Primary malignant melanoma: a rare cause of mediastinal mass

A case of primary malignant melanoma in the mediastinum presenting as recurrent laryngeal nerve palsy is reported. Tissue biopsy at mediastinotomy yielded a diagnosis of malignant melanoma. The mass was fixed to the left aspect of the trachea and to the upper border of the left main bronchus and could not be removed surgically. Further extensive clinical and radiological investigations revealed no evidence of tumor elsewhere in the body.     

Voltage Oscillations in Xenopus Spinal Cord Neurons: Developmental Onset and Dependence on Co-activation of NMDA and 5HT Receptors

The development of intrinsic, N-methyl-D-aspartate (NMDA) receptor-mediated voltage oscillations and their dependence on co-activation of 5-hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis. Under tetrodotoxin, 100 μM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2–5 μM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co-activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D-2-amino-5-phosphonovaleric acid (APV) or by excluding Mg²⁺ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non-selective 5HT_1a receptor agonist, 5-carboxamidotryptamine (5CT) and both 5HT- and 5CT-induced oscillations were abolished by pindobind-5HT₁, a selective 5HT_1a receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage-dependent block of NMDA channels by Mg²⁺, membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4–8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an ‘apparent’ decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg²⁺ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage-dependent Mg²⁺ block. When the membrane potential was depolarized by ～20 mV via depolarizing current injection (to mimic the NMDA-induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg²⁺ saline. The results suggest that intrinsic, NMDA receptor-mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co-activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage-dependent block of the NMDA ionophore by Mg²⁺ through activation of receptors with 5HT_1a-like pharmacology.     

Diagnostic accuracy of progressive supranuclear palsy in the Society for Progressive Supranuclear Palsy brain bank.

Diagnostic accuracy has been addressed previously for Parkinson's disease in a brain bank collection, but accuracy of progressive supranuclear palsy (PSP) has not been addressed in a similar setting. Clinical and genetic features of pathologically confirmed cases of PSP were compared with misdiagnosed cases to determine ways to improve diagnostic accuracy. Medical records were reviewed for 180 cases sent to the Society of Progressive Supranuclear Palsy Brain Bank that had standardized neuropathologic evaluations as well as determination of apolipoprotein E and tau genotypes. Of the 180 cases studied, 137 had PSP and 43 had other pathologic diagnoses. Corticobasal degeneration (CBD), multiple system atrophy (MSA), and diffuse Lewy body disease (DLBD) accounted for 70% of the misdiagnosed cases. History of tremor, psychosis, dementia, and asymmetric findings were more frequent in misdiagnosed cases. The frequency of H1 tau haplotype (93 vs. 80%) and H1H1 genotype (86 vs. 66%) were significantly greater and APOE epsilon4 carrier state was significantly less (17 vs. 41 %) in PSP compared with misdiagnosed cases. Pathologic evaluation of clinically diagnosed PSP remains important for definitive diagnosis, and CBD, MSA, and DLBD are the disorders most likely to be misdiagnosed as PSP. Tremor, psychosis, early dementia, asymmetric findings, absence of H1 haplotype, and presence of APOE epsilon4 should raise questions about a diagnosis of PSP.     

Dual Effects of Hexanol and Halothane on the Regulation of Calcium Sensitivity in Airway Smooth Muscle

Background: Contraction of airway smooth muscle is regulated by receptor-coupled mechanisms that control the force developed for a given cytosolic calcium concentration (i.e., calcium sensitivity). Halothane antagonizes acetylcholine-induced increases in calcium sensitivity by inhibiting GTP-binding (G)-protein pathways. The authors tested the hypothesis that hexanol, like halothane, inhibits agonist-induced increases in calcium sensitivity in airway smooth muscle by inhibiting G-protein pathways.

Methods: Calcium sensitivity was assessed using [alpha]-toxin-permeabilized canine tracheal smooth muscle. In selected experiments, regulatory myosin light chain phosphorylation was also determined by Western blotting in the presence and absence of 10 mm hexanol and/or 100 [mu]m acetylcholine.

Results: Hexanol (10 mm) and halothane (0.76 mm) attenuated acetylcholine-induced calcium sensitization by decreasing regulatory myosin light chain phosphorylation during receptor stimulation. Hexanol also inhibited increases in calcium sensitivity due to direct stimulation of heterotrimeric G-proteins with tetrafluoroaluminate but not with 3 [mu]m GTP[gamma]S, consistent with prior results obtained with halothane. In contrast, in the absence of receptor stimulation, both compounds produced a small increase in calcium sensitivity by a G-protein-mediated increase in regulatory myosin light chain phosphorylation that was not affected by pertussis toxin treatment.     

Duration of action of antispasmodic agents: novel use of a mouse model as an in vivo pharmacological assay.

OBJECTIVE: Radial arteries are increasingly used as conduits for coronary artery bypass grafts, but perioperative graft vasospasm remains a concern. In vitro testing has demonstrated the efficacy of phenoxybenzamine and verapamil/nitroglycerin as topical antispasmodic agents, but their duration of action in vivo is unknown. Using an in vivo mouse model, we measured their duration of action in functioning vascular grafts, and compared this to their in vitro duration of action in ungrafted vascular segments. METHODS: Two millimetre mouse aortic segments (C57/BL6) were incubated with phenoxybenzamine, verapamil/nitroglycerin, or buffer (controls) for 15 min in organ chambers. Isometric tension responses to phenylephrine and prostaglandin F2alpha were measured at 0, 2, 6 and 12 h post-incubation. In parallel, 36 murine infrarenal aortic interposition grafts (2 mm) were performed. Twelve grafts were pre-treated (15 min) with phenoxybenzamine, 12 with verapamil/nitroglycerin and 12 remained untreated (controls). Isometric tension responses to the same agonists were measured in grafts harvested 2, 6, 13 and 23 h after surgery. RESULTS: Phenoxybenzamine prevented alpha-adrenergic vasoconstriction for up to 16 h in vivo (grafts), and 12h in vitro (ungrafted segments). Verapamil/nitroglycerin was effective for at least 2 h in vitro, but did not prevent vasoconstriction after 2 h in vivo. CONCLUSIONS: The mouse model appears to be a useful technique for assessing the pharmacological properties of antispasmodic agents in vivo. Phenoxybenzamine has an extended action in arterial grafts in vivo. Verapamil/nitroglycerin is short-lived in vivo but lasts longer in vitro. Measurements of antispasmodic duration of action in vitro should be interpreted with caution.     

An assessment of the characteristics of n-type diodes for use in electron beam radiotherapy.

Diodes are now commercially available for use in electron beams. This paper aims to assess their response and limitations under different clinical conditions. Parameters considered were applicator factors, focus skin distance (FSD), angle of incidence, and temperature dependence. The beam perturbation was also measured. The beam energies used varied from 5 to 17 MeV. Applicator factors, measured at the surface of a phantom, differed by up to 7% compared with ion chamber measurements at Dmax. Similarly, large differences were found in FSD dependence. The temperature dependence was found to be approximately double the manufacturer's specification at 0.7% per degree Centigrade and the angular dependence was within the specification of +/- 2% for angles of +/- 30 degrees. The beam perturbation was measured as a maximum of 25% for 5-MeV electrons. The measurements were compared to other published data but this is highly dependent on the methodology employed. It was concluded that the diodes could be used in some circumstances, but only if used with extreme caution. An extensive set of commissioning measurements would be required before introducing the diodes into use clinically.     

Comparison between two valsalva techniques for improvement of hypopharyngeal nasendoscopy: a preliminary communication

Objective: To compare the nasal valsalva with the trumpet manoeuvre and anterior neck skin traction as aids to nasendoscopic examination of the hypopharynx. Design: Randomised, controlled comparison of examination techniques. Setting: Single tertiary referral centre. Participants: Twenty‐six adult patients requiring hypopharyngeal nasendoscopic examination were recruited. Patients were examined with both techniques in a randomised order that was recorded to video cassette. Main Outcome Measures: Blinded assessment of the percentage visualisation of the pyriform fossae, post‐cricoid and upper oesophageal sphincter was carried out by three consultant otolaryngologists independently. Results: Mean percentage scores (and 95% confidence intervals) for nasal valsalva versus trumpet manoeuvre for the three consultants, respectively, were as follows: right pyriform fossa: 77(68, 87) versus 80(71, 91), 61(55, 66) versus 60(54, 66), 46(38, 54) versus 45(37, 54); left pyriform fossa: 76(65, 87) versus 80(69, 91), 59(53, 64) versus 55(49, 61), 42(35, 49) versus 42(35, 50); post‐cricoid: 55(44, 67) versus 59(47, 71), 53(46, 60) versus 53(46, 60), 32(25, 39) versus 32(25, 39); upper oesophageal sphincter: 11(1, 21) versus 21(11, 31), 15(9, 21) versus 20(14, 26), 4(0, 8) versus 7(3, 11). No significant difference was found between the two techniques at any subsite. Individual differences were noted in a minority of patients where one or other technique gave a clearly improved view. Conclusions: The nasal valsalva and the trumpet manoeuvre with anterior neck skin traction are complementary techniques for improving the view of the hypopharynx.     

Features of pediatric head injury in Hong Kong

Head injury in children causes special concern in most communities. From 1989 to 1994, 2,785 children younger than 16 years old were admitted to our neurosurgical service because of head injury. Fall from a height was the major cause of head injury leading to admission in infants and children in preschool age groups, whereas traffic-related or bicycle-related accidents were more likely to be the cause of head injury for those aged 11–15 years. In all age groups there was a male preponderance. The overall mortality was 0.6%. Traffic-ralated accidents caused more severe injury and accounted for 67% of all fatalities. For patients under 6 years old, about 40% of head injuries occurred at home. Preventive measures for pediatric head injury in Hong Kong are suggested.     

Memory following cholinergic (NBM) and noradrenergic (DNAB) lesions made singly or in combination: potentiation of disruption by scopolamine

Groups of rats were trained on either delayed matching or nonmatching to position tasks, then divided into four subgroups and given the following bilateral lesions: (a) SHAM [vehicle injection into the nucleus basalis magnocellularis (NBM) and dorsal noradrenergic bundle (DNAB)], (b) DNAB (6-hydroxydopamine lesion of the DNAB, vehicle into the NBM), (c) NBM (quisqualic acid lesion of the NBM, vehicle into the DNAB) and (d) DUAL (neurotoxin lesions of both DNAB and NBM). Following postoperative recovery, the DUAL lesion subjects were slightly impaired, but by the seventh day of testing all groups were performing at similar levels. This strongly suggests that quisqualate lesions of the NBM are not sufficient to produce severe and lasting mnemonic disorders resembling those seen in Alzheimer's disease (AD). These data also indicate that the noradrenergic system may not be of critical importance with respect to cognition. It was reasoned that an additional anticholinergic treatment might exacerbate an underlying deficiency. All groups were injected, peripherally, with the cholinergic antagonist scopolamine (0-0.5 mg/kg). This drug dose-dependently disrupted performance in all groups. Moreover, the highest dose had a marked effect in the DUAL group, impairing performance even when no mnemonic burden was present (at zero delay). The results suggest that cholinergic NBM and noradrenergic DNAB lesions produce only transient mnemonic deficiencies. A combination of the two can be disruptive, but longer term task (or reference) memory is the primary process affected, and only under certain conditions. The implication of these findings to research concerning animal models relating to Alzheimer's disease is discussed.