Ganglioneuroblastoma Associated with Malignant Hypertension and Cardiac Failure

Neuroblastoma is the most common extracranial solid tumor in children, and accompanies various clinical symptoms including hypertension. Hypertension is associated with catecholamines secreted from the tumor, and is usually not severe. We report one case of malignant hypertension with cardiac failure in a patient with adrenal neuroblastoma, successfully treated with adrenalectomy. A 3 year-old boy complained of protrusion of the chest wall. Physical examination revealed severe hypertension with cardiac failure. The levels of metabolites of catecholamine were increased in blood (norepinephrine >2000 pg/mL) and urine (norepinephrine 1350.5 ug/day). Abdominal CT showed a 7 cm-sized solid mass arising from the right adrenal gland. After stabilizing the hemodynamics with oral phenoxybenzamine, right adrenalectomy was performed. Pathological diagnosis was a ganglioneuroblastoma. The hypertension and cardiac failure were resolved after tumor removal.

A Cases of Paraganglioma in Bladder of Patient who Visited with Acute Renal Failure / 대한신장학회지

Pheochromocytoma is a catecholamines secreting tumor that usually appears in the adrenal medulla, sympathetic ganglia and extra-adrenal chromaffin tissue. About 10% of this disease is detected in the extra-adrenal chromaffin tissue which is called paraganglioma. The three major clinical symptoms of pheochromocytoma are headache, syncope and hypertension. Approximately 0.1% of hypertensive patients have pheochromocytoma. The extra-adrenal paraganglioma is found in abdominal sympathetic nerve ganglion or Zukerkandle's organ with great frequency, but it also appears, albeit rare, in the cervical ganglion, thoracic cavity, bladder, and pelvic cavity. Some cases of paraganglioma in bladder are being reported internationally, but domestic reports are rare. We report a case of paraganglioma originating in the urinary bladder of patient who visited with acute renal failure associated with malignant hypertension. We treated him with phenoxybenzamine and later with partial cystectomy. High blood pressure was well controlled and acute renal failure was resolved.

Pheochromocytoma in pregnancy: A case report / 대한내과학회지

Pheochromocytoma during pregnancy is very rarely discovered, and this condition is life threatening to both mother and fetus. Maternal and fetal survival depend a lot on an early diagnosis, a correct medical therapy and a correct timing of delivery and surgery. We describe a case of pheochromocytoma during pregnancy. A patient was transferred to our hospital during gestational week 24 with severe hypertension, generalized edema. Pheochromocytoma caused by a left adrenal mass was diagnosed. The patient was treated with titrated dose of phenoxybenzamine, propranolol, and intravenous nicardipine, but intermittent severe hypertension was developed. At 33 weeks gestation, fetal distress was developed, and emergent cesarean section was done. Two weeks after delivery, she underwent a successful left adrenalectomy. Two months after surgery, all antihypertensive medications were discontinued and her blood pressure have remained normal range.

The growth inhibition effect of alpha-adrenoceptor antagonists on androgen- independent prostate cancer cell line / 中华外科杂志

<p><b>OBJECTIVE</b>The aim of the present study is to compare the effects of two alpha1-adrenoceptor antagonist terazosin and alfuzosin together with one alpha-adrenoceptor antagonist phenoxybenzamine on androgen-independent prostate cancer cell lines PC-3 and DU145.</p><p><b>METHODS</b>Two androgen- independent cell lines, PC-3 and DU145, were used to determine the cell viability, colony-forming ability as well as cell cycle characteristics after exposure to these three drugs.</p><p><b>RESULTS</b>This study showed that terazosin inhibited not only prostate cancer cell growth but also colony-forming ability, which is the main target of clinical treatment. On the other hand, alfuzosin and phenoxybenzamine have no effect on cell viability and colony forming ability of PC-3 and DU145. In addition, the terazosin inhibits cell growth through G(1) phase cell cycle arrest.</p><p><b>CONCLUSION</b>This study provided the evidence that alpha1-adrenoceptor antagonist terazosin may have a therapeutic potential in the treatment of advanced androgen-independent prostate cancer.</p>

A Case of Pheochromocytoma Antenatally Diagnosed in the Mid Gestation / 대한주산의학회잡지

Pheochromocytoma during pregnancy is very rare tumor, and this condition is life threatening to both mother and fetus. We describe a case of pheochromocytoma antenatally diagnosed at the midtrimester in gestation. A patient was transferred to National Medical Center during gestational week 24 with severe hypertension, generalized edema. Pheochromocytoma caused by a left adrenal mass was diagnosed. The patient was treated with titrated dose of phenoxybenzamine, propranolol, and intravenous nicardipine, but, intermittent severe hypertension was developed. At 33 weeks gestation, fetal distress was developed, and emergent c-sec was done. Two weeks after delivery, she underwent a successful left adrenalectomy. Two months after surgery, all antihypertensive medications were discontinued and her blood pressure have remained normal range.

The discussion of standards for clinical functional gradation and preoperative preparation of pheochromocytoma / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the standards for clinical functional gradation and preoperative preparation of pheochromocytoma.</p><p><b>METHODS</b>According to the preoperative clinical manifestations and 24 hr urine catecholamine, 172 cases of pheochromocytomas were divided into 4 grades. Functionary grade 0 including 22 patients was given no volume expansion. Functionary Grade 1 consisted of 17 cases, 10 of which were given phenoxybenzamine orally 5 - 10 mg/d for 1 week (therapeutic group), the rest were control group; the results were analyzed by the chi(2) test. Functionary Grade 2 including 120 patients had phenoxybenzamine orally 30 - 240 mg/d for 4 weeks, hemodynamics and microcirculation image were standards for evaluating volume expansion. Functionary Grade 3 consisted of 13 patients including 1 with acute heart failure, 2 and 10 patients with past history of cerebral hemorrhage and hypertensive crisis respectively, they were treated with enough phenoxybenzamine and other emergent measures.</p><p><b>RESULTS</b>The perioperative blood pressure of Functionary Grade 0 had no fluctuation. The blood pressure of therapeutic group of Functionary Grade 1 had small range fluctuation (< 20 mm Hg), that of the control group was large (> 40 mm Hg). Chi(2) = 13.12, P < 0.01. The hemodynamics of Functionary Grade 2 and Grade 3 recovered within 24 hours postoperatively and no complications occurred.</p><p><b>CONCLUSION</b>According to the function of pheochromocytoma, it is safe and efficient to use different preoperative preparations. Hemodynamics and microcirculation image are golden standards for evaluating preoperative preparations.</p>

Analgesia in phasic and tonic pain tests in a pharmacological model of autotomy.

Self-mutilation or self-injurious behaviour is a well known behavioural disorder in humans. The proposition that this behaviour in animals is a response to chronic pain of peripheral nerve injury has been met with controversy. In the present study a pharmacological model, which produces no sensory or motor loss was used to study how autotomy is related to pain. In a group of rats autotomy was induced by amphetamine in phenoxybenzamine and reserpine treated animals. The pain tests, both phasic and tonic were then performed. The results of this study showed that a total analgesia was produced in both phasic and tonic pain tests, in animals that exhibited autotomy. Injection of naloxone in these animals prevented autotomy. A correlation between autotomy and no pain is suggested in this pharmacological model of autotomy.

Clinical Study of the Pheochromocytoma / 대한내분비학회지

BACKGROUND: Pheochromocytoma may arise within the adrenal medulla, or in other locations where sympathetic ganglia or chromaffin tissues are known to exist. Approximately 0.1% of hypertensive patients have pheochromocytoma. Most of this hypertension can be cured by surgical removal of the tumor, but lethal complication can develop if proper treatment is not prepared. Therefore, accurate diagnosis and preoperative preparation is very important. The objective of this study was to evaluate the clinical characteristics of pheochromocytoma and the blood pressure change following tumor removal. METHOD: The medical records of 45 patients [29 cases of intra-adrenal, 16 cases of extra-adrenal (paraganglioma)] diagnosed with of pheochromocytoma at Korea University Medical Center between 1991 and 2001 were reviewed. RESULTS: Twenty of the cases were male and 25 were female. The mean age of these patients was 43 years old. Hypertension, headaches, palpitations and impaired glucose tolerance were observed more frequently in cases of intra-adrenal tumor than in those of extra-adrenal. In the extra-adrenal group, abdominal pain, hypertension and nausea were more frequently observed. A biochemical study showed that the sensitivity of the test for catecholamines and metabolites in 24 hours urine was over 80%. For the localization of tumors we used abdominal CT and MIBG. The sensitivities of the CT and MIBG for the tumor localization were 97 and 91%, respectively. Blood pressures during the operations were effectively controlled by preoperative treatment with phenoxybenzamine (non-competitive, non-selective -adrenoreceptor antagonists). CONCLUSION: Surgical treatment cured 23 of the 30 cases of hypertension with pheochromocytoma. We have to take careful approaches in the care of the patient who may have pheochromocytoma, due to the various clinical signs and symptoms.

Pheochromocytoma Clinically unsuspected pheochromocytoma

PURPOSE: Pheochromocytoma is a catecholamine-secreting tumor that arises from the chromaffin cells of the sympathoadrenal system and presents with the typical symptoms of palpitation, diaphoresis, head ache, and hypertension. Some pheochromocytoma may be discovered during computed tomography of the abdomen while evaluating the abdomen and may be clinically unsuspected before surgery. The aim of this study was to analyze the clinical presentation of pheochromocytoma and to identify the charac teristics of clinically unsuspected pheochromocytomas. METHODS: From June 1995 to October 1999, 34 histopathologically confirmed pheochromocytomas were diagnosed at Samsung Medical Center, Seoul, Korea. The records of all 34 patients, who had undergone a surgical resection for pheochromocytoma and paraganglioma, were reviewed for demographic information, presenting signs and symptoms, bio chemical profiles that led to the laboratory diagnosis of pheochromocytoma, tumor localization studies, associated diseases, preoperative preparation, surgical procedures, and tumor pathology. RESULTS: The most prominent symptoms of pheochromocytomas was palpitation, which was present in 21 (62%) of the 34 cases. Hypertension, headache, and sweating were in 18 (53%), 17 (50%), and 9 (27%) patients, respectively. In 14 (41%) of the 34 patients, the pheochromocytoma were incidentally found exhibiting none of the typical symptoms. Eight (24%) were clinically unsuspected and were undiagnosed prior to surgery. A preoperative diagnosis of either retroperitoneal or pancreatic mass was made in six cases (18%), and a diagnosis of a nonfunctioning adrenal mass was made in two (6%). These eight patients underwent surgery without any preoperative pharmacological treatment. Sporadic cases accounted for 85% of the patients (29 patients), and associated conditions included MEN 2A in four (12%) and MEN 2B in one (3%).The sensitivities of the urinary evaluation were metanephrine 85%, norepinephrine 81%, epinephrine 73%, and vanillylmandelic acid (VMA) 73%. The combination of urinary metanephrine and VMA had a diagnostic sensitivity of 92%. The sensitivities of the localization modalities were CT 100%(33/33), MRI 100% (3/3). USG 94.8% (18/19), MIBG 70% (7/10). Four of the 8 patients who received no preoperative preparation and 10 of the 26 patients who received phenoxybenzamine daily for at least 2 weeks) had intraoperative hypertension or arrythmia. One patient received a laparoscopic adrenalectomy. The rest of the patients underwent surgery through open transabdominal incision. The mean tumor diameter of the malignant pheochromocytomas was 10.8 cm (range from 4.5 to 16 cm), and that of the benign pheochromocytoma was 6.1 cm (range from 3 to 10 cm) showing marked differences between two groups. This suggests that malignant tumors tend to be larger than benign tumors. Of the 4 malignant cases, recurrent disease occurred at the site of the original tumor in 1 patient, metastasis didnt occur in any case. CONCLUSION: High index of suspicion for a pheochromocytoma must be maintained in patients with retroperitonal and abdominal masses or isolated hypertension and in patients with multiple endocrine neoplasms. The readily available, sensitive assays for plasma and urinary catecholamines and their me tabolites and the newly developed modern imaging techniques, such as CT and I-131-MIBG, when used together, may help inmaking correct diagnosis of pheochromocytoma in patients without paroxysmal symptoms or hypertension.

A Case of Multiple Endocrine Neoplasia Neoplasia Type IIa Complicated by Acute Myocardial Infarction / 대한내분비학회지

MEN IIa is the rare disorder consisted of thyroid medullary carcinoma, pheochromocytoma, and hyperparathyroidism. We experienced the case in which 42 year-old male patient with thyroid medullary carcinoma and pheochromocytoma complicated by acute myocardial infarction. During the process of conventional treatment of acute myocardial infarction, paroxysmal hypertension occurred for several times. We sought for the cause of paroxysmal hypertension, and found pheochromocytoma by the radiologic imaging study and the biochemical study and we found the 4X4 cm sized neck mass by palpation. After stabilizing his blood pressure by the use of phenoxybenzamine, we removed the pheochromocytoma in right adrenal gland and the medullary thyroid cancer, by right adrenalectomy and total thyroidectomy respectively. Thereafter, his subjective symptoms and objective signs were improved. We report the case with review of literatures.

Influence of moderate cooling (37§C-25§C) on the reactivity of isolated rat tail artery

The aim of the investigation was to examine the effects of cooling on the tail artery regarding the scarceness of such studies in spite of the essential thermoregulatory role played by this vessel. Segments of the proximal portion were suspended isometrically in medium containig 1.25 mM Ca. Lowering the temperature to 25 degrees Celsius increased the sensitivity and maximum strength of the adrenaline concentration-effect curves. These changes were reversed by warming to 37 degrees Celsius. Cocaine attenuated the increase of sensitivity without changing the increase of the maximum response. Either the sensitivity and strength of the responses to phenylephrine and serotomin were increased by cooling. Clonidine evoked weak contractions in 18 out of 38 experiments. After cooling, the responses persisted only in 7 arteries and the strength was almost halved. Responses to field eletric stimulation at 25 degrees Celsius exhibited a pronounced increase of strength and a small increase of sensitivity. -log Kb for prazosin against adrenaline was encreased by cooling (8.7 and 9.1 at 37 degrees Celsius and 25 degrees Celsius C, P<0.01). After partial receptor inactivation using phenoxybenzamine, the dissociation-constant (KA) indicated a moderate affinity for phenylephrine that was not changed by cooling (4.1 and 4.2 x 10(-6) at 37 degrees Celsius respectively). Receptor reserve and occupancy at EC(50) also remained unchanged at 25 degrees Celsius. It can be concluded that: 1) cooling increases the tail artery reactivity, partly as a consequence of the inhibition of adrenergic neuronal uptake; 2) responsiveness to alpha 2-agonists is not in volved in the effects of cooling whereas the role of alpha 1-adrenoceptor could not be properly clarified; 3) cooling may facilitate some steps of the contractile activation beyond the agonist-receptor interaction.

Antinociception induced by stimulating amygdaloid nuclei in rats: changes produced by systemically administered antagonists

The antinociceptive effects of stimulating the medial (ME) and central (CE) nuclei of the amygdala in rats were evaluated by the changes in the latency for the tail withdrawal reflex to noxious heating of the skin. A 30-s period of sine-wave stimulation of the ME or CE produced a significant and short increase in the duration of tail flick latency. A 15-s period of stimulation was ineffective. Repeated stimulation of these nuclei at 48-h intervals produced progressively smaller effects. The antinociception evoked from the ME was significantly reduced by the previous systemic administration of naloxone, methysergide, atropine, phenoxybenzamine, and propranolol, but not by mecamylamine, all given at the dose of 1.0 mg/kg. Previous systemic administration of naloxone, atropine, and propranolol, but not methysergide, phenoxy-benzamine, or mecamylamine, was effective against the effects of stimulating the CE. We conclude that the antinociceptive effects of stimulating the ME involve at least opioid, serotonergic, adrenergic, and muscarinic cholinergic descending mechanisms. The effects of stimulating the CE involve at least opioid, beta-adrenergic, and muscarinic cholinergic descending mechanisms.

Hypotension Controlled by Infusion of Norepinephrine during Pheochromocytoma Excision: Case report / 대한마취과학회지

We report a case in which a 63-year-old male patient with pheochromocytoma developed persistent hypotension during surgery despite rapid volume replacement and administration of vasopressors. The patient was prepared for surgery with phenoxybenzamine for 13 days. Anesthesia was induced with thiopental sodium and maintained with N2O, O2, and enflurane. Sodium nitroprusside (SNP) was initiated and titrated based upon intraarterial blood pressure. Hypertensive episode during tumor manipulation was effectively managed by increased infusion of SNP. After surgical removal of tumor, this patient developed profound hypotension, which was aggressively managed by intravenous administration of crystalloid and blood as well as dopamine and epinephrine. However, this hypotension was persistent and aggravated. Accordingly, Infusion of norepinephrine (Levophed(R))was started and then the patient recoverd from his hemodynamic aberrations. We conclude that the cause of the persistent hypotension was cumulative and residual effect of preoperative phenoxybenzamine. Therefore, norepinephrine should be readily available for the treatment of hypotension resistant to other pharmacologic interventions.

Pressor Effect of Intracerebroventricular 4-Aminopyridine on the Systemic Arterial Pressure in the Rabbit

A K+-channel blocker, 4-aminopyridine(4-AP) increases neurotransmitter release from motor nerve terminals and has been shown to restore neuromuscular transmission in the myasthenic syndrome. It has been reported that the intravenous injection of 4-AP in the myasthenic patients caused many central adverse effects including anxiety and restlessness, but did not affect the blood pressure. The aim of this study was to observe the effect of intracerebroventricularly administered 4-AP on the blood pressure and to elucidate the mechanism of the action in urethane-anesthetized rabbits. Intracerebroventricular(icv) 4-AP produced pressor effects in a dose-dependent fashion, but intravenous(iv) 4-AP of the same dose did not altered the blood pressure. Tetraethylammonium, a K+-channel blocker which differs from 4-AP structurally, had little effect on the blood pressure, but 3,4-diaminopyridine, another derivative of the aminopyridine, produced pressor effect similar to 4-AP. The pressor effect of icv 4-AP was not affected by the treatment with iv phenoxybenzamine and chlorisondamine, and in bilateral adrenalectomized rabbits. These results suggest that the 4-AP pressor effect is not related to the periphral sympathetic nerve nor adrenal gland. The pretreatment with icv phentolamine and prazosin did not altered the 4-AP pressor. However, the icv 4-AP pressor effect was significantly attenuated by the treatment with icv yohimbine, and significantly potentiated by the treatment with icv clonidine. The treatment with icv diltiazem markedly inhibited the icv 4-AP pressor effect. It is concluded that 4-AP-sensitive K+-channels in rabbit brain might play a role in the regulation of blood pressure and that the 4-AP pressor effect is closely related to the central alpha2-adrenoceptors and L-type calcium channels.

Inhalation Anesthesia with Isoflurane for Surgical Removal of Pheochromocytoma / 대한마취과학회지

We have experienced an anesthetic management of a 34 year old female patient with pheochromocytoma of left adrenal gland. The anesthetic management of patients presents many difficult problems, such as hypertension, arrhythmia and hypotension. The patient had been treated with phenoxybenzamine for 2 weeks preoperatively. Following induction of anesthesia with intravenous fentanyl, thiopental sodium and vecuronium, endotracheal intubation was performed. Anesthesia was maintained with nitrous oxide, oxygen and isoflurane administration. Blood pressure and pulse were controlled well with nitroprusside and isoflurane. After removal of tumor, blood pressure was controlled by Hartman's solution, packed red cell and dopamine administration. The patient tolerated well despite the episodic hemodynamic changes. Importance of preoperative preparation, sufficient sedation, smooth induction, complete analgesia, good muscle relaxation and stable cardiovascular control has been discussed.

Anesthetic Experiences for Resection of Bilateral Pheochromocytoma: Two cases / 대한마취과학회지

We had experienced anesthetic management of two patients with bilateral pheochromocytoma. They had been treated with phenoxybenzamine for 4 weeks preoperatively. Anesthesia was managed with thiopental sodium for induction,enflurane-N2O-O2 for maintenance, vecuronium for muscle relaxation, and sodium nitroprusside for controlling severe hypertension. After tumor resection, severe hypotension was controlled by rapid transfusion, fluid and dopamine infusion. A tolerable blood pressure and pulse rate were maintained throughout the procedure. Preoperative preparation, sufficient sedation, smooth anesthetic induction, complete analgesia, good muscle relaxation, adequate ventilation and proper cardiovascular control are required in resection of pheochromocytoma.

Antinociceptive effects of stimulation of discrete sites in the rat hypothalamus: evidence for the participation of the lateral hypothalamus area in descending pain suppression mechanisms

The sites in the rat hypothalamus where microinjection of morphine 5 mug/0.5 mul) or electrical stimulation depresses the tail withdrawal reflex to noxious heating of the skin were examined. Among other hypothalamic sites found to be sensitive to morphine or to an electrical stimulus, the posterior part of the lateral hypothalamic area (LHA) was the only portion of the hypothalamus that was strongly sensitive to both manipulations. A 15-sec period of 35-muA sine-wave stimulation of the LHA significantly increased the latency of the tail reflex for periods up to 30 min. The effects of intraperitoneal administration of antagonists to opioids (naloxone), 5-hydroxytryptamine (methysergide), noradrenaline (phenoxybenzarnine), dopamine (haloperidol and acetylcholine (atropine and mecamylamine) on the antinociceptive effects of LHA stimulation were also examined. Naloxone, methysergide, and atropine (all given at doses of 0.5 and 1.0 mg/kg attenuated the effects of LHA stimulation in a dose-dependent manner. Phenoxybenzamine, but not haloperidol (both at the dose of 1.0 mg/kg), was also effective but dose-dependent curves could not be constructed. Mecamylamine (1.0 mg/kg) reduced the duration but no the peak effect of stimulating the LHA. We conclude that antagonism at the level of opioid, serotonergic, adrenergic, and muscarinic cholinergic receptors, but not dopamine or nicotinic cholinergic receptors reduces the antinociceptive effects of LHA stimulation. This may imply that antinociception evoked from the LHA depends on the activation of descending pathways that relay in the mesencephalic periaqueductal gray matter and then in the nucleus raphe magnus and/or nucleus reticularis paragigantocellularis.

Effect of Chemical Sympathectomy and Laser Radiation in the Neuropathic Pain / 대한마취과학회지

BACKGROUND: Treatments of neuropathic pain were included Ca blocker, steroid medication, epidural or spinal local anesthetics, intravenous reserpine and phenoxybenzamine and operative sympathectomy. This study was performed to evaluation the effects of laser radiation and intraperitoneal guanethidine to the neuropathic pain. METHODS: The neuropathic pain were produced by the tight ligation of L5 and L6 spinal nerves in the adult rats (Sprague-Dawley) withdrawl response to the non-noxious stimulation(mechanical allodynia) were increased and response to the cold stimulation (cold allodynia) were increased too. After that, we injected 50 mg/kg guanethidine intraperitoneally and radiated the He-Ne laser to the operated site to evaluate the effect of chemical sympathectomy and laser radiation. RESULTS: Mechanical allodynia was significantly reduced(p<0.05) 1st and 2nd day after chemical sympathectomy. Cold allodynia was significantly reduced(p<0.05) 1st day after chemical sympathectomy. Mechanical and cold allodynia were not significantly reduced after laser radiation. CONCLUSIONS: It was suggested that the chemical sympathectomy via intraperitoneal injection of guanethidine 50 mg/kg had the therapeutic effect of neuropathic pain in the surgically operated rat which was ligated L5, 6 spinal nerve.

Myocardial infarction in a Pregnant Woman with Pheochromocytoma / 대한마취과학회지

A 36-year-old woman (para 1-0-2-1) was transferred to Korea University Hospital at 38 weeks gestation for dyspnea and chest pain. On admission, her blood pressure ranged from 130/ 70 to 230/130 mmHg, the heart rate was 144 beats/min and respiratory rate was 36/min. The ECG pattern, serum creatinine phosphokinase and lactic dehydrogenase levels were consistent with acute myocardial infarction. The baby was delivered by cesarean section under general anesthesia with nitroglycerin and propranolol support, After delivery, the patient was diagnosed as having pheochromocytoma by hormone study, abdominal magnetic resonance imaging, and computerized tomography scan. Removal of tumor was suceessfully done under combined general and epidural anesthesia after preoperative preparation with phenoxybenzamine and propranolol for two weeks. Postanesthetic recovery was uneventful.