This exercise is useful not only for young surgeons who wish to learn microsurgical techniques but also for more experienced surgeons who need to maintain or improve their skills.

The chorda tympani (CT) and glossopharyngeal (GL) nerves of several mammalian species respond differently to umami substances (US) such as monosodium glutamate (MSG), disodium 5'-inosinate (IMP) and disodium 5'-guanylate (GMP). In mice and rhesus monkeys, responses to US are greater in the GL than the CT nerve, with the GL nerve containing larger numbers of MSG-sensitive fibers. Gurmarin, a sweet response inhibitor, suppresses the mouse CT responses to the mixture of MSG and IMP to approximately 65% of control levels but not to the metabotropic and ionotropic glutamate agonists 2-amino-4-phophonobutyrate and N-methyl-D-aspartate. Gurmarin does not inhibit any taste responses in the GL. In mice, CT responses to MSG may be masked by their greater sensitivity to sodium ions. Calcium imaging studies demonstrate that some mouse taste cells isolated from the fungiform papilla innervated by the CT respond selectively (as indicated by a rise in intracellular Ca(2+) concentrations) to MSG and/or IMP or GMP. These MSG responses are not suppressed notably by reducing the Ca(2+) concentration of the stimulus solution, suggesting that the observed Ca(2+) release is from intracellular stores. Measurements of second messengers in the mouse fungiform papilla have revealed consistently that MSG elicits increases in both inositol 1,4,5-trisphosphate and adenosine 3', 5'-cyclic monophosphate levels. Together, these results suggest that US may stimulate two different transduction mechanisms in the fungiform papilla. They also suggest that gurmarin-insensitive components of receptors for US, including metabotropic and ionotropic glutamate receptors, may be commonly involved in transduction for umami taste in taste cells on both anterior and posterior parts of the tongue.

These studies tested the hypothesis that the cerebral vasospasm that follows subarachnoid hemorrhage (SAH) is due to alterations in endothelin (ET) and ET receptor expression. Eight monkeys underwent cerebral angiography and induction of SAH. Angiography was repeated 7 days later to confirm the presence of cerebral vasospasm, and animals were killed. RNA was isolated from right (vasospastic) and left (control) side middle cerebral arteries and surrounding cerebral cortex. The levels of prepro (PP) ET-1 (ppET-1) and ppET-3 and ETA and ETB receptor MRNAs were determined using a quantitative reverse transcriptase polymerase chain reaction-based assay. ET-1 peptide was also measured in CSF at baseline and after 7 days. Specific agonist binding to ETA and ETB receptors in both middle cerebral arteries and in surrounding brain cortex was measured in three animals by autoradiographic binding assays. Levels of ETB receptor mRNA were 3.4 +/- 2.2-fold higher in the right than in the left cerebral arteries (p < 0.01). There were no significant differences in the levels of ppET-1, ppET-3, or ETA receptor mRNA in cerebral arteries. ET-1 peptide was not elevated in CSF. Levels of ETA and ETB receptor mRNAs were 2.6 +/ 1.1- and 2.1 +/ 1.3-fold higher, respectively, in the right than in the left cerebral cortex, while the level of ppET-3 mRNA was 2.1 +/- 1.0-fold lower. There were no differences in ppET-1 mRNA levels between right and left cerebral cortex. Binding to ETA and ETB receptors in cerebral arteries and cortex did not differ significantly between right and left sides. These results do not support the hypothesis that overexpression of ET-1 is principal cause of vasospasm, but rather they suggest that SAH causes complex changes in the ET system that together are responsible for the cellular response to SAH.

Thirty-one monkeys were randomly divided into three groups to undergo baseline cerebral angiography followed by induction of subarachnoid hemorrhage by placement of autologous blood clot along the right-sided arteries of the anterior circle of Willis (Day 0). The monkeys were then given drug vehicle or one of two endothelin (ET) antagonists, BQ-123 (6 mg/kg/day) or bosentan (5 mg/kg/day) intracisternally. The BQ-123 was administered by continuous infusion from a subcutaneous pump and the bosentan was given by twice-daily injections into an Ommaya reservoir in the subcutaneous space with a catheter along the right middle cerebral artery (MCA). Seven days later (Day 7), angiography was repeated and the animals were killed. Comparison of arterial diameters shown on angiograms between Day 0 and Day 7 groups given placebo and bosentan showed significant reductions in the diameters of the right intradural internal carotid (28% +/- 6% and 30% +/- 6%, respectively, paired t-test, p < 0.05), anterior cerebral artery (29% +/- 8% and 32% +/- 6% respectively +/- 6%, respectively) and MCA (34% +/- 6% and 46% +/- 4%, respectively). Animals injected with BQ-123 had significant narrowing of the right extradural internal carotid artery (7% +/- 6%) and the basilar artery (11% +/- 3%), but not of the right MCA. Comparison of arterial diameters between groups at Day 7 showed significant variance in the right extradural internal carotid, both intradural internal carotid, right middle cerebral, and left anterior cerebral arteries; the animals injected with BQ-123 developed significantly less arterial narrowing these those receiving bosentan and placebo. Bosentan was not detected in the cerebrospinal fluid aspirated from the cisterna magna on Day 7, whereas BQ-123 was detected in two animals. We can infer from these results that BQ-123 prevents vasospasm following subarachnoid hemorrhage in monkeys, that further investigations of ET antagonists are warranted, and that ET may be an important pathophysiological mediator of vasospasm. The lack of efficacy of bosentan may be related to inadequate cerebrospinal fluid levels obtained by administration twice-daily through an Ommaya reservoir.

Abnormalities of coagulation and fibrinolysis in 12 head-injured patients were studied in early (within 24 hours of onset) and late (10th to 17th day after onset) stages. alpha 2 Plasmin inhibitor (alpha 2PI), antithrombin III (ATIII), and fibrinopeptide A (FPA) and B beta 15-42 (FPB beta) were measured in particular, in addition to the usual tests (platelet count (PLT), prothrombin time (PT), partial thromboplastin time, fibrinogen, and fibrin/fibrinogen degradation products (FDP)). alpha 2PI was abnormally lower, and FPA and FPB beta were much higher; fibrinogen and ATIII were moderately lower in the early stage than in the late stage in 6 head-injured patients with postoperative intracranial hemorrhage. alpha 2PI, ATIII, and fibrinogen were moderately lower and FPA was moderately higher in the early stage than in the late stage in 6 head-injured patients without postoperative intracranial hemorrhage. PLT and fibrinogen were lower, alpha 2PI was much lower, and FPA was much higher in the 6 patients with postoperative intracranial hemorrhage than in the 6 patients without postoperative intracranial hemorrhage. One patient with acute epidural and subdural hematomas had recurrent postoperative intracerebral hematoma twice. This recurrent hemorrhage was due to disseminated intravascular coagulation (DIC) caused by primary brain damage and was associated with extremely high FPA and FPB beta levels and abnormally low alpha 2PI and PLT. Fresh-frozen plasma and intravenous low-dose heparin were administered after the two recurrent hemorrhages, after which FPA and FPB beta normalized immediately, although other screening tests showed only gradual improvement.(ABSTRACT TRUNCATED AT 250 WORDS)