the hypothesis of Goldie and Coleman. 135 patients of alveolobuccal carcinoma, clinically stage III and IV, were entered on the protocol. After a curative resection, they were randomized. The test arm received methotrexate 50 mg/m2 on the 3rd, 10th, and 17th postoperative days. The control arm was only observed. This analysis at 12 months showed a disease free survival of 71% in the test arm vs. 45% in the control arm, which is statistically highly significant (P less than 0.01). Analysis of recurrence pattern showed that recurrence at the primary site was dramatically reduced during the first 6 postoperative months (P less than 0.01). Our study provided further clinical evidence in support of the concepts of Goldie and Coleman that the timing of chemotherapeutic drugs is very critical for a successful end result.