Saturation analysis of specific 11C Ro 15-1788 binding to the human neocortex using positron emission tomography

The ¹¹C-labelled benzodiazepine antagonist Ro 15–1788 (flumazenil) and positron emission tomography (PET) were used to determine quantitative characteristics of benzodiazepine receptor binding in the neocortex of healthy young men. Saturating doses of unlabelled flumazenil administered i.v., before or together with the ligand-reduced ¹¹C-flumazenil accumulation in the neocortex by about 90 per cent. Saturating doses of unlabelled flumazenil had little effect on the accumulation of radioactivity in the benzodiazepine receptor-poor regions such as pons or white matter. By giving graded doses of unlabelled flumazenil together with the tracer, saturation isotherms were obtained allowing the calculation of receptor density (B_max) and equilibrium dissociation constant (K_d) values on the basis of certain assumptions B_max values were in the order of 90 pmol/g and K_d values in the order of 10 nM in the neocortex. Scatchard and Hill plots of the radioactivity data indicated that ¹¹C-flumazenil binds to saturable sites of a homogeneous population. The data indicate that intravenous doses of 1 or 2 mg flumazenil result in a benzodiazepine receptor occupancy of about 50 per cent. The method described should be useful for studying regional differences in benzodiazepine receptor characteristics in the living human brain in healthy subjects and neuropsychiatric disorders, and also in relation to treatment with drugs interacting with benzodiazepine receptors.     

Repetitive, negligible force reaching in rats induces pathological overloading of upper extremity bones.

Work-related repetitive motion disorders are costly. Immunohistochemical changes in bones resulting from repetitive reaching and grasping in 17 rats were examined. After 3-6 weeks, numbers of ED1+ macrophages and osteoclasts increased at periosteal surfaces of sites of muscle and interosseous membrane attachment and metaphyses of reach and nonreach forelimbs. These findings indicate pathological overloading leading to inflammation and subsequent bone resorption. INTRODUCTION: Sixty-five percent of all occupational illnesses in U.S. private industry are attributed to musculoskeletal disorders arising from the performance of repeated motion, yet the precise mechanisms of tissue pathophysiology have yet to be determined for work-related musculoskeletal disorders. This study investigates changes in upper extremity bone tissues resulting from performance of a voluntary highly repetitive, negligible force reaching and grasping task in rats. MATERIALS AND METHODS: Seventeen rats reached an average of 8.3 times/minute for 45-mg food pellets for 2 h/day, 3 days/week for up to 12 weeks. Seven rats served as normal or trained controls. Radius, ulna, humerus, and scapula were collected bilaterally as follows: radius and ulna at 0, 3, 4, 5, 6, and 12 weeks and humerus and scapula at 0, 4, and 6 weeks. Bones were examined for ED1-immunoreactive mononuclear cells and osteoclasts. Double-labeling immunohistochemistry was performed for ED1 (monocyte/macrophage lineage cell marker) and TRACP (osteoclast marker) to confirm that ED1+ multinucleated cells were osteoclasts. Differences in the number of ED1+ cells over time were analyzed by ANOVA. RESULTS: Between 3 and 6 weeks of task performance, the number of ED1+ mononuclear cells and osteoclasts increased significantly at the periosteal surfaces of the distal radius and ulna of the reach and nonreach limbs compared with control rats. These cells also increased at periosteal surfaces of humerus and scapula of both forelimbs by 4-6 weeks. These cellular increases were greatest at muscle attachments and metaphyseal regions, but they were also present at some interosseous membrane attachments. The number of ED1+ cells decreased to control levels in radius and ulna by 12 weeks. CONCLUSIONS: Increases in ED1+ mononuclear cells and osteoclasts indicate that highly repetitive, negligible force reaching causes pathological overloading of bone leading to inflammation and osteolysis of periosteal bone tissues.     

Comorbidities of migraine: a user-friendly overview

Comorbidity of migraine is important from a number of different perspectives. Co-occurrence of different diseases may complicate diagnosis as a high degree of symptomatic overlap may occur among conditions associated with migraine. Furthermore, comorbidity has also important implications for treatment. The commonest comorbidities of migraine are represented by psychiatric disorders, epilepsy, tremor, stroke, and cardiovascular abnormalities.     

Complete hepatic venous isolation and extracorporeal chemofiltration as treatment for human hepatocellular carcinoma: A phase I study

Background: We performed a phase I study of a novel system of complete hepatic venous isolation and extracorporeal chemofiltration in patients with unresectable hepatocellular carcinoma (HCC) to determine (a) whether systemic exposure to doxorubicin could be limited after high-dose hepatic arterial infusion (HAI), and (b) the hepatic maximum tolerated dose (MTD) of doxorubicin. Methods: Ten patients with biopsy-proven HCC were treated with 20-min HAI of doxorubicin (17 total treatments). Two patients were treated with doxorubicin 60 mg/m², three patients were treated at 90 mg/m², and five patients received 120 mg/m². A newly developed dual-balloon vena cava catheter was advanced from the femoral vein, and the balloons were inflated to isolate and capture total hepatic venous outflow. The hepatic venous blood was pumped through extracorporeal carbon chemofilters before return of the blood to the systemic circulation. Results: Peak systemic doxorubicin levels were an average 85.6% lower than were peak prefilter levels (p<0.01). Because all catheters were placed percutaneously and because the chemofiltration markedly limited systemic chemotherapy exposure, patients were discharged 1 day after 16 of the 17 treatments. The hepatic and systemic MTD of doxorubicin in this treatment protocol was 120 mg/m². Conclusions: This novel system of complete hepatic venous isolation and chemofiltration limits systemic chemotherapy toxicity and will allow use of higher doses of chemotherapeutic agents to treat HCC. The results of this study were presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

The role of surgery in the management of unusual complications of transcatheter arterial embolization for hepatocellular carcinoma

Transcatheter arterial embolization (TAE) is accepted to be an effective treatment in both resectable and nonresectable hepatoma, which is very prevalent in Taiwan. Two hundred and twenty-five embolizations of TAE were performed in 137 patients in a 3-year period. Postembolization syndrome developed in the majority of patients. We analyzed these patients to study the nature and incidence of unusual complications and the surgical role in their managment. In our series, unusual complications, which were rarely reported in the literature, included 13 cases (5.8%) of gastroduodenal bleeding, 2 cases (0.9%) of duodenal perforation, 9 cases (4.0%) of acute pancreatitis with 1 case of gangrenous change, 24 cases (10.7%) of gallbladder infarction with 1 case of perforation, 4 cases (1.8%) of delayed formation of gallstones, 3 cases (1.3%) of hyperuricemia, and 2 cases (0.9%) of hepatoma rupture. Ischemic necrosis of the organs may be attributed to the inadvertent blockade of the gastroduodenal artery, gastric artery, cystic artery, and important collaterals. Inadequate superselectivity, the size of the tumor, regurgitation of embolus, anatomical variations, injury of vessel intima, or pseudoaneurysm formation resulting from previous embolization attempts made the avoidance of complications difficult with this technique. Most of the unusual complications could be managed by conservative treatment, but urgent operation was indicated in the cases of organ perforation. Elective operation was also needed for the delayed formation of gallstones with prominent symptoms. Awareness of the occurrence of these untoward sequelae makes us more careful in the evaluation and long-term follow-up of patients following TAE. Surgical intervention plays a selective but important role in the management of these unusual complications.

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Resumen La embolización arterial por cateterismo (EAC) es aceptada como tratamiento efectivo tanto en los hepatomas resecables como en los no resecables, tumores de alta incidencia en Taiwan. Doscientos veinticinco embolizaciones por EAC fueron realizadas en 137 pacientes en un período de 3 años; el síndrome de postembolización se desarrolló en la mayoría de los pacientes. Hemos analizado estos pacientes para estudiar la naturaleza y la incidencia de las complicaciones poco usuales y el papel de la cirugía en su manejo. Las complicaciones poco usuales observadas en nuestra serie, las cuales son raramente informadas en la literatura, incluyen 13 casos (5.8%) de hemorragia gastroduodenal, 2 casos (0.9%) de perforación duodenal, 9 casos (4.0%) de pancreatitis aguda con 1 caso de necrosis gangrenosa, 24 casos (10.7%) de infarto de la vesícula biliar con 1 caso de perforación, 4 casos (1.8%) de formación tardía de cálculos, 3 casos (1.3%) de hiperuricemia, y 2 casos (0.9%) de ruptura del hepatoma. La necrosis isquémica de los órganos puede ser atribuida a la oclusión inadvertida de la arteria gastroduodenal, la arteria gástrica, la arteria cística, y colaterales importantes. Superselectividad inadecuada, tamaño del tumor, regurgitación del émbolo, variaciones anatómicas, lesión de la íntima de la pared vascular, o formación de pseudoaneurismas como consecuencia de intentos previos de embolización hicieron difícil evitar las complicaciones con esta técnica. La mayoría de estas complicaciones poco usuales pudieron ser manejadas con tratamiento conservador, pero la operación de urgencia fue necesaria en casos de perforación de un órgano. La operación electiva también fue necesaria en los casos con formación tardía de cálculos biliares y síntomas prominentes. La toma de conciencia sobre la posibilidad de este tipo de secuelas nos ha hecho aún más cuidadosos en la evaluación y el seguimiento a largo plazo de los pacientes sometidos a EAC. La intervención quirúrgica juega un papel selectivo pero importante en el manejo de estas complicaciones poco usuales.

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Résumé L'embolisation par cathétérisme artériel occupe à Taiwan une place fiable dans le traitement de l'hépatome opérable ou de l'hépatome inopérable. Au cours d'une période de 3 ans 225 embolisations intra-artérielle ont été pratiquées chez 137 malades. Dans la majorité des cas l'embolisation a entrainé des phénomènes secondaires anormaux. Les auteurs font état de complications inhabituelles qui ont été rarement relatées dans la littérature: 13 cas (5.8%) d'hémorragie gastro-duodénale, 2 cas (0.9%) de perforation duodénale, 9 cas (4.0%) de pancréatite aigue dont une avec altérations gangréneuses, 24 cas (10.7%) d'infarcissement de la vésicule dont un avec perforation, 4 cas (1.8%) de formation retardée de calculs vésiculaires, 3 cas (1.3%) d'hyperuricémie, 2 cas (0.9%) de rupture de l'hématome. La nécrose ischémique des organes peut être attribuée à l'obstruction imprévue de l'artère gastro-duodénale, de l'artère gastrique, de l'artère cystique, et d'importantes collatérales. De multiples facteurs peuvent être invoqués pour expliquer les complications indésirables de l'embolisation: cathétérisme hypersélectif inadéquat, volume de la tumeur, régurgitation de l'embolus, blessure de l'intima artérielle, formation pseudoanévrysmale résultant de tentatives antérieures de cathétérisme artériel. La majorité d'entre elles peuvent être traitées médicalement mais l'intervention d'urgence s'impose quand une perforation viscérale est en cause. Il convient également de procéder à la cholécystectomie lorsque la lithiase vésiculaire entraîne des troubles importants. Connaître l'existence possible de ces accidents fâcheux doit rendre circonspect dans l'évaluation exacte de la valeur et le suivi à long terme de l'embolisation. De toute façon l'intervention chirurgicale est indispensable pour traiter certaines complications de l'embolisation.

     

The filter properties of the arterial beds of organs in rats.

The frequency properties of arterial beds in organs were studied by temporarily ligating the renal, the gastric, the splenic or the superior mesenteric arteries of rats. Blood-pressure waves of the tail arteries were recorded before and during the ligations, and were analysed by Fourier's transformation. Their frequency spectra have been found to change profiles following specific patterns with the ligations of different arteries. The results were significant with regard to the frequency selectivities of the organic arterial beds. Such frequency properties can be clearly explained when the circulation system is viewed as an electrical circuit network in which the organic arterial beds work as filters.     

Recent advances in the management of primary breast cancers.

The current concept of breast cancer treatment arises from Fisher's theory that operable breast cancer has distant micrometastasis at its very early stages. Since it is the presence of systemic diseases or micrometastasis that determines the final outcome, variation in local treatment would not affect survival. Fisher's theory led to a change in local treatment, from Halsted's radical mastectomy to breast-conserving therapy (BCT), and the introduction of adjuvant systemic treatment. As part of the job of surgery is replaced by radiation therapy in local control, the efficacy and side effects of radiation should be carefully monitored. The recently published results of 20-year follow-up in 2 important studies confirm that BCT achieves equal survival compared to mastectomy in women with early breast cancers, even after all causes of mortality have been considered. The introduction of sentinel lymph node biopsy has further decreased the adverse impact of breast cancer treatment on women. As variation in local control does not affect survival, more efforts are being put into developing adjuvant systemic treatment with curative intent. Adjuvant chemotherapy has been demonstrated to substantially affect the survival of women with early breast cancers. It is now apparent from numerous studies that adjuvant therapy improves survival in all subgroups of women with early breast cancer, although the absolute benefit varies depending on axillary lymph node status, tumor size, and other prognostic factors. This article reviews recent advances in the management of primary breast cancer, including: long-term follow-up after BCT; side effects of radiation therapy in BCT; post-mastectomy radiotherapy; sentinel node biopsy; adjuvant hormone therapy; and chemotherapy, including new strategies such as the incorporation of taxanes, dose-dense chemotherapy schedules, and the use of aromatase inhibitors in place of, or in addition to, tamoxifen.