Folate and vitamin B-6 status are not associated with homocysteine, oxidative stress and antioxidant capacities in patients with hepatocellular carcinoma.

The purpose of this study was to study the effects of serum folate and plasma pyridoxal 5'-phosphate (PLP) on plasma homocysteine, oxidative stress and antioxidant capacities in 44 hepatocellular carcinoma (HCC) patients and 56 healthy controls. The responses of folate, vitamin B-6, homocysteine, oxidative stress and antioxidant enzyme activities in HCC patients before and after tumor resection were also determined. Patients with HCC before tumor resection had significantly lower folate, PLP, homocysteine, glutathione peroxidase and superoxide dismutase levels, but higher malondialdehyde, total antioxidant capacity and glutathione S-transferase activity when compared with healthy controls. Oxidative stress was significantly decreased to a level similar to that of healthy controls after tumor resection in the HCC group. There were no associations of folate and PLP with plasma homocysteine, indicators of oxidative stress and antioxidant capacities. Serum folate and plasma PLP were not significant factors affecting plasma homocysteine, oxidative stress and antioxidant capacities in patients with HCC.

Transcranial magnetic brain stimulation modulates blepharospasm: a randomized controlled study.

BACKGROUND: Benign essential blepharospasm (BEB) is a common form of focal dystonia. Besides pathology in the basal ganglia, accumulating evidence suggests pathologic changes in the anterior cingulate cortex (ACC). METHODS: This is a randomized, sham-controlled, observer-blinded prospective study. In 12 patients with BEB, we evaluated the effects of a 15-minute session of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the ACC with stimulation intensities at 100% active motor threshold with 3 stimulation coils: a conventional circular coil (C-coil), a sham coil (S-coil), and a Hesed coil (H-coil, which allows stimulation of deeper brain regions. Primary outcome was the clinical effects on BEB (blink rate, number of spasms rated by a blinded physician and patient rating before, immediately after, and 1 hour after stimulation); secondary outcome was the blink reflex recovery curve. RESULTS: Subjective stimulation comfort was similar for each coil with no stimulation-associated adverse events. Stimulation with the H- and C-coils resulted in a significant improvement in all 3 outcome measures and was still detectable in physician rating and patient rating 1 hour after stimulation. S-coil stimulation had no effects. The active motor threshold was significantly lower for the H-coil compared to the other 2 coils. CONCLUSIONS: rTMS could be used as a therapeutic tool in BEB. Further studies will be necessary to show whether repeated stimulation applications result in lasting clinical effects. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with BEB, H- and C-coil rTMS is safe and improves clinical symptoms of BEB immediately and 1 hour after stimulation.

Blepharospasm and the modulation of cortical excitability in primary and secondary motor areas.

BACKGROUND: Traditionally, benign essential blepharospasm (BEB) is considered a disorder caused by basal ganglia dysfunction. Electrophysiologic and brain imaging studies suggest pathologic changes in excitability in the primary motor cortex (MC), anterior cingulate (AC), and secondary motor areas, such as premotor (PMC) and supplementary motor cortices (SMA). METHODS: In this pilot study of 7 patients with BEB, we experimentally reduced cortical excitability of 4 areas: MC (first dorsal interosseus area), PMC, SMA, and AC, each with 3 noninvasive techniques: low-frequency repetitive transcranial magnetic stimulation (lfrTMS), continuous theta burst stimulation (cTBS), and cathodal transcranial direct current stimulation (tDCS). Primary outcome was the clinical effects on blepharospasm (blink rate observation by an investigator blinded to the intervention and subjective rating by the patient); secondary outcome was the blink reflex recovery curve (BRR). RESULTS: lfrTMS resulted in a significant improvement over all 4 brain areas for physician rating, patient rating, and BRR, whereas cTBS and tDCS showed only trends for improvement in physician rating, but no improvements for patient rating and BRR. lfrTMS had a significantly higher effect over AC than MC for physician rating, but no differences were seen for other pairwise comparisons of stimulated brain areas. CONCLUSIONS: Electrophysiologic and clinical improvements by functional inhibition of the medial frontal areas using low-frequency repetitive transcranial magnetic stimulation suggests that hypersensitivity of the anterior cingulate is directly or indirectly involved in the pathophysiology of benign essential blepharospasm. Inhibition of these areas using low-frequency repetitive transcranial magnetic stimulation could provide a therapeutic tool and is worthy of a larger study.

Bilateral isolated phrenic neuropathy causing painless bilateral diaphragmatic paralysis.

The authors report four patients with a syndrome of painless bilateral isolated phrenic neuropathy. Electrophysiologic testing demonstrated active denervation restricted to the diaphragm. Long-term recovery was poor. The authors conclude that bilateral isolated phrenic neuropathy is a cause of painless diaphragmatic paralysis distinguishable from immune brachial plexus neuropathy and other neuromuscular disorders with similar clinical presentation.

Lack of evidence of association of p21WAF1/CIP1 polymorphism with lung cancer susceptibility and prognosis in Taiwan.

An association between the Arg allele of the p21WAF1/CIP1 codon 31 polymorphism and lung cancer has been reported. However, the genotype distribution of the p21 codon 31 polymorphism, as well as the association of this polymorphism with lung cancer risk and prognosis, remain undefined in the Taiwanese population. Therefore, we investigated the genotype distribution of the p21 codon 31 polymorphism in 155 lung cancer patients and 189 non-cancer controls. The genotype frequencies in the Taiwanese non-cancer controls were 0.51 (Ser) and 0.49 (Arg). Chi2 analysis indicated significant differences in Taiwanese genotype distribution of p21 from those reported for Swedes (P=0.001), Caucasians (P=0.001), Indians (P=0.001), and African-Americans (P=0.001). However, our data did not demonstrate an association of the Arg allele of the p21 polymorphism with lung cancer risk in Taiwan. Lung cancer patients with Ser/Arg and Arg/Arg genotypes were at a nonsignificant 1.15-fold increased risk of lung cancer when compared to individuals with the Ser/Ser genotype (95%CI, 0.70-1.86). In addition, although p21 is a downstream target of p53, we found no significant correlation of the p21 polymorphism with the p53 polymorphism and p53 gene mutation in lung cancer patients. We further investigated the association of the p21 polymorphism with prognosis in 154 lung cancer patients. Patients with the Ser/Ser genotype tended to have a poorer prognosis than those with the Ser/Arg and Arg/Arg genotypes (P=0.097, by the log rank test). Our data suggest that the p21 codon 31 polymorphism may not play a significant role in cancer susceptibility and the prognosis of lung cancer patients in Taiwan.

DCAMKL1 encodes a protein kinase with homology to doublecortin that regulates microtubule polymerization.

Doublecortin (DCX) is a microtubule-associated protein required for neuronal migration to the cerebral cortex. DCAMKL1 consists of an N terminus that is 65% similar to DCX throughout the entire length of DCX, but also contains an additional 360 amino acid C-terminal domain encoding a putative Ca(2+)/calmodulin-dependent protein kinase. The homology to DCX suggested that DCAMKL1 may regulate microtubules, as well as mediate a phosphorylation-dependent signal transduction pathway. Here we show that DCAMKL1 is expressed throughout the CNS and PNS in migrating neuronal populations and overlaps in its expression with DCX and microtubules. Purified DCAMKL1 associates with microtubules and stimulates polymerization of purified tubulin and the formation of aster-like microtubule structures. Overexpressed DCAMKL1 leads to striking microtubule bundling in cell lines and cultured primary neural cells. Time-lapse imaging of cells transfected with a DCAMKL1-green fluorescent protein fusion protein shows that the microtubules associated with the protein remain dynamic. DCAMKL1 also encodes a functional kinase capable of phosphorylating myelin basic protein and itself. However, elimination of the kinase activity of DCAMKL1 has no detectable effect on its microtubule polymerization activity. Because DCAMKL1 is coexpressed with DCX, the two proteins form a potentially mutually regulatory network linking calcium signaling and microtubule dynamics.

Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons.

Doublecortin (DCX) is required for normal migration of neurons into the cerebral cortex, since mutations in the human gene cause a disruption of cortical neuronal migration. To date, little is known about the distribution of DCX protein or its function. Here, we demonstrate that DCX is expressed in migrating neurons throughout the central and peripheral nervous system during embryonic and postnatal development. DCX protein localization overlaps with microtubules in cultured primary cortical neurons, and this overlapping expression is disrupted by microtubule depolymerization. DCX coassembles with brain microtubules, and recombinant DCX stimulates the polymerization of purified tubulin. Finally, overexpression of DCX in heterologous cells leads to a dramatic microtubule phenotype that is resistant to depolymerization. Therefore, DCX likely directs neuronal migration by regulating the organization and stability of microtubules.

Urgent adenotonsillectomy for upper airway obstruction.

Adenotonsillar hypertrophy has been documented to cause chronic upper airway obstruction resulting in cardiopulmonary sequelae in children. It has been less recognized that long-term adenotonsillar hypertrophy may additionally cause acute, life-threatening airway obstruction. A review of 5000 adenotonsillectomies performed at 3 New York Medical College affiliated hospitals from 1982 to 1989 showed 6 pediatric patients with progressive upper airway obstruction severe enough to necessitate intubation in the emergency room or operating room, and subsequent urgent adenotonsillectomy after cardiorespiratory stabilization. Patients were monitored in the ICU with pre- and postoperative blood gases. Observations of cyanosis, cor pulmonale, and use of accessory respiratory muscles were carefully recorded. This study illustrates that life-threatening upper airway obstruction may be due to chronic adenotonsillar enlargement and require treatment by urgent adenotonsillectomy.

An anatomic study of the external laryngeal framework with surgical implications.

Precise knowledge of the level of the vocal fold as projected on the external thyroid cartilage is of critical importance for the performance of thyroplasty type I and supraglottic laryngectomy. Measurements of the external laryngeal framework were made on the larynges of 18 human cadavers in order to identify landmarks that will aid the surgeon in determining endolaryngeal anatomy. On the basis of our results, the following guidelines are recommended: (1) Thyroid cartilage incision for supraglottic laryngectomy should be made on a line joining the juncture of the upper one third and lower two thirds of the midline length and the juncture of the upper one third and lower two thirds of the oblique line. This will ensure a position above the level of the anterior commissure and the true vocal cord; (2) In thyroplasty type I, the superior border of the thyroid cartilage window should be made at a line joining the midpoint of the midline length and the juncture of the upper two thirds and lower one third of the oblique line. Formation of the cartilage window according to this guideline will ensure its placement lateral to the vocalis muscle.

Management of odontogenic sinusitis with persistent oro-antral fistula.

Sixteen patients were treated for odontogenic sinusitis secondary to persistent oro-antral fistula. Males outnumbered females 12 to 4. Frequency of presentation increased directly with age. Chronic signs and symptoms included facial pain, swelling, tenderness and nasal and oral discharge. The clinical diagnosis of chronic sinusitis was confirmed in all cases by radiographic findings. An opacified maxillary sinus with or without ethmoid involvement was observed in all 16 patients. Surgical pathology revealed chronic mucosal thickening and/or antral polyps in 69% of the cases. Surgical treatment of the sinusitis consisted of antrostomy alone or in combination with Caldwell-Luc procedure. The oro-antral fistula was repaired with mucosal flaps from the buccal and/or palatal region. No postoperative recurrences have been noted during a follow-up period of six months to seven years. Bacterial cultures grew out pure aerobes (44%) or mixed aerobic-anaerobic bacteria (44%). None yielded pure anaerobes. The bacteriologic spectrum was notably lacking in S. pneumoniae and H. influenzae and differed from organisms commonly found in sinusitis of rhinogenous origin.

Cystic parotid masses in HIV infection.

Cystic enlargement of the parotid gland is a newly described manifestation of infection with human immunodeficiency virus (HIV). A review of 15 such patients with respect to clinical presentation, natural history, and management is presented. Follow-up ranges from 1 to 27 months, averaging 10 months. In 47% of the patients, parotid swelling was the chief complaint leading to the diagnosis of HIV infection. T-cell analysis revealed the tendency for this lesion to occur in the early stages of immunodeficiency when T-cell counts are high. Histologic examination revealed findings resembling benign lymphoepithelial lesion. It is felt that these lesions are a local manifestation of a systemic disease and treatment should be tailored with this in mind. Surgical excision may not be necessary. Fine-needle aspiration (FNA) was found to be useful diagnostically and therapeutically. Recognition of this entity is essential for the head and neck specialist in providing an early diagnosis of HIV infection.

Parotid disease associated with human immunodeficiency virus infection.

Cystic parotid enlargement is a newly recognized manifestation of HIV infection. It commonly occurs early in the spectrum of HIV-related illnesses and may be part of LAS. Serologic confirmation of HIV infection and CT imaging usually establishes the diagnosis. Cytologic or histopathologic evaluation may be required for diagnostic confirmation and for management.

Effects of lateral manual compression upon glottic incompetence: objective evaluations.

Forceful manual compression of the thyroid and cricoid cartilages modifies the position, shape, and tension of the vocal folds. This is the basis of the four laryngeal manual compression tests, adjunctive examinations used as a means of preoperative assessment of patients for medialization laryngoplasty, ie, Isshiki thyroplasty types I and IV and arytenoid adduction. The laryngeal manual compression tests are simple to perform and noninvasive. Each of the four examinations yields valuable information on the effects on the voice of changes in vocal cord characteristics produced by manual compression. In this report, one of the four tests, lateral manual compression, is evaluated objectively with well-attested methods of videostroboscopic, aerodynamic, and acoustic analysis. The technique of performing lateral manual compression is described, and advantages and disadvantages are noted and compared in 10 patients. Preliminary findings in 4 patients in this group indicate that medialization laryngoplasty should be considered when test results are conclusive of effective glottic closure. Data derived in this preliminary study will be augmented as patients are added to the series.

Benign nasopharyngeal masses and human immunodeficiency virus infection.

Manifestations of the acquired immunodeficiency syndrome are common in the head and neck and are becoming well known to the otolaryngologist. We present a series of seven patients who complained of nasal obstruction and hearing loss and were found, on examination, to have large obstructing nasopharyngeal masses and otitis media with effusion. Biopsy revealed benign lymphoid proliferation. Because of a suspicion of human immunodeficiency virus infection by history, antibody titers were obtained and were found to be positive in all cases. With the known increased rate of aggressive extranodal B-cell lymphomas in human immunodeficiency virus-infected patients, its existence in the nasopharynx should be ruled out histologically in symptomatic patients. Nasal obstruction and hearing loss secondary to nasopharyngeal lymphoid proliferation in high-risk patients can be an early sign of human immunodeficiency virus infection. Patients presenting with this clinical entity should be advised to have serologic testing and further treatment and counseling if necessary.

Osteoma of the tongue.

Osteomas are benign bony neoplasms commonly found in long bones and in the skull and facial bones. Osseous growths within soft tissue structures of the head and neck are rare. Review of the English literature reveals only 31 cases of osteomas within the soft tissues of the tongue and 2 in the buccal mucosa. We report on a patient with a bony hard asymptomatic mass at the base of the tongue, which was found to be an osteoma by biopsy. Complete removal was declined by the patient. There was no progression during a six-month period of follow-up.

Paranasal sinus disease with intracranial extension: aspergillosis versus malignancy.

Aspergillus is a fungus with world-wide distribution and a common endogenous contaminate of the upper respiratory tract. It has become an increasingly recognized pathogen in the paranasal sinuses. In its pathologic state it presents in one of several forms that may represent a continuum of the disease: allergic, noninvasive, invasive, and fulminant. The progression and prognosis of these disease depends on the location and immunologic status of the patient. This case represents the fourth reported case of a nonimmunologic compromised patient with intracranial extension of aspergillosis. The patient presented with unilateral pansinusitis and radiographic evidence of orbital and anterior cranial fossa invasion. This case illustrates the difficulty of establishing the diagnosis of invasive aspergillosis and differentiating it from neoplastic entities. Radiographs and photomicrographs will be presented to establish this premise.

Risk factors for intubation injury of the larynx.

The endolaryngeal structures are subjected to insult from prolonged endotracheal intubation. Factors that may exacerbate this injury include intubation technique, duration of intubation, tube geometry and constitution, frequency of reintubation, and patient-related factors such as concomitant medical diseases. The contribution of underlying medical disease to laryngeal intubation injury was studied prospectively by sequential endoscopy from the time of tracheotomy. Diabetes mellitus, congestive heart failure, and a history of stroke or tuberculosis increased the likelihood of severe laryngeal injury. The association of these disorders with severe laryngeal injury should lead to consideration of earlier tracheotomy in such patients.