Quantification of salivary gland function in thyroid cancer patients treated with radioiodine

PURPOSE: Damage to salivary gland function following external irradiation has been documented. However, the extent of damage following radioiodine (131I) therapy for thyroid cancer has not been adequately studied. We evaluated salivary dysfunction in Ca-thyroid patients treated with therapeutic doses of 131I. METHODS AND MATERIALS: A simple acquisition and analysis protocol using 99mTcO4- (pertechnatate) and a gamma camera computer system was planned. The uptake of 99mTcO4- by the salivary glands at 10 min and percent of excretion of 99mTcO4- from the glands in response to a sialogogue (lemon juice) was studied in 33 patients treated with 1.369-38.702 GBq of 131I (Mean = 10.16 GBq, standard deviation = 7.659 GBq) in addition to 14 athyreotic controls. RESULTS: Significant damage to the salivary gland in terms of abnormal percent uptake or excretion was noted in 72.73% of the patients. Forty-eight percent of the patients treated with 131I showed asymmetrical involvement of the salivary complexes as opposed to none of the controls. Reduction in uptake of 99mTc4- or response to sialogogue was dose dependent, being more marked with higher radioiodine doses. Parotid glands were more affected than submandibular glands following 131I therapy. CONCLUSIONS: 131I therapy produces a significant effect on salivary gland function that is dose related and becomes evident over a period of several months after treatment.     

In vitro effect of cyclophosphamide on the binding of radiopharmaceuticals (99mTcO4- and 99mTc-MDP) to blood elements

Sodium pertechnetate (99mTcO4-) and many 99mTc-products are the radiopharmaceuticals most frequently used in nuclear medicine. Using an in vitro model, we evaluated the effect of cyclophosphamide on percent radioactivity of 99mTcO4- and methylenediphosphonic acid (99mTc-MDP) bound to isolated blood elements. Blood samples were incubated with the two radiopharmaceuticals, plasma and blood cells were separated and precipitated, and soluble and insoluble fractions were separated. To evaluate the effect of cyclophosphamide, blood was incubated with this drug 1 h prior to the addition of the radiopharmaceuticals. The fraction of 99mTcO4- radioactivity was slightly higher in plasma (61.2 to 53.8%) than in blood cells (38.8 to 46.2%) up to 6 h and cyclophosphamide did not interfere with this distribution. The amount of 99mTc-MDP radioactivity was higher in plasma (91.1 to 87.2%) than in blood cells (8.9 to 12.8%) up to 24 h and cyclophosphamide did not modify it. The binding of 99mTcO4- to the insoluble fraction of plasma (4.9 to 6.1%) was low and cyclophosphamide did not interfere with it up to 6 h, but a small blockade (9.8 to 4.8%) was observed at 24 h. From 3 h on, cyclophosphamide slightly inhibited 99mTcO4- binding to blood cells (23.1 to 16.6%) and increased it at 24 h (31.2 to 14.3%). Cyclophosphamide did not alter 99mTc-MDP binding to the insoluble fraction of blood cells and slightly decreased 99mTc-MDP binding to the insoluble fraction of plasma (29.8 to 23.6%) up to 6 h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparing the severity of obstructive sleep apnea in patients referred by urban and rural physicians

The occurrence of a subdural hematoma caused by the rupture of an intracranial aneurysm is rare. In our case, the patient is a 43-year-old woman who suffered from sudden onset of severe headache. Computed tomographic (CT) scan disclosed a subdural hematoma associated with subarachnoid hemorrhage. CT angiography and digital subtraction angiography revealed an elongated aneurysm adhering to the dura in the left Sylvian fissure. The subdural hematoma was evacuated and the aneurysm clipped. The patient made a full recovery.     

Combining endovascular and neurosurgical treatments of high-risk dural arteriovenous fistulas in the lateral sinus and the confluence of the sinuses

OBJECT: The authors describe the use of a systemic approach to treat dural arteriovenous fistulas (DAVFs) in the lateral sinus and the confluence of sinuses in 17 patients who presented with signs and symptoms related to intracranial hemorrhage, infarction, and diffuse brain swelling. METHODS: Angiographic examination revealed three different types of DAVFs in these high-risk patients: 1) extremely high flow DAVF not associated with sinus occlusion or leptomeningeal retrograde venous drainage (LRVD); 2) localized DAVF with exclusive LRVD and without sinus occlusion; and 3) diffuse DAVF with sinus occlusion and LRVD. Because of the complex nature of these lesions, the authors adopted a staged protocol in which they combined endovascular and surgical treatments. CONCLUSIONS: The authors believe that by close collaboration between endovascular therapists and vascular neurosurgeons, high-risk DAVFs in the lateral sinus and the confluence of sinuses can be successfully managed without treatment-related morbidity and mortality.     

Novel 99mTc aminobisthiolato/monothiolato "3 + 1" mixed ligand complexes: structure-activity relationships and preliminary in vivo validation as brain blood flow imaging agents

A series of neutral, lipophilic 99mTc mixed-ligand complexes of the general formula 99mTcOL1L2, where L1H2 is an N-substituted bis-(2-mercaptoethyl)amine, [X-CH2CH2N(CH2CH2SH)2], [SNS], and L2H is a monodentate thiol (RSH), [S], has been synthesized and evaluated in rodents for potential use in brain blood flow imaging. The complexes were prepared by ligand exchange reaction using 99mTc(V)O-glucoheptonate as precursor and equimolar quantities of the two ligands. In all cases the syn isomer was formed in a high yield, whereas the anti isomer was not always present. The formation of two isomeric complexes-syn and anti-was expected, since the N-substituent (X-CH2CH2N) can assume syn or anti configuration with respect to the 99mTcO3+ core during complexation. One anti and all syn isomers were isolated by HPLC. Their identity was confirmed by comparative HPLC studies with the analogous 99Tc complexes of established structure. In vivo distribution, in particular brain uptake and retention, greatly depended on the type of either tridentate (L1H2) or monodentate (L2H) ligand. All 99mTc complexes showed significant brain uptake in mice (0.78-4.35% injected dose per organ at 5 min postinjection). This initial uptake remained nearly constant for at least 30 min for most of the complexes. Structure-activity relationships of novel 99mTc(V)O SNS/S complexes in mice are reported and discussed. Selected complexes were further studied in rats. High brain uptake, comparable to that of 99mTc-d,l-HMPAO, and sufficient retention 60 min postinjection were provided with complex 18 [X = (C2H5)2N and R = p-CH3OC6H4CH2].     

Fetal intracranial hemorrhage. Imaging by ultrasound and magnetic resonance imaging

OBJECTIVE: To describe the magnetic resonance imaging (MRI) findings associated with fetal intracranial hemorrhage and to compare them with ultrasound findings. STUDY DESIGN: In four pregnancies complicated by fetal intracranial hemorrhage, fetal imaging was carried out using T2-weighted fast spin echo sequences and T1-weighted fast low angle shot imaging sequences and by transabdominal ultrasonography. RESULTS: An antepartum diagnosis of hemorrhage was made by ultrasound in one case and by MRI in two. Retrospectively, the hemorrhagic area could be identified from the MRI images in an additional two cases and from the ultrasound images in one case. In the cases of intraventricular hemorrhage, the MRI signal intensity in the T1-weighted images was increased in the hemorrhagic area as compared to the contralateral ventricle and brain parenchyma. In a case with subdural hemorrhage, T2-weighted MRI signals from the hemorrhagic area changed from low-to high-intensity signals during four weeks of follow-up. Better imaging of the intracranial anatomy was possible by MRI than by transabdominal ultrasonography. CONCLUSION: MRI can be used for imaging and dating fetal intracranial hemorrhages. Variable ultrasound and MRI findings are associated with this complication, depending on the age and location of the hemorrhage.     

Oral keratinocyte immune responses in HIV-associated candidiasis

Technetium-99m is the most commonly used radionuclide in routine nuclear medicine imaging procedures. Development of 99mTc-labeled receptor-specific imaging agents for studying the central nervous system is potentially useful for evaluation of brain function in normal and disease states. A novel 99mTc-labeled tropane derivative, [99mTc]TRODAT-1, which is useful as a potential CNS dopamine transporter imaging agent, was evaluated and characterized. After i. v. injection into rats, [99mTc]TRODAT-1 displayed specific brain uptake in the rat striatal region (striatum-cerebellum/cerebellum ratio 1.8 at 60 min), where dopamine neurons are concentrated. The specific striatal uptake could be blocked by pretreating rats with a dose of competing dopamine transporter ligand, beta-CIT (or RTI-55, i.v., 1 mg/kg). However, the specific striatal uptake of [99mTc]TRODAT-1 was not affected by co-injection of excess free ligand (TRODAT-1, up to 200 microg per rat) or by pretreating the rats with haloperidol (i.v., 1 mg/kg). The specific uptake in striatal regions of rats that had prior 6-hydroxydopamine lesion in the substantia nigra area showed a dramatic reduction. The radioactive material recovered from the rat striatal homogenates at 60 min after i.v. injection of [99mTc]TRODAT-1 showed primarily the original compound (>95%), a good indication of in vivo stability in brain tissue. Similar and comparable organ distribution patterns and brain regional uptakes of [99mTc]TRODAT-1 were obtained for male and female rats. Ex vivo autoradiography results of rat brain sections further confirmed the high uptake and retention of [99mTc]TRODAT-1 in the striatal region. In vitro binding studies measuring the affinity to dopamine transporters for the free ligand, TRODAT-1, and a nonradioactive rhenium derivative, Re-TRODAT-1, showed Ki values of 9.7 nM and 14.1 nM, respectively. Behavioral studies in rats using the free ligand, TRODAT-1 and Re-TRODAT-1 indicated that, unlike other tropane derivatives, they displayed no effect on locomotor activity, suggesting low toxicity. These results strongly support the conclusions that this novel 99mTc radioligand binds selectively to dopamine transporters in the brain and that is is potentially useful for in vivo assessment of the loss of dopamine neurons in Parkinson's and other neurodegenerative diseases.     

Dental health amongst 11-15-year-old children in Sevagram, Maharashtra

Although most subdural hematomas are considered to be venous in origin, they may also be of arterial origin. When subdural bleeding is due to the rupture of an intracranial aneurysm, most commonly at the middle cerebral or internal carotid arteries, the amount of subdural blood is usually small and of no clinical importance. We describe two patients with subdural hematomas secondary to rupture of an intracranial aneurysm, who needed prompt surgical treatment. The first patient had a left internal carotid artery aneurysm at the origin of the ophthalmic artery. In the second patient the aneurysm was at the anterior communicating artery and rebled into the subdural space directly through a right intraparenchymatous frontobasal hematoma. The most probable mechanism of subdural bleeding in our two patients was the existence of adhesions between the aneurysm and the arachnoid due to previous minor hemorrhages. The indication of cerebral angiography in a patient with subdural hematoma is based mainly upon the existence of meningeal signs, the presence of blood in more than one intracranial compartment or the rapid progression of bleeding.     

Transcranial Doppler for early identification of potential organ transplant donors

BACKGROUND: Encouraging results in transplant medicine create a growing demand for organ transplant donors. Transcranial Doppler (TCD) has been used by several investigators to assess arrest of the cerebral circulation in brain dead patients. We report on TCD as a monitoring tool for early identification of potential organ transplant donors. DESIGN: A prospective clinical study. SETTING: Intensive care unit (ICU) of a 900-bed community hospital (primary and tertiary care center) in Vienna, Austria. SUBJECTS AND METHODS: All patients with acute intracranial lesions admitted to our intensive care unit underwent TCD examination at least once daily. In patients with Glasgow Coma Scores < 7, TCD waveforms with high resistance profiles unchanged by therapeutic attempts to lower intracranial pressure indicated the need for repeated TCD up to four times a day. TCD waveform abnormality consisting of absent or reversed diastolic flow or small early systolic spikes in at least two intracranial arteries was considered to constitute intracranial circulatory arrest. Brain death was confirmed by clinical criteria, an isoelectric electroencephalography (EEG) or non filling of the intracerebral arteries on arteriography. RESULTS: From January 1994 to July 1996 we identified 11 comatose patients as potential organ transplant donors with typical TCD findings indicating intracranial circulatory arrest. Diagnosis was subarachnoid hemorrhage in 7 and intracerebral hemorrhage in 4 patients. Brain death diagnosis according to the criteria of Austrian law was initiated immediately after the TCD findings suggested intracranial circulatory arrest. Confirmation of brain death was obtained by clinical criteria and either EEG (6 patients) or cerebral angiography (5 patients). CONCLUSION: TCD examinations on a daily routine basis offer a noninvasive monitoring method for early assessment of intracranial circulatory arrest. TCD enables quick identification and further diagnosis of candidates for organ transplant donation.     

Bis(dithiocarbamato) nitrido technetium-99m radiopharmaceuticals: a class of neutral myocardial imaging agents

The synthesis and biodistribution in various animal models (rat, dog, pig and monkey) of 99mTc radiopharmaceuticals containing the Tc = N multiple bond are reported. METHODS: The complexes are represented by the general formula 99mTcN(L)2, where L is the monoanionic form of a dithiocarbamate ligand of the type [R1(R2)-N-C(=S)S]-, and R1 and R2 are variable, lateral groups. The preparations were carried out, both as a liquid and freeze-dried formulation, through a simple procedure involving the initial reaction of [99mTcO4]- with S-methyl N-methyl dithiocarbazate [H2NN(CH3)C(=S)SCH3], in the presence of tertiary phosphines or Sn2+ ion as reductants, followed by the addition of the sodium salt of the ligand (NaL) to afford the final product. The chemical identity of the resulting complexes was determined by comparing their chromatographic properties with those of the corresponding 99Tc analogs characterized by spectroscopic and x-ray crystallographic methods. The complexes are neutral and possess a distorted, square pyramidal geometry. RESULTS: No decomposition of the complexes, in physiological solution, was observed over a period of 6 hr. Imaging and biodistribution studies demonstrated that these radiopharmaceuticals localize selectively in the myocardium of rats, dogs and primates, but that they failed to visualize the pig heart. The kinetics of heart uptake and clearance were studied in rats and dogs, and found to be strongly influenced by variation of the lateral R1 and R2 groups. CONCLUSION: The high quality of myocardial images obtained in dogs and monkeys demonstrates that the derivative 99mTcN[E-t(EtO)NCS2]2 [99mTcN(NOEt)] exhibits the most favorable distribution properties for further studies in humans.     

Clinico-morphological analysis of clinically unrecognized subdural hematomas

The authors report clinical and morphological analysis of 31 autopsied cases of subdural haematomas unrecognized during life. The most frequent erroneous clinical diagnosis was cerebrovascular brain disease, psychiatric syndrome or brain tumour. The greatest diagnostic difficulties were encountered in cases of subdural haematoma developing in elderly subjects (in this material 24 patients were aged above 60 years). Brain atrophy delayed in them the appearance of intracranial raised pressure syndrome, coexistence of vascular changes masked the signs of subdural haematoma and frequent memory disturbances made history taking difficult. Brain atrophy in elderly subjects may be also a factor contributing to development of subdural haematoma. Widening of subdural space causes greater tension of bridging veins and their easier rupture when the brain is displaced during trauma. Absence of inflammatory changes in the neuropathological findings in cases of subdural haemorrhage suggests that the term "chronic subdural haematoma" is better than the older term "pachymeningitis haemorrhagic interna".     

Retention of insoluble particles after local intrabronchial deposition in dogs

Recent studies have challenged the generally accepted hypothesis that bronchial particle clearance is complete within 24-48 h postdeposition. We studied bronchial retention of inert particles using a bronchoscope and microspray nozzle to localize deposition in a bronchus while avoiding alveolar deposition. Six-microliter aliquots (444 kBq) of submicrometer (number mean diameter = 0.22 microns, geometric standard deviation = 1.75) technetium-99m-labeled (99mTc) sulfur colloid (SC) particles (n = 6) or the unbound radiolabel 99mTc-pertechnetate (99mTcO4-; n = 3) were sprayed onto a 5-mm-diam bronchus in halothane-anesthetized dogs. Radioactivity at the deposition site and clearance pathway was monitored externally with a gamma camera beginning immediately postspray. Bronchial retention of SC was 8.5 +/- 2.4 and 1.5 +/- 0.7% at 3 and 24 h postspray, respectively. Tracheal mucus velocity was measured at 10.4 +/- 2.2 mm/min. For comparison, clearance of inhaled submicrometer SC particles was also measured in the same dogs. Retention of inhaled aerosolized SC (peripheral lung deposition) was 98.1 +/- 1.1 and 76.3 +/- 1.8% at 3 and 24 h, respectively. 99mTcO4- cleared from the bronchi slightly more rapidly than did SC. Radioactivity was readily detected in the blood after deposition of 99mTcO4- but not of SC. Thus SC cleared by mucociliary transport, whereas 99mTcO4- cleared predominantly by transepithelial absorption. We conclude that clearance of submicrometer particles from a 5-mm conducting airway is very nearly complete by 24 h, with approximately 92% of the clearance occurring within the first 3 h postdeposition.     

Solitary giant skull base schwannomas--report of four cases

BACKGROUND: Solitary intracranial schwannomas not related to major nerves or neurofibromatosis as well as paranasal schwannomas are rare. Schwannomas simultaneously involving the paranasal sinuses and intracranial cavity are even rarer. METHODS: We report four cases of schwannomas simultaneously involving the intracranial cavity and paranasal sinuses. They were successfully managed by surgery. The literature on such tumors is reviewed. RESULTS: All patients were young adults; the male to female ratio was 1:3. In two patients, the tumor was predominantly intracranial with extension into the sphenoid and ethmoid sinuses, whereas in the other patients, the tumor was located predominantly in the paranasal sinuses and nasopharynx with intracranial extension. Radiologically, bone destruction was seen in three cases. The tumors were totally removed piecemeal with repair of the basal dura. Histopathologic examination confirmed the diagnosis of schwannoma in all four cases. Three patients are alive and well; one of them was reoperated for a recurrence. CONCLUSIONS: These tumors should be excised completely if possible. Radiologically, bone erosion or destruction are suggestive of malignancy but histopathology clinches the diagnosis. Therefore, drastic surgery should be avoided in these cases. Surgery is generally curative in these massive schwannomas.     

Intracranial hemorrhage associated with idiopathic thrombocytopenic purpura: report of seven patients and a meta-analysis

We present the results of a meta-analysis using clinical data obtained from seven of our patients and 24 previously reported patients with idiopathic thrombocytopenic purpura complicated by intracranial hemorrhage. Twenty-four had an intracerebral hemorrhage (ICH) and seven had a subdural hematoma (SDH). Mean age of the patients with ICH was significantly younger than those with SDH. The mortality rate of ICH associated with ITP was similar to that of spontaneous ICH. All seven patients with SDH improved without sequelae.     

Anterior communicating artery aneurysm rupture: an unusual cause of acute subdural hemorrhage

A case of acute subdural hemorrhage caused by rupture of an anterior communicating artery aneurysm is presented. The patient is a young man who presented with an acute onset of neurologic symptoms; computed tomography revealed subdural hemorrhage in the absence of associated subarachnoid or intraparenchymal bleeding.     

Subdural tension pneumocephalus following head injury: report of five cases

Intracranial air is a radiographic finding not uncommon in head-injured patients. It is a relatively benign complication which usually resolves spontaneously. However, under unclear mechanism, tension pneumocephalus (the entrapment of intracranial air under pressure) may be formed and cause neurological symptoms. Five cases of patients with subdural tension pneumocephalus following head injury were reported. All had a basal skull fracture involving the paranasal sinuses or mastoid air cells with coexisting cerebrospinal fluid leakage. The patients showed symptoms and signs of increased intracranial pressure and compression on frontal lobes. Characteristic computerized tomographic findings were noted. Four patients clinically improved with conservative strategy. Only 1 case needed operative correction.     

The Mark IV system for radionuclide computed tomography of the brain

The Mark IV scanning system is a simple four-sided arrangement of 32 independent detectors which rotate continously as a unit, detecting, processing, and displaying the reconstructed data while the study progresses. Detection is by single photon counting and is compatible with commercially available radionuclides. An empirical correction is applied for attenuation, difference in detector response, and scatter. It is a high-sensitivity device with approximately uniform resolution throughout the section plane. There is good reproducibility and accuracy for absolute quantification of radionuclide concentration in the brain. Clinical applications include scans of 99mTcO4, 99mTc-RBC, 123I-iodoantipyrine, 99mTc-diphosphonate, and 111In-DTPA.     

Distribution of glutathione and technetium-99m-meso-HMPAO in normal and diethyl maleate-treated mouse brain mitochondria

The aim of this study was to explain the contribution of mitochondria to the accumulation of 99mTc-meso-hexamethyl propyleneamine oxime (HMPAO) in the brain, after examinations were performed. METHODS: We studied subcellular distribution of 99mTc-meso-HMPAO and glutathione (GSH) in normal and diethyl maleate (DEM)-administered mice. RESULTS: In normal brain, major radioactivity was found in the mitochondrial (49.0%) and cytosolic fractions (33.0%), while the GSH content was high in the cytosol (63.2%) and mitochondria (30.6%). The radioactivity in mitochondrial, cytosolic, microsomal and nuclear fractions was decreased in a dose-dependent manner by DEM, a GSH depleting agent, to 32.2% (mitochondrial) and 24.7% (cytosolic) of the control by a dose of 550 mg/kg. The GSH content in mitochondrial and cytosolic fractions also decreased in a dose-dependent manner on DEM treatment to 29.3% (mitochondrial) and 30.0% (cytosolic) of the control by 550 mg/kg of DEM. A good correlation was found between the uptake of 99mTc-meso-HMPAO and GSH content in mitochondrial, cytosolic and nuclear fractions, with a correlation coefficient (r) of 0.814, 0.834 and 0.784, respectively. CONCLUSION: Mitochondria are a major subcellular fraction for the uptake of 99mTc-meso-HMPAO by the brain, and GSH in mitochondria contributes to the accumulation of 99mTc-meso-HMPAO.     

Normal brain perfusion pattern of technetium-99m-ethylcysteinate dimer in children

The purpose of this study was to assess the normal perfusion pattern of the pediatric brain with 99mTc-ethylcysteinate dimer (99mTc-ECD). METHODS: Tomographic imaging was performed with a dedicated system with high sensitivity and resolution. Sixteen children, referred for brain imaging in the workup of seizure disorder, were included since they turned out negative after a 1-yr follow-up. A standardized brain presentation was obtained after reslicing and reorienting of the three-dimensional volumetric dataset. RESULTS: Quantitative analysis did not reveal significant left-right uptake differences per patient. Three age clusters were investigated that showed differences in regional uptake, mainly a relatively increased uptake in basal ganglia, visual and motor cortex. An uptake ratio or perfusion index was calculated after normalization. Normal limits were established for the children in the three groups. CONCLUSION: Technetium-99m-ECD is a safe agent for children and should be the radiopharmaceutical of choice for brain perfusion studies because of favorable radiation dosimetry and stability. The age dependence of perfusion necessitates a database comparison before concluding that the observed perfusion pattern is normal.     

Reversible amnesia associated with a left temporal hematoma in a case of right temporal complex partial seizures

We report the case of a 44-year-old woman with complex partial seizures (CPS) of right frontotemporal origin who developed generalized amnesia after undergoing intracranial electrode implantation complicated by left hippocampal hemorrhage. Serial memory testing disclosed recovery from the amnesic disorder, while repeated magnetic resonance imaging (MRI) showed resolution of her left hippocampal hemorrhage in a 2-month period. A second intracarotid amytal procedure confirmed the capability of her left temporal region to support memory. Consequently, a right orbitofrontotemporal lobectomy was performed without complication.