Brown tumor of bone: a potential source of false-positive thallium-201 localization.

Brown tumor of bone (osteitis fibrosa cystica) should be included in the differential diagnosis of lesions that cause false-positive thallium-201 localization in patients with primary hyperparathyroidism. We report a case of a brown tumor of the upper sternum mimicking a superior mediastinal parathyroid neoplasm in a patient with persistent hyperparathyroidism 9 years after a negative neck exploration (with subtotal thyroidectomy and thymectomy). A 201TI/99mTc pertechnetate subtraction scintigram demonstrated complete subtraction of this 201TI focus.

Comparison of 99mTc-methoxyisobutyl isonitrile and 201Tl scintigraphy for detection of residual thyroid cancer after 131I ablative therapy.

UNLABELLED: In this study, we compared 99mTc-methoxyisobutyl isonitrile (MIBI) with 201Tl scintigraphy for the detection of residual thyroid cancer not found by 131I scans in patients with increased risk of recurrence after 131I therapy. METHODS: 201Tl and MIBI scans were obtained in 54 patients with negative 131I scans 3-25 y (median 7.9 y) after the first postsurgical 131I therapy. Serum thyroglobulin (Tg) levels were measured while patients were receiving thyroid hormone and again 6 wk after withdrawal of hormone therapy. RESULTS: The overall results were the same for both 201Tl and MIBI imaging, with a sensitivity of 19 of 36 (53%), specificity of 17 of 17 (100%) and accuracy of 36 of 54 (69%). Planar images missed residual cancer in high cervical lymph nodes adjacent to salivary gland activity, in small nodes (<1 cm) deep in the neck or chest and with diffuse pulmonary micrometastases. Serum Tg was elevated in 24 of 36 (67%) patients with residual cancer; 201Tl detected tumor sites in 13 of 24 (54%) of these patients, and MIBI detected tumor sites in 14 of 24 (58%) of these patients. Of the 12 patients who had residual cancer and false-negative serum Tg levels, 6 had true-positive 201Tl and 5 had true-positive MIBI scans. CONCLUSION: 201Tl and MIBI planar imaging yield the same high specificity and positive predictive value for residual thyroid cancer in patients with high-risk profiles and negative radioiodide scans. Both imaging agents detected residual cancer in more than half of the patients in whom conventional staging techniques did not reliably detect either the presence or the extent of residual thyroid cancer and changed the management in patients with surgically resectable cancer.

Insular carcinoma: a distinct thyroid carcinoma with associated iodine-131 localization.

Insular carcinoma, once considered a poorly-differentiated thyroid cancer, has been reclassified as a distinct thyroid neoplasm. Since this neoplasm is composed of follicular epithelial cells, it may concentrate radioiodide (131I) making postoperative 131I imaging for detection of metastases and radiotherapy possible. A 20-yr review of 35 cases diagnosed as anaplastic or undifferentiated thyroid carcinoma at this medical center revealed five patients with insular carcinoma. Four patients showed postoperative 131I localization and received therapeutic doses of 131I. Three of the four showed extrathyroidal 131I localization in neoplastic lesions. In one patient, the resolution of metastatic lesions by magnetic resonance and 131I imaging suggests that 131I may have an important therapeutic role in this aggressive neoplasm.

The role of acid and ischemia in production of stress ulcers during canine hemorrhagic shock.

Hemorrhage to a mean arterial pressure of 41 mm. Hg in ten dogs decreased Heidenhain pouch blood flow to 6 ml. per minute and aminopyrine clearance to 0.93 ml. per minute. Pouch oxygen consumption fell from 1.47 to 0.74 ml./min.-100 Gm. and total body oxygen consumption remained unchanged. Net ion fluxes during shock and reinfusion did not change significantly from control values of minus 89.8 muGq./30 min.-100 cm.-2 for H-+ and 88.6 muEq./30 min.-100 cm-2 for Na-+. However, PD decreased from 54 to 24 mv. in parallel with a fall in net Cl-minus flux from 56.8 to minus 11.7 muEq./30 min.-100 cm-2. Nine of ten pouches subjected to shock and instilled acid test solution (ATS) developed superficial mucosal erosions. No ulcerations were found in either seven control dogs (anesthesia + ATS) or in three dogs subjected to shock without ATS. Acid appears to be of prime importance in the production of stress ulcers during or following ischemia, even though there is no increase in mucosal ionic permeability.

Opiate receptors and endorphins in the pathophysiology of hemorrhagic shock.

We investigated the hypothesis that endorphins released by stress act on opiate receptors to depress cardiovascular function during hemorrhagic shock. Anesthetized adult mongrel dogs were bled into a heparinized reservoir to achieve a mean arterial pressure (MAP) of 45 mm Hg. The reservoir was adjusted to maintain MAP for 1 hour and then clamped for 1 hour, at the end of which time the shed blood was reinfused. While the reservoir was clamped we treated the animals with an intravenous bolus followed by 3-hour infusion of either 0.9% NaCl (as control) or the specific opiate receptor antagonist naloxone at three dose regimens (0.5, 1, or 2 mg/kg plus 0.5, 1, or 2 mg/kg . hr). Naloxone produced dose-dependent increases in MAP, cardiac output, stroke volume, and left ventricular contractility. Survival at 72 hours was related to the dose of naloxone used. None of six dogs treated at 0 mg/kg . hr survived, one of six survived at 0.5 mg/kg . hr, four of five at 1 mg/kg . hr, and five of five at 2 mg/kg . hr. Since naloxone has minimal effect on cardiovascular function in nonshocked dogs, these results implicate opiate receptors and perhaps endorphins in the cardiovascular pathophysiology of hemorrhagic shock.

Effects of cholesterol gallstone induction on gallbladder function and bile salt pool size in the prairie dog model.

The prairie dog gallstone model was used to test the following hypotheses: (1) gallbladder stasis occurs in association with gallstone formation, and (2) bile salt pool size decreases as gallstones develop. Bile salt pool sizes and the extent of equilibration of hepatic and gallbladder bile salt over the course of gallstone development were measured. No evidence for bile salt pool reduction was found, but there was significant evidence of progressively inefficient equilibration of hepatic and gallbladder bile salt very early during gallstone formation. These changes, suggestive of gallbladder stasis and observed only in the presence of cholesterol crystals in bile, persisted as cholesterol stones developed and antedated any reduction in bile salt pool size.

Autonomic effects of central injections of D-Ala2-Met-enkephalinamide (DAME) in the conscious monkey.

The use of naloxone (NAL), an opioid receptor antagonist, has provided indirect evidence that endogenous opioids contribute to cardiovascular depression during shock. To determine if endogenous opioids act centrally to influence cardiovascular function, injections of D-Ala2-Met-enkephalinamide (DAME), a potent Met-enkephalin analog, were made into the 3rd cerebral ventricle (ICV) of 5 conscious cynomulgus monkeys restrained in primate chairs. Systolic blood pressure (SBP) and heart rate (HR) were determined every 10 min during a 30-60 min control period and for up to 5 hr post-injection. Colonic temperature (Tc) was monitored continuously. SBP declined from baseline values with 50 and 100 micrograms (85.2 and 170.4 nM) doses but was significant (p less than 0.001) for only the 100 micrograms dose between 15-125 min post-injection. HR also decreased but did not exhibit any significant variation with time. However, when averaged across time, HR fell significantly (p less than 0.001) from baseline: -9.1 +/- 2.3 and -15.0 +/- 2.1 b/min for 50 and 100 micrograms DAME, respectively. Tc displayed a nonsignificant, delayed (greater than 2 hr) rise in Tc with the 50 micrograms dose, whereas the 100 micrograms dose caused a significant (p less than 0.001) decline in Tc (from 65-125 min post-injection). NAL injected ICV attenuated the effects of DAME but had no effect on SBP, HR or Tc when injected alone. Systemic injection of DAME (300 micrograms) in one monkey produced a transient decline in SBP (26 mmHg within 2 min) which returned to baseline values 4 min post-injection. HR and Tc were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of opiate receptor drugs injected intracerebrally into the normovolemic and hypovolemic monkey.

Systemic injection of naloxone (NAL), an opioid-receptor antagonist, significantly elevates systolic blood pressure (SBP) in anesthetized hypovolemic monkeys, providing indirect evidence that endogenous opioids contribute to cardiovascular depression during shock. The purpose of this study was to identify specific centrally located opioid receptor sites that participate in SBP regulation under normovolemic and hypovolemic conditions. In 6 monkeys, bilateral guide cannulae were stereotaxically implanted above areas ranging from the diencephalon to the lower medulla. Microinjections (1 microliter) of D- Ala2-Met-enkephalinamide (DAME) (3.4-27.2 nM) into normovolemic unanesthetized monkeys reduced SBP by 10-65 mm Hg in a dose-related fashion. Subsequent injection of NAL (12.2 nM) attenuated this hypotensive response. Heart rate fell 20-40 bpm with DAME, but not in response to dose. In the anesthetized animal rendered hypotensive (SBP = 45 mm Hg) by hemorrhage. NAL injected into predetermined DAME-sensitive sites failed to increase SBP more than 5 mm Hg. Even consecutive injections into multiple sites elevated SBP only 20 mm Hg. We conclude that the centrally located opioid-sensitive sites tested exert only a mild influence in mediating hemorrhagic hypotension.

Cytogenetic abnormalities in tumors of patients with von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that causes the development of benign and malignant tumors in several organ systems. Tumors causing significant morbidity include retinal angioma, cerebellar hemangioblastoma (CH), renal cell carcinoma (RCC), and pheochromocytoma (Pheo). Cytogenetic studies of tumors in VHL patients are rare. Cytogenetic findings in tumors from 12 patients with VHL disease, including four RCCs, three CHs, and five Pheos are presented. Three of the four RCC cases were abnormal. Monosomy 3 or a deletion of 3p was present in all three abnormal cases. Complete or partial trisomy of chromosome 5 was present in two cases. A deletion of 14q, trisomy 7, and a missing Y were each observed in one case. These findings indicate that a deletion of 3p may be a primary cytogenetic change in RCCs associated with VHL disease in addition to playing a role in sporadic RCC. Duplications of 5q and deletions of 14q may be important secondary changes in the progression of the malignant phenotype. No visible cytogenetic abnormalities were observed in the three CHs, or in four of the Pheos. One of the five Pheos was found to exhibit mosaic trisomy 7; its significance is unclear at the present time.

Hemodynamic changes following corticosteroid and naloxone infusion in dogs subjected to hypovolemic shock without resuscitation.

B-endorphin, which is released concomitantly with ACTH from the pituitary during stress, may also alter cardiac performance in hemorrhagic shock. In this study of 36 dogs subjected to hemorrhagic shock without resuscitation, we demonstrate the interaction of high doses of dexamethasone (DEX) or methylprednisolone (M) and opiate receptor blockade with naloxone (NAL). NAL, when given alone, resulted in the most hemodynamic improvement and the longest survival time while those animals receiving DEX or M, even in combination with NAL, did not do as well. These data suggest that corticosteroids block the NAL effect following hemorrhagic shock.

The therapeutic efficacy of opiate antagonists in hemorrhagic shock.

The endogenous opioids have been implicated as contributing factors to the cardiovascular dysfunction of shock. Opiate receptor antagonists improve cardiovascular function and long-term survival in laboratory animal models of shock. In this communication, evidence of the therapeutic efficacy of opiate antagonists in canine and primate hemorrhagic shock is presented. The animals were hemorrhaged into a reservoir to lower MAP to 45 mmHg and that pressure was maintained for 1 h at which time the reservoir was clamped and treatment initiated. The "shed blood" was returned at t = 120 min and treatment continued until t = 180 min. Opiate antagonists employed included naloxone, naltrexone and the mixed agonist/antagonist agent, nalbuphine. Both naloxone and naltrexone improved cardiac function at doses of 1 and 2 mg/kg. Animal survival was significantly enhanced in the high dose format. Nalbuphine also improved cardiovascular performance at doses from 1 to 4 mg/kg but at higher doses it depressed cardiac performance. The efficacy of the antagonists is attenuated by acidosis and hypothermia. Opiate antagonists may induce cardiac arrhythmias in combination with beta-adrenergic blocking drugs and the efficacy is reduced in animals that received high dose steroid therapy. Thus the use of opiate antagonists would be contraindicated in patients that received drugs such as propranolol or methylprednisolone. There have been no controlled clinical trials of opiate antagonists in human hemorrhagic shock; these are needed for final clarification.

A controlled clinical trial of whole gut lavage as a method of bowel preparation for colonic operations.

In a prospective randomized clinical trial, whole gut lavage was evaluated against conventional mechanical cleansing for colonic operations. The lavage took less time to perform, was better tolerated by patients, and resulted in more satisfactory preparation as judged by frequency of collapsed intestines. There was no difference in the outcome in the two series as measured by wound infection rate and length of hospitalization. It is concluded that whole gut lavage is as good as conventional mechanical cleansing but surpasses the latter in logistic advantages.

Stress ulceration and the gastric mucosal barrier.

The role of the gastric mucosal barrier in the pathogenesis of post-traumatic stress ulcerations is far from clear. Clinical studies on critically ill patients have shown disrupted gastric mucosal barriers with hydrogen ion back diffusion, but no correlation has been made between these findings and gastric erosions. In addition, numerous assumptions concerning gastric secretions, pyloric loss and esophageal contributions to the assayed gastric juice have to be made in these patients. There is contradictory experimental evidence concerning the theory that gastric mucosal ischemia or hypotension disrupts the normal gastric mucosal barrier. In subhuman primate studies, there is no increased back diffusion acid during hypotension or during the reinfusion periods. Even though there may not be increased permeability to H+, the presence of acid is a requirement for the development of stress ulcerations. The role of agents such as bile salts and aspirin is clearer. If these agents are present, increased back diffusion of acid is likely, but its role in the pathophysiology of post-traumatic gastric erosion awaits further clarification.

Tc-99m MIBI scintigraphic detection of metastatic insular thyroid carcinoma.

Thallium-201 and, recently, Tc-99m MIBI have been used in conjunction with I-131 scintigraphy for follow-up of patients with well-differentiated thyroid cancer. Insular carcinoma of the thyroid is a fairly aggressive thyroid neoplasm that is believed to arise from follicular cells and usually concentrates I-131. The authors report a patient with recurrent insular thyroid carcinoma in whom bilateral adrenal and lung metastatic lesions developed 3 years after ablative I-131 therapy for cervical lymph node and skeletal metastases. Tc-99m MIBI planar and SPECT images demonstrated these new lesions better than pretherapy I-131 scintigraphy and affords an imaging technique for post-I-131 therapy follow-up that does not require withholding thyroid hormone suppression.

Naloxone in endotoxic shock: experimental models and clinical perspective.

Naloxone has been used as a pharmacological tool to investigate the role of endorphins and opiate receptors in the cardiovascular pathophysiology of shock. It would appear that endorphins act on opiate receptors to contribute to the abnormalities found and that naloxone improves survival as well as cardiovascular function in shock. Preliminary studies in humans and the subhuman primate create cautious optimism regarding the clinical application of this information. Naloxone has served us well as a key to unlock the involvement of endorphins and opiate receptors in shock. However, further advances in our understanding may depend on the development and use of opiate receptor agonists and antagonists specific for the different opiate receptors described, each subserving different functions. Naloxone's disadvantage of increasing pain awareness may limit its clinical usefulness but might be overcome by using drugs that reverse the behavioral and neuroendocrine changes produced by beta-endorphin without altering pain relief. Thyrotropin-releasing hormone (TRH) is just such a "physiological" opiate antagonist which has been shown to increase MAP in experimental endotoxic and hemorrhagic shock [32].

Diagnostic and therapeutic considerations for fecal impaction.

During an 18-month period, 18 patients were admitted to the Beth Israel Hospital because of fecal impaction or its complications. The records of the 18 patients were reviewed to determine the presenting signs and symptoms, radiologic findings, course and etiology of fecal impaction. Prior use of drugs that slow gastrointestinal motility was found in seven cases, and seven of the 18 patients had severe neuropsychiatric illness. The presenting signs and symptoms in almost all instances were consistent with a diagnosis of intestinal obstruction. The difficulty in differentiating intestinal obstruction caused by fecal impaction from obstruction resulting from other lesions is discussed. The diagnosis of fecal impaction should be entertained only after other causes of intestinal obstruction have been excluded.