99mTc-gentamicin: Chemical and biological evaluation

^99mTc-Gentamicin complex, a new agent for renal studies, is prepared by the reduction of pertechnetate by stannous chloride. Organ distribution in rats and paper chromatography with Whatman 3MM paper [developed in n-butanol, acetic acid, and water (4:1:1)] were favored as analytical tools for determination of labeling parameters of ^99mTc-Gentamicin. A higher concentration of stannous ion is responsible for the formation of insoluble technetium species which concentrate in the liver. The mean kidney: liver ratio of 10.4:1 was obtained 1 h after injection. This confirms that scintigraphic delineation of kidneys is highly satisfactory.     

Pancreatic tumors in multiple endocrine neoplasia type 1: Clinical presentation and surgical treatment

Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-erm outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors. This strategy should be applied especially in patients with aggressive family histories to possibly reduce the risk of malignant tumor progression.

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Resumen Entre 33 individuos con tumores pancréaticos endocrinos como componente del síndrome de neoplasia endocrina múltiple tipo 1 (NEM-1), 19 pacientes (58%) tenían hipergastrinemia, 7 (21%) hiperinsulinismo y 7 (21%) lesiones clínicas no funcionantes. En la totalidad de los pacientes sometidos a cirugía pancreática fue hallado por lo menos un tumor, incluso en aquellos con examenes de localización negativos anteriores a la operación. Estos pacientes también albergaban tumores macroscópicos, así como numerosos microadenomas; con frecuencia las lesiones demostraron inmunocoloración con diferentes hormonas, principalmente polipéptido, insulina, glucagón y somatostatina. Se encontraron lesiones endocrinas duodenales en 4 de cada 5 pacientes investigados, las cuales colorearon con gastrina y anticuerpos a la somatostatina. Se practicó resección pancreática distal (principalmente resección subtotal) en 18 pacientes, eventualmente combinada con enucleación del tumor (cuando éste se hallaba ubicado en la cabeza del páncreas) o duodenectomía; solamente unos pocos pacientes fueron sometidos a simple enucleación del tumor o al procedimiento de Whipple. El resultado a largo plazo fue más favorable en los pacientes con hiperinsulinismo, puesto que sólo uno presentó recurrencia clínica. Los pacientes con hipergastrinemia exhibieron apenas una disminución transitoria de los valores de gastrina sérica luego de la cirugía pancreática. Cuarenta y siete por ciento del conjunto tuvo o desarrolló metástasis, en tanto que la extensión local del tumor se presentó en 57% de los casos con lesiones no funcionantes. Nueve pacientes murieron por progresión de la neoplasia en el curso del seguimiento. En acuerdo con sugerencias previas, se considero quo la cirugía está indicada en pacientes con NEM-1 e hiperinsulinismo, aún en los casos en que no se visualiza radiológicamente la lesión, pero que la indicación puede ser ampliada para incluir también pacientes con sólo marcadores bioquímicos, tales como niveles elevados de gastrina, indicativos de la presencia de tumores macroscópicos. Esta estrategia debe ser aplicada principalmente en aquellos pacientes con historia familiar agresiva, con lo cual tal vez se reduce el riesgo de progesión maligna del tumor.

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Résumé Parmi 33 patients ayant une tumeur pancréatique endocrine due à une néoplasie endocrine multiple de type 1 (MEN-1), 19 (58%) avaient une hypergastrinémie, 7 (21%) un hyperinsulinisme et 7 (21%) une lésion cliniquement muette. On a mis en évidence au minimum une grosse tumeur chez tous les patients, y compris chez ceux dont les examens préopératoires de dépistage tumoral étaient négatifs. Les patients étaient également porteurs de tumeurs macroscopiques et de nombreux microadénomes. Les lésions montraient souvent un immunomarquage positif pour de multiples hormones, principalement le polypeptide pancréatique, l'insuline, le glucagon et la somatostatine. Des lésions endocrines duodénales furent retrouvées chez 4 des 5 patients explorés; elles montraient un immunomarquage avec les anticorps angigastrine et anti-somatostatine. Une résection pancréatique distale, le plus souvent subtotale, a été réalisée chez 18 patients. Elle était éventuellement complétée par une énucléation tmorale de la tête ou par une duodénotomie. Peu de patients ont bénéficié d'une simple énucléation ou d'une intervention de Whipple. L'évolution postopératoire à long terme a été plus favorable en cas d'insulinome puisque seul un patient a eu une récidive clinique. Les patients atteints de gastrinome n'ont présenté que transitoirement une diminution des taux sériques de gastrine après la chirurgie pancréatique. Quarante sept pour cent de ces patients avaient ou ont développé des métastases contre 57% des patients porteurs de lésions sans traduction clinique. Neuf patients sont décédés en raison de l'extension tumorale au cours du suivi. Conformément à des suggestions antérieures, la chirurgie semble indiquée chez les patients atteints de MEN-1 avec hyperinsulinisme même si la radiologie ne visualise pas de lésion. Mais cette indication peut être élargie aux patients dont seuls les paramètres biologiques sont en faveur d'une grosse tumeur (dont l'hypergastrinémie). Cette stratégie pourrait convenir particulièrement aux patients ayant des antécédents familiaux importants; elle permettrait peut-être de réduire le risque d'extension tumorale.

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Presented at the International Association of Endocrine Surgeons in Stockholm, Sweden, August, 1991.     

Method for Dissection of Mesenteric Metastases in Mid-gut Carcinoid Tumors

With adequate medical management the midgut carcinoid tumor generally is an indolent malignancy associated with substantial life expectancy and appreciable life quality, even in the presence of liver metastases and significant tumor burden. Abdominal complications may occur in this entity of carcinoids owing to entrapment of intestines and encasement of mesenteric vessels by mesenteric metastases and associated marked mesenteric fibrosis. This may be the cause of abdominal pain, disabling diarrhea, weight loss to the extent of malnutrition, and eventually the risk of death with acute or chronic intestinal obstruction or intestinal gangrene. Operative removal of the mesentericointestinal lesion is often indicated to prevent or treat these complications but may be technically difficult when mesenteric metastases extend in the vicinity of major vessels in the mesenteric root. At laparotomy 56 patients with advanced midgut carcinoids underwent removal of the mesenteric tumor with a method for preserving the mesenteric vessels. This was feasible by mobilizing and releasing the right colon and mesenteric root from posterior adhesions, identifying the mesenteric artery below the pancreas, and free-dissecting this artery on the tumor capsule in the mobilized mesentery. Dissection was successful even with tumors initially judged inoperable unless tumor growth completely surrounded the mesenteric vessels or extended retroperitoneally. One patient was subjected to distal intestinal artery bypass. Symptom relief was been substantial and often of long duration after mesenteric tumor removal in patients who prior to surgery often had threatening intestinal ischemia. Patients with advanced midgut carcinoids may benefit markedly from dissectional removal of mesenteric tumors, which (conceivably better than conventional wedge resection) preserves the length of the remaining intestine.     

Neuroprotective and symptomatological action of memantine relevant for alzheimer’s disease — a unified glutamatergic hypothesis on the mechanism of action

The involvement of glutamate mediated neurotoxicity in the pathogenesis of Alzheimer's disease is finding increasingly more acceptance in the scientific community. Central to this hypothesis is the assumption that in particular glutamate receptors of the N-methyl-D-aspartate (NMDA) type are overactivated in a tonic rather than a phasic manner. Such continuous mild activation leads under chronic conditions to neuronal damage. Moreover, one should consider that impairment of plasticity (learning) may result not only from neuronal damage per se but also from continuous activation of NMDA receptors. To investigate this possibility we tested whether overactivation of NMDA receptors using either non-toxic doses/concentrations of a direct NMDA agonist or through an indirect approach--decrease in magnesium concentration--produces deficits in plasticity. In fact NMDA both in vivo (passive avoidance test) and in vitro (LTP in CA1 region) impaired learning and synaptic plasticity. Under these conditions memantine which is an uncompetitive NMDA receptor antagonist with features of "improved magnesium" (voltage dependence, affinity) attenuated the deficit. The more direct proof that memantine can act as a surrogate for magnesium was obtained in LTP experiments under low magnesium conditions. In this case as well, impaired LTP was restored in the presence of therapeutically relevant concentrations of memantine (1 microM). In vivo, doses leading to similar brain/serum levels produce neuroprotection in animal models relevant for neurodegeneration in Alzheimer's disease such as neurotoxicity produced by inflammation in the NBM or beta-amyloid injection to the hippocampus. Hence, we postulate that if in Alzheimer's disease overactivation of NMDA receptors occurs indeed, memantine would be expected to improve both symptoms (cognition) and slow down disease progression because it takes over the physiological function of magnesium.     

Comparison of randomized preemptive dexketoprofen trometamol or placebo tablets to prevent withdrawal movement caused by rocuronium injection

Rocuronium is a non-depolarizing neuromuscular blocking agent which is associated with injection pain and induces withdrawal movement of the injected hand or arm or generalized movements of the body after intravenous injection. The aim of this randomized study was to compare the efficacy of pretreatment with oral dexketoprofen trometamol (Arvelles^®; Group A) with placebo (Group P) without tourniquet to prevent the withdrawal response caused by rocuronium injection. The study cohort comprised 150 American Society of Anaesthesiologists class I–III patients aged 18–75 years who were scheduled to undergo elective surgery with general anesthesia. The patients response to rocuronium was graded using a 4-point scale [0 = no response; 1 = movement/withdrawal at the wrist only, 2 = movement/withdrawal involving the arm only (elbow/shoulder); 3 = generalized response]. The overall incidence of withdrawal movement after rocuronium injection was significantly lower in Group A (30.1 %) than in Group P (64.6 %) (p < 0.001). The incidence of score 0 withdrawal movements was higher in Group A (69.9 %) than in Group P (35.4 %), that of score 1 withdrawal movements was similar between groups (Group A 21.9 %; Group B 26.1 %) (p = 0.560) and that of score 2 withdrawal movements was lower in Group A (8.2 %) than in Group P (38.5 %) (p < 0.001). There were no score 3 withdrawal movements in either group (p > 0.05). These results demonstrate that the preemptive administration of dexketoprofen trometamol can attenuate the degree of withdrawal movements caused by the pain of the rocuronium injection.     

Patients’ experience of partial tooth loss and expectations to treatment: a qualitative study in Danish and Swedish patients

Knowledge of impairments, wishes and expectations is essential to make correct decisions regarding oral rehabilitation. The purpose of this study was to investigate discomforts, wishes and expectations in patients’ with partial edentulism before entering oral rehabilitation. In Copenhagen, Denmark, and Malmö, Sweden, respectively, 20 patients with partial edentulism seeking rehabilitation were interviewed in a semistructured qualitative manner. The interviews were transcribed and analysed yielding overall domains. Six themes appeared as overall domains: (i) experienced impairments, (ii) experienced social awareness, (iii) expectation to treatment, (iv) expectation to durability/survival, (v) coping strategies dealing with the tooth loss including explanations of the tooth loss and (vi) modifications to experienced impairment. The impairments were mostly experienced as problems in social settings. Most participants expressed a simple wish to function normally; a fixed solution was preferred. Many Danish participants accepted a removable solution whereas only few Swedish participants did so. The domains ‘coping strategies’ and ‘modifications’ were not part of the chosen topics of interest, indicating a high wish of the participants to explain their tooth loss and how they coped with it. In conclusion, a large degree of social impairment was found in the patient group along with several coping strategies. The impairments were modified by a number of factors indicating that highly individualised care and treatment is needed. A state of normality was described as the primary treatment wish with a higher acceptance of removable solutions in Denmark than in Sweden. For final decision‐making, surrounding factors seemed to influence the patients’ choices.     

Incremental value of live/real time three‐dimensional transesophageal echocardiography over the two‐dimensional technique in the assessment of a tuberculoma involving the left atrium and appendage

Intracardiac tuberculomas are extremely rare, and cardiac involvement in tuberculosis accounts for only 0.5% of extrapulmonary tuberculosis. We report for the first time incremental value of live/real time three‐dimensional transesophageal echocardiography over two‐dimensional transesophageal echocardiography in the assessment of a tuberculoma involving the left atrium and left atrial appendage.