Anterior circulation aneurysms: surgical perspectives

Aneurysms arising from the internal carotid circulation represent 85% of all intracranial aneurysms. The intimate relationship of the internal carotid artery and its branches with the brain and cranial nerves, and the distribution of the internal carotid artery flow, make these aneurysms challenging, and potentially complicated in their surgical management. Great attention to detail, and clear understanding of the operative anatomy of the carotid system, facilitate the safe and successful treatment of these aneurysms. The surgical experience with 475 anterior circulation aneurysms treated from 1980 to 1992 is presented. The aneurysms arose from the internal carotid artery: 230(40%), middle cerebral artery: 152(32%), and anterior cerebral artery: 133(28%). Of aneurysms arising from the internal carotid artery, there were 142(30%) from the posterior communicating artery; internal carotid bifurcation: 29(6%), and anterior choroidal artery: 19(4%). There were 62(13%) giant aneurysms evenly distributed among the middle cerebral, internal carotid bifurcation and anterior cerebral artery. Serious neurological morbidity was observed in 13(3%) patients, who presented a combination of different neurological symptoms including: hemiplegia 3, hemiparesis 6, dysphasia 7, and loss of vision 4. Two patients developed a myocardial infarct and survived. Mortality occurred in 16(3%); these patients died from: a hemispheric infarction 7, severe vasospasm 6, myocardial infarction 2, and pulmonary emboli 1. All aneurysms appeared angiographically obliterated. Vasospasm was observed in 75(16%) patients of which nine were symptomatic, and six of them died. Six major arterial trunks were occluded in the post-operative angiogram, and three patients had occlusion of the internal carotid artery, not identified during surgery. Three of these patients with unexpected occlusions died from a major cerebral infarction, and three had lasting hemipareses and dysphasia. Surgical correction of internal carotid aneurysms can be conducted safely when the anatomical characteristics of the intracranial vessels is preserved, and when these patients are treated with appropriate medical support.     

The effect of hypoprolactinemia alone and in combination with cyclosporine on allograft rejection

Recent evidence suggests that prolactin has a role in regulating immune function. Hypophysectomy or administration of bromocriptine results in suppression of the immune response, which is reversed by the administration of prolactin. Hypoprolactinemia has been shown to augment the immunosuppressive effect of cyclosporine. We studied the effect of hypoprolactinemia induced by a new drug, CQP 201-403, on the survival of heterotopic cardiac allografts in the rat and the ability of peripheral blood lymphocytes to respond in vitro to plant mitogens. CQP treatment alone produced a small increase in graft survival but no change in lymphocyte in vitro proliferation (P less than 0.05). CQP treatment greatly enhanced the immunosuppressive effect of cyclosporine on graft rejection and in vitro lymphocyte function (P less than 0.02). We conclude that modulation of prolactin may be a useful adjunct to cyclosporine immunosuppression.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Assembly of contact-phase factors on the surface of the human neutrophil membrane

H-kininogen (HK), a major factor involved in contact-phase activation, was recently immunolocalized on the external surface of human neutrophils. Experiments were, therefore, designed to consider the question of whether the complete assembly of contact factors occurs on the outer surface of the neutrophil membrane. By immunolocalization techniques, and using specific antibodies directed against the various contact factors, we now demonstrate that plasma prekallikrein (PK), factor XI (FXI), and factor XII (FXII) are present on the exterior face of the human neutrophil. Failure to localize HK, PK, or FXI by monoclonal antibodies directed to their reciprocal binding sites, and displacement of PK/FXI by peptide HK31, which mimics the relevant binding site(s) of HK, suggested that prekallikrein and FXI are anchored to the neutrophil membrane through attachment to the kininogen molecule. Probing of the kinin moiety by a specific antibody showed that kininogen molecules bound to the neutrophil cell membrane contain the kinin sequence, which can be released by plasma kallikrein or by tissue kallikrein. Our results led us to the novel conclusion that neutrophils provide a circulating platform for the components of the contact-phase system.     

Purified murine hematopoietic stem cells function longer on nonirradiated W41/Wv than on +/+ irradiated stroma

Mouse bone marrow (BM) was separated into low-density, lineage- negative, wheat germ agglutinin-positive (WGA+), Rhodamine-123 bright (Rhbright) or dim (Rhdim) cells to obtain populations that were highly enriched for committed progenitors (Rhbright cells) or for more primitive stem cells (Rhdim). When 2,500 Rhbright or Rhdim cells were seeded onto 6-week-old irradiated (20 Gy) long-term BM cultures (LTBMC), the nonadherent cell production from Rhbright cells was transient and ended after 5 weeks. Production from Rhdim cells did not begin until week 3, peaked at week 5, and ended at week 8, when the irradiated stroma seemed to fail. Termination of cell production from Rhdim cells did not occur in nonirradiated LTBMC from W41/Wv mice. During peak nonadherent cell production, 25% to 30% of the cells in the nonirradiated LTBMC from W41/Wv mice had donor cell markers. Two approaches were tested to try to enhance the proportion or number of donor cells. Addition of Origen-HGF at the time of seeding Rhdim cells caused a nonspecific increase in both host and donor cell production, but a specific increase in production of donor cells was obtained by seeding the cultures at 2 weeks rather than 6 weeks. Limiting dilution of Rhdim cells gave the same frequency of wells producing cells on both irradiated +/+ and nonirradiated W41/Wv or W/Wv cultures.     

[11C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

The PET tracer [¹¹C]5-hydroxytryptophan ([¹¹C]5-HTP), which is converted to [¹¹C]5-hydroxytryptamine ([¹¹C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [¹¹C]5-HTP in rat? Male rats were scanned with [¹¹C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [¹¹C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [¹¹C]5-HTP uptake, and the k₃. This was unexpected as NSD 1015 directly inhibits the enzyme converting [¹¹C]5-HTP to [¹¹C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [¹¹C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.