"Craniofacial and dental manifestations of a case of Proteus syndrome"

Proteus syndrome, which is a reference to the ancient Greek god Proteus, the Polymorphous, was called to the attention of pediatricians. Recognition of this syndrome has been difficult because of the variability of the syndrome's manifestations and because of its rarity. We describe a rare case of Proteus syndrome and we discuss its differential diagnosis. Our case presents with hemi facial hypertrophy, scrotal tongue, enamel hyperplasia as well as differential in the size of the dentition on both sides of the arch.     

Update on zona pellucida glycoproteins based contraceptive vaccine

Zona pellucida (ZP) glycoproteins, due to their critical role in mammalian fertilization, have been proposed as candidate immunogens for development of a contraceptive vaccine. Active immunization studies in a variety of animal species, employing either native or recombinant zona proteins, has established their contraceptive potential. Hence, ZP glycoprotein-based contraceptive vaccines have a very good potential for controlling wild life population. To make it a realistic proposition, additional research inputs are required to develop new potent adjuvants and novel practical strategies for vaccine delivery. The observed ovarian dysfunction, often associated with immunization by ZP glycoproteins, is one of the major obstacles for their application in the control of human population. Ongoing studies to delineate epitopes of ZP glycoproteins that will generate an immune response capable of inhibiting fertility without any untoward effects on ovarian functions will help in determining their feasibility for human use.     

Prophylactic phenytoin does not improve cerebral edema or survival in acute liver failure--a controlled clinical trial

BACKGROUND/AIMS: Seizure activity in patients with acute liver failure (ALF) may increase cerebral oxygen requirements and worsen cerebral edema. Recently, prophylactic phenytoin has been recommended to suppress sub-clinical seizure activity evident on electroencephalographic monitoring. To determine the clinical utility of prophylactic phenytoin therapy in patients with ALF. METHODS: Forty two patients with ALF were randomized. Twenty two patients were given prophylactic phenytoin and 22 patients acted as controls. The baseline clinical and biochemical features were similar in the two groups and patients with > or =2 poor prognostic variables were equally represented. RESULTS: Sixteen patients in the phenytoin group, and 15 in the control group developed cerebral edema (P=0.38). Mechanical ventilation was required in 10 and 12 patients in the phenytoin and control groups, respectively, (P=0.77). Seizures occurred in 5 (22.7%) control patients and 5 (25%) phenytoin treated patients (P=0.86). Fourteen (70%) patients randomized to phenytoin and 15 (68.2%) control patients died (P=0.89). CONCLUSIONS: Seizure was common in patients with ALF. Prophylactic use of phenytoin did not prevent cerebral edema, seizures or need for mechanical ventilation, and did not improve survival.     

Assessment of tracheal intubating conditions in children using remifentanil and propofol without muscle relaxant

BACKGROUND: Tracheal intubation in children can be achieved by deep inhalational anaesthesia or an intravenous anaesthetic and a muscle relaxant, suxamethonium being widely used despite several side-effects. Studies have shown that oral intubation can be facilitated safely and effectively in children after induction of anaesthesia with propofol and alfentanil without a muscle relaxant. Remifentanil is a new, ultra-short acting, selective mu-receptor agonist that is 20-30 times more potent than alfentanil. This clinical study was designed to assess whether combination of propofol and remifentanil could be used without a muscle relaxant to facilitate tracheal intubation in children. METHODS: Forty children (5-10 years) admitted for adenotonsillectomy were randomly allocated to one of two groups to receive remifentanil 2 microg.kg(-1) (Gp I) or remifentanil 3 microg.kg(-1) (Gp II) before the induction of anaesthesia with i.v. propofol 3 mg.kg(-1). No neuromuscular blocking agent was administered. Intubating conditions were assessed using a four-point scoring system based on ease of laryngoscopy, jaw relaxation, position of vocal cords, degree of coughing and limb movement. Mean arterial pressure (MAP) and heart rate (HR) measured noninvasively before induction of anaesthesia to 5 min after intubation (seven time points). RESULTS: Tracheal intubation was successful in all patients without requiring neuromuscular blocking agent. Intubating conditions were clinically acceptable in 10 of 20 patients (50%) in Gp I compared with 18 of 20 patients (90%) in Gp II (P < 0.05). MAP and HR decreased in both groups after induction of anaesthesia (P < 0.01). Both HR and MAP were significantly lower in Gp II compared with Gp I after tracheal intubation (P < 0.01). No patient in the present study developed bradycardia or hypotension. CONCLUSIONS: We conclude that remifentanil (3 microg.kg(-1)), administered before propofol (3 mg.kg(-1)) provides acceptable tracheal intubating conditions in children, and completely inhibited the increase in HR and MAP associated with intubation.     

Endoscopic resection of sinonasal malignancies: a preliminary report

BACKGROUND: A minimally invasive endoscopic approach for the management of sinonasal malignancy offers several advantages including excellent illumination, maximal preservation of uninvolved vital structures, and sparing of facial incisions. The purpose of this study was to evaluate the outcome and morbidity of endoscopic resection with or without combined radiotherapy and/or chemotherapy. METHODS: Forty-seven patients with sinonasal malignancy were diagnosed and/or treated with an endoscopic approach at The Cleveland Clinic Foundation and The University of Pennsylvania Medical Center from 1996 to 2003. Nineteen patients fulfilled the study criteria and had a minimally invasive endoscopic resection. Fifteen patients were treated with curative intent and four patients underwent palliative resection. RESULTS: The mean age was 56.9 (9-78 years) years and the mean follow-up period was 26.4 months. Combined radiation with or without chemotherapy pre- or postoperatively was given to 15 of 19 (78.9%) patients. Thirteen patients were resected strictly with an endoscopic approach and six patients were resected in combination with neurosurgery. There were no peri- and postoperative deaths. The local recurrence (LR) rate was 26.3% (5/19) and the distant metastasis rate was 15.8% (3/19). Overall survival rate (OS) was 78.9% (15/19) at a mean follow-up duration of 32.1 (4-74 months) months. The disease-free survival (DFS) rate was 68.4% (13/19) by clinical, endoscopic, and radiographic surveillance at a mean follow-up duration of 33.1 months. Patients treated with curative intent had LR, OS, and DFS rates of 21.4, 85.7, and 85.7%, respectively, and the patients treated for palliation had LR, OS, and DFS rates of 40, 60, and 15%, respectively. CONCLUSION: Minimally invasive endoscopic resection of sinonasal malignancy in combination with adjunctive therapies reduces treatment morbidity and yields LR, OS, and DFS rates that are comparable with traditional anterior craniofacial approaches.     

Inhibition of MUC4 expression suppresses pancreatic tumor cell growth and metastasis

The MUC4 mucin is a high molecular weight membrane-bound glycoprotein. It is aberrantly expressed in pancreatic tumors and tumor cell lines with no detectable expression in the normal pancreas. A progressive increase of MUC4 expression has also been observed in pancreatic intraepithelial neoplasia, suggesting its association with disease development. Here, we investigated the consequences of silencing MUC4 expression in an aggressive and highly metastatic pancreatic tumor cell line CD18/HPAF that expresses high levels of MUC4. The expression of MUC4 was down-regulated by the stable integration of a plasmid-construct expressing antisense-MUC4 RNA. A decrease in MUC4 expression, confirmed by Western blot and immunofluorescence analyses, resulted in diminished growth and clonogenic ability of antisense-MUC4-transfected (EIAS19) cells compared with parental, empty vector (ZEO) and sense transfected (ES6) control cells. In addition, EIAS19 cells displayed a significant decrease in tumor growth and metastatic properties when transplanted orthotopically into the immunodeficient mice. In vitro biological assays for motility, adhesion, and aggregation demonstrated a 3-fold decrease in motility of EIAS19 cells compared with control cells, whereas these cells adhered more and showed an increase in cellular aggregation. Interestingly, MUC4 down-regulation also correlated with the reduced expression of its putative interacting partner, HER2/neu, in antisense-MUC4-transfected cells. In conclusion, the present work demonstrates, for the first time, a direct association of the MUC4 mucin with the metastatic pancreatic cancer phenotype and provides experimental evidence for a functional role of MUC4 in altered growth and behavioral properties of the tumor cell.     

Fenretinide cytotoxicity for Ewing's sarcoma and primitive neuroectodermal tumor cell lines is decreased by hypoxia and synergistically enhanced by ceramide modulators

Patients with disseminated Ewing's family of tumors (ESFT) often experience drug-resistant relapse. We hypothesize that targeting minimal residual disease with the cytotoxic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR; fenretinide) may decrease relapse. We determined the following: (a) 4-HPR cytotoxicity against 12 ESFT cell lines in vitro; (b) whether 4-HPR increased ceramide species (saturated and desaturated ceramides); (c) whether physiological hypoxia (2% O(2)) affected cytotoxicity, mitochondrial membrane potential (DeltaPsi(m)) change, or ceramide species or reactive oxygen species levels; (d) whether cytotoxicity was enhanced by l-threo-dihydrosphingosine (safingol); (e) whether physiological hypoxia increased acid ceramidase (AC) expression; and (f) the effect of the AC inhibitor N-oleoyl-ethanolamine (NOE) on cytotoxicity and ceramide species. Ceramide species were quantified by thin-layer chromatography and scintillography. Cytotoxicity was measured by a fluorescence-based assay using digital imaging microscopy (DIMSCAN). Gene expression profiling was performed by oligonucleotide array analysis. We observed, in 12 cell lines tested in normoxia (20% O(2)), that the mean 4-HPR LC(99) (the drug concentration lethal to 99% of cells) = 6.1 +/- 5.4 microm (range, 1.7-21.8 microm); safingol (1-3 microm) synergistically increased 4-HPR cytotoxicity and reduced the mean 4-HPR LC(99) to 3.2 +/- 1.7 microm (range, 2.0-8.0 microm; combination index < 1). 4-HPR increased ceramide species in the three cell lines tested (up to 9-fold; P < 0.05). Hypoxia (2% O(2)) reduced ceramide species increase, DeltaPsi(m) loss, reactive oxygen species increase (P < 0.05), and 4-HPR cytotoxicity (P = 0.05; 4-HPR LC(99), 19.7 +/- 23.9 microm; range, 2.3-91.4). However, hypoxia affected 4-HPR + safingol cytotoxicity to a lesser extent (P = 0.04; 4-HPR LC(99), 4.9 +/- 2.3 microm; range, 2.0-8.2). Hypoxia increased AC RNA expression; the AC inhibitor NOE enhanced 4-HPR-induced ceramide species increase and cytotoxicity. The antioxidant N-acetyl-l-cysteine somewhat reduced 4-HPR cytotoxicity but did not affect ceramide species increase. We conclude the following: (a) 4-HPR was active against ESFT cell lines in vitro at concentrations achievable clinically, but activity was decreased in hypoxia; and (b) combining 4-HPR with ceramide modulators synergized 4-HPR cytotoxicity in normoxia and hypoxia.     

Pheochromocytoma associated with pregnancy

Pheochromocytoma associated with pregnancy is rare with potentially lethal consequences. Antepartum diagnosis improves the maternal and perinatal outcome. The issue of mode of delivery is unresolved. Its definitive treatment is surgical resection preceded by medical management. Surgical resection may be done during caesarean section as is reported in the present case.     

An unusual case of primary nasal tuberculosis with epistaxis and epilepsy

Primary nasal tuberculosis is rare. We report a case that was all the more extraordinary because of the age and sex of the patient (an 11-year-old boy), the unusual associated symptoms (epistaxis and grand and seizures), and the presence of intracranial extension. Clinical and radiologic findings on our initial evaluation suggested that the patient had a large sinonasal malignancy. The patient manifested no evidence of pulmonary tuberculosis. The diagnosis of primary nasal tuberculosis was established only after we obtained the results of histopathology of the excised mass and a subsequent tuberculin skin test; the diagnosis was confirmed by the patient's rapid response to antituberculosis drug therapy. We also review the relevant literature on this rare condition.     

Transformations in processing interaural time differences between the superior olivary complex and inferior colliculus: beyond the Jeffress model

Interaural time differences (ITDs) are used to localize sounds and improve signal detection in noise. Encoding ITDs in neurons depends on specialized mechanisms for comparing inputs from the two ears. Most studies have emphasized how the responses of ITD-sensitive neurons are consistent with the tenets of the Jeffress model. The Jeffress model uses neuronal coincidence detectors that compare inputs from both sides and delay lines so that different neurons achieve coincidence at different ITDs. Although Jeffress-type models are successful at predicting sensitivity to ITDs in humans, in many respects they are a limited representation of the responses seen in neurons. In the superior olivary complex (SOC), ITD-sensitive neurons are distributed across both the medial (MSO) and lateral (LSO) superior olives. Similar response types are found in neurons sensitive to ITDs in two signal types: low-frequency sounds and envelopes of high-frequency sounds. Excitatory-excitatory interactions in the MSO are associated with peak-type responses, and excitatory-inhibitory interactions in the LSO are associated with trough-type responses. There are also neurons with responses intermediate between peak- and trough-type. In the inferior colliculus (IC), the same basic types remain, presumably due to inputs arising from the MSO and LSO. Using recordings from the SOC and IC, we describe how the response types can be described within a continuum that extends to very large values of ITD, and compare the functional organization at the two levels.