Cerebrovascular reserve capacity in ischemia due to occlusion of a major arterial trunk: studies by Xe-CT and the acetazolamide test.

Classifications based on clinical and radiographic criteria have proved to be inadequate predictors of the course of cerebral ischemia or its response to therapy. In this study the cerebrovascular reserve capacity (CRC) of 46 patients with symptomatic cerebrovascular ischemia was studied by stable xenon-enhanced CT (Xe-CT) combined with the acetazolamide test. Fifteen patients had internal carotid artery (ICA) occlusion, 10 had ICA stenosis, 10 had middle cerebral artery (MCA) occlusion, and 11 had MCA stenosis. In the patients with chronic cerebral ischemia due to occlusive lesions of the ICA and MCA, the CRC was reduced most in those with MCA occlusion, followed, in descending order, by those with ICA stenosis, MCA stenosis, and ICA occlusion. Our results indicate that measurement of the CRC elucidates cerebral hemodynamic factors that cannot be detected by angiography in patients with chronic cerebral ischemia and that Xe-CT combined with the acetazolamide test is useful for this purpose.     

Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left ventricle

Caffeine causes a considerable O(2) waste for positive inotropism in myocardium by complex pharmacological mechanisms. However, no quantitative study has yet characterized the mechanoenergetics of caffeine, particularly its O(2) cost of contractility in the E(max)-PVA-VO(2) framework. Here, E(max) is an index of ventricular contractility, PVA is a measure of total mechanical energy generated by ventricular contraction, and VO(2) is O(2) consumption of ventricular contraction. The E(max)-PVA-VO(2) framework proved to be powerful in cardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) E(max) and VO(2) for excitation-contraction (E-C) coupling in the excised cross-circulated canine heart. We enhanced LV E(max) by intracoronary infusion of caffeine after beta-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO(2) and PVA with E(max) as a parameter. We then calculated the VO(2) for the E-C coupling by subtracting VO(2) under KCl arrest from the PVA-independent (or zero-PVA) VO(2) and the O(2) cost of E(max) as the slope of the E-C coupling VO(2)-E(max) relation. We found that this cost was 40% greater on average for caffeine than for calcium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O(2) wasting effect of the complex inotropic mechanisms of intracoronary caffeine at concentrations lower than 1 mmol/l in a beating whole heart.     

Elective neck clipping for unruptured aneurysms in elderly patients

BACKGROUND: With the recent advancements of neuroimaging techniques, the number of unruptured aneurysms diagnosed in elderly patients has increased. However, the surgical indications in this special subgroup have not been studied critically. The purposes of this study were to analyze the results of elective neck clipping surgery for unruptured aneurysms in the elderly and to elucidate the surgical indications. METHODS: From 1985 to 1997, 96 patients, aged 70 years or older, with 103 unruptured cerebral aneurysms underwent elective neck clipping. There were 67 females and 29 males. Their ages ranged from 70 to 86, with a mean of 73.3 years. Seventy-five aneurysms were asymptomatic and 28 were symptomatic. The aneurysms were located on the internal carotid artery (46.6%), middle cerebral artery (35.9%), anterior cerebral artery (16.5%), and basilar artery (1.0%). RESULTS: The surgical outcome was a good recovery in 75 patients (78.1%), mild deficits in 12 (12.5%), severe deficits in 4 (4.2%), and death in 5 (5.2%). Recovery from preoperative symptoms with improved quality of life was seen in 22 (78.6%) of the 28 symptomatic cases. Multiple regression analysis showed that increase in the size of aneurysms and location on the middle cerebral artery and internal carotid artery were significantly related to a poor outcome. The causes of the five deaths were hemorrhagic infarction, systemic infection, and myocardial infarction. CONCLUSION: Surgery for elective neck clipping of unruptured aneurysms in the elderly should be considered in symptomatic patients with simple aneurysms that can be clipped without the use of temporary clips.     

The significance of arytenoid edema following radiotherapy of laryngeal carcinoma with respect to residual and recurrent tumour

We sometimes experience patients with persistent or progressive arytenoid edema, among which residual or recurrent cancer is often accompanied. Because it is difficult to distinguish tumour rest or recurrence from normal tissue sequelae in the early period after irradiation, it is important to know both the contributing factors for arytenoid edema, and the incidence of residual or recurrent tumours in patients with postirradiation laryngeal edema. We therefore reviewed the charts of 67 patients with early laryngeal carcinoma who had received a curative dose of irradiation in the last 5 years. Fourteen patients (20.9%) had moderate or severe laryngeal edema persisting for or developing at more than 3 months after completion of a course of definitive radiotherapy. The incidence was highest in supraglottic T₂ disease, followed by glottic T₂ tumour. Of the 14 patients with edema, six (42.9%) had persistent or recurrent disease. The primary disease was uncontrolled in 18 patients, 17 of whom received successful salvage surgery. In patients without residual tumours, the edema was usually moderate and resolved within a year, although four patients had chronic edema lasting more than a year after treatment. All four had supraglottic T₂ lesions and received 70 Gy of X-ray. We also reviewed, for sake of comparison, the records of 38 patients treated with radiotherapy at doses of more than 40 Gy between l975 and 1980, when endoscopic microsurgery for laryngeal cancer was introduced as a primary part of treatment. The incidence of persistent or late developed edema over the period, though not significant, was 36.8%: nearly twice that of the last 5 years. Microscopic endolaryngeal surgical procedures seem to have been a causal factor for edema in this period.     

Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with dobutamine.

BACKGROUND. We hypothesized that the effect of pimobendan (UD-CG 115 BS) to increase calcium sensitivity of contractile protein might result in less myocardial oxygen consumption (VO2) in comparison with dobutamine when they enhance ventricular contractility to the same extent. To examine this hypothesis, we compared the effects of pimobendan and dobutamine on left ventricular contractility and energetics using the frameworks of Emax (contractility index) and the relation between VO2 and PVA (systolic pressure-volume area, a measure of left ventricular total mechanical energy). METHODS AND RESULTS. We measured VO2, Emax, PVA, and force-time integral (FTI) in excised, cross-circulated, nonfailing dog hearts. The slope of the VO2-PVA relation reciprocally indicates the efficiency from PVA-dependent VO2 to the total mechanical energy (contractile efficiency). The VO2 intercept of the VO2-PVA relation, i.e., PVA-independent VO2, reflects energy utilization for excitation-contraction coupling. The ratio of FTI to PVA-dependent VO2 can be called contractile economy. Both drugs comparably enhanced Emax. Although the contractile economy was greater by 14 +/- 19% (p less than 0.05) for pimobendan than for dobutamine, the contractile efficiency was similar between the two drugs. Oxygen cost of contractility, defined as the slope of the relation between the PVA-independent VO2 and Emax, was the same between the two drugs. Other mechanoenergetic effects of both drugs were similar except for a greater coronary vasodilating effect of pimobendan. CONCLUSIONS. Pimobendan has almost the same mechanoenergetic effects as dobutamine but slightly greater contractile economy and coronary vasodilation. The calcium-sensitizing effect of pimobendan did not save the oxygen cost of contractility.     

Improved Quality of Life and Unchanged Magnetic Resonance Brain Imaging After Living Donor Liver Transplantation for Late-Onset Ornithine Transcarbamylase Deficiency: Report of a Case

We report the case of a 7-year-old girl with ornithine transcarbamylase deficiency whose quality of life (QOL) improved greatly after a living donor liver transplantation (LDLT). Ornithine transcarbamylase deficiency had been diagnosed when she was 2 years old and she finally underwent LDLT, with her father as the donor, when she was 7 years old. The patient had suffered episodes of hyperammonemic encephalopathy ranging from lethargy to coma, treated by hemodialysis twice before LDLT, and her intelligence quotient was borderline for her age. Preoperative magnetic resonance imaging (MRI) showed an atrophic area in the subcortical white matter of the frontal lobe. After LDLT, the patient suffered acute rejection with hyperamylasemia, but not hyperammonemia. Postoperative MRI and quantitative MR spectroscopy showed no changes in the subcortical lesion. She has been followed up carefully for 16 months and has had no further complications or any sign of hyperammonemia.     

Expression of endocrine-paracrine cells in prostatic carcinoma

Endocrine-Paracrine cells (EP cells) in prostatic carcinomas were screened by immunohistochemical tests for neuron specific enolase, chromogranin, and serotonin and by Grimelius method. Formalin fixed, paraffin-embedded sections from 60 prostatic carcinomas were used. EP cells were detected in 16 cases (27%). The number of EP cells in hormone independent prostatic carcinomas were significantly larger than hormone dependent (p less than 0.05) and latent prostatic carcinomas (p less than 0.01). Five cases of prostatic carcinomas with abundant EP cell proliferation died of widespread metastases within 4 years, irrespective of hormone treatment. The pathologic finding was classified into the category of adenocarcinoma, partly showing carcinoid or small cell carcinoma-like features. EP cells were found in perineural invading cancer cells and also immunoreactive to both prostate specific antigen and prostate specific acid phosphatase. It is suggested that the proliferation of EP cells in prostatic carcinomas is related with the sensitivity to hormone treatment.     

Severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant: a recurrent substitution in RAS homologs in various cancers

Activation of the RAS pathway through either the activation of genes that accelerate the pathway or the suppression of genes that inhibit the pathway leads to a group of disorders collectively referred to as RASopathies. The key molecules of the RAS pathway are KRAS, HRAS, and NRAS. Mutations in these three RAS homolog genes have been shown to be associated with RASopathies. Recently, two patients with a Noonan syndrome phenotype were shown to carry mutations in the yet another RASopathy gene, MRAS (muscle RAS oncogene homolog). Here, we report a patient with a severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant, which represents a recurrent substitution in RAS homologs in various cancers. The patient's dysmorphic features included relative macrocephaly, a down‐slanted palpebral fissure, hypertelorism, a depressed nasal bridge, and low‐set ears with thick lobes; these facial features are strongly associated with RASopathy. We confirmed that the MRAS gene represents a causative gene for RASopathy.