Pituitary abnormalities in eating disorders: further evidence from MRI studies

1. The frequent occurrence of hypothalamo-pituitary dysfunction in patients with eating disorders as well as prior reports that nutritional and endocrine status influence pituitary morphology, led us to hypothesize that pituitary size and shape may be altered in patients with eating disorders. 2. Magnetic resonance imaging (MRI) does not use ionizing radiation and is currently one of the most feasible modalities available to study the pituitary gland in vivo. Using MRI, we have previously reported in a preliminary study that female patients with eating disorders had significantly smaller pituitary glands than controls. In addition MRI excluded any pituitary mass lesions. 3. In this report, we confirm our previous MRI findings and provide further evidence of pituitary abnormalities in an expanded sample of eating disorder patients. Preliminary data on pituitary volume estimates from MRI scans are provided for a subset of patients and controls.     

Selective anorexigenic effects of corticotropin releasing hormone in the rhesus monkey

1. Rhesus monkeys were equipped with a novel intracerebroventricular (i.c.v.) cannula system and trained to respond under operant schedules of food presentation or termination of stimuli associated with the delivery of shock (escape). 2. CRH decreased food-maintained behavior in a dose-related manner over the range of (0.3-10 micrograms/kg) but did not affect escape responding, demonstrating a selective effect on food-maintained responding. 3. This selective effect was related to the tendency for responding to stop after delivery of a food pellet when higher doses of CRH were given, consistent with the notion that a conditioned aversion to food was established in the presence of CRH. 4. This may suggest that in hyperaroused clinical states such as depression and anorexia nervosa, focus is shifted away from appetitive tasks as a result of increased levels of CRH.     

Herpes simplex virus latency in the nervous system – a new model

Permissive herpes simplex virus (HSV) infection in tissue culture results in host cell destruction. Latent HSV infection in vivo occurs in neurons of peripheral sensory ganglia (PSG) and it therefore can not take place in neurons in which the virus has completed a lytic replication cycle similar to that present in vitro. Our hypothesis, based on experimental data and observations in humans, suggests that establishment of latent infection and reactivation of HSV-1 does not involve neuronal cell loss. Latency is established in neurons in which the virus does not replicate and is determined, in part, by the tissue levels of a herpes transactivating protein (Vmw65) that is a component of the viral tegument. We also suggest that reactivation of latent infection does not involve destruction of neurons and is due to replication of virus at the peripheral mucocutaneous tissues to where virus or viral DNA have been transported from the nervous tissue. Alternatively, reactivation is initiated in the PSG using a replication cycle which does not involve irreversible damage to neurons. This model explains the lack of damage to neurons which continue to serve as permanent reservoirs of latent virus for the entire life of the host.     

Primary and secondary lymphomas of the brain: an MRI study

Three types of lymphoma of the central nervous system are known: primary non-Hodgkin's malignant lymphoma (NHML), secondary NHML and neurological lesions of Hodgkin's disease. NHML's are rare tumours, often associated with immunodeficiency and presenting predominantly as neuropsychological disorders. In this study 8 patients were explored by CT and MRI, with pathological confirmation. None of our patients had AIDS. The most typical neuroradiological image of this type of tumour is that of a large and intensely contrast-enhanced tumoral mass which is often multifocal and periventricular with infiltration of the subarachnoidal spaces and leptomeninges. Mass effect and perifocal oedema are less pronounced than expected with tumours of that size. NHML's may totally regress under corticosteroid therapy. This tumour of obscure aetiology must be recognized as it is now increasingly frequent.     

Haemangioma of the maxillary antrum

Haemangioma of the maxillary sinus is rare. Clinical diagnosis is of utmost importance for its operative treatment and prevention of hazards. A case is reported for its rarity and some unusual features.     

Carcinoembryonic antigen expression of resurgent human colon carcinoma after treatment with therapeutic doses of 90Y-alpha-carcinoembryonic antigen monoclonal antibody

We have previously shown that the colon carcinoma (LS174T) xenografts that emerged shortly after radioimmunotherapy with 90Y-labeled anti-CEA monoclonal antibody (MAb) ZCE025 lacked significant expression of CEA in comparison with the untreated tumors. The present study was designed to establish if the immunophenotype of the treated tumors was the result of CEA specific therapy and if the effect was permanent. Athymic mice bearing LS174T tumors were treated either with 120 mu Ci of 90Y-ZCE025, an equal dose of 90Y-96.5 (nonspecific MAb), or received no treatment. When the treated tumors grew to approximately 1.5 cm in diameter (6 weeks after therapy), they were resected and aliquoted to be transplanted to other mice, plated in tissue culture, fixed in formalin, and homogenized for CEA quantitation. The procedure was repeated 3 times (a total of 4 months after treatment). The CEA content was evaluated 2 and 6 weeks after therapy and when the tumors were transplanted. We confirmed a 4-fold decrease of CEA in the resurgent tumors 6 weeks after specific 90Y-ZCE025 therapy, which was twice the decrease experienced by the tumors treated with nonspecific 90Y-96.5, indicating substantial and specific killing of CEA-expressing cells. The CEA content slowly but progressively increased with each new pass of the tumor in the mice, reaching approximately one-half the value of the controls at the end of the study. The resurgent tumors were also studied by immunohistochemistry with MAbs detecting different epitopes of CEA, keratin, TAG-72, and epithelial membrane antigen to evaluate possible additional immunophenotypic changes induced by radioimmunotherapy. Only the expression of TAG-72 (recognized by MAb B72.3) increased immediately after therapy, but it returned to the original levels by the end of the study. These results suggest that: (a) specific radioimmunotherapy with 90Y-ZCE025 selectively kills cells that express higher levels of CEA; (b) the immunophenotype of the surviving fraction of the tumor appears to slowly revert to its original form; and (c) other tumor markers unrelated to CEA can also be affected. These observations have important implications for the design of radioimmunotherapy trials.     

Cerebrovascular and metabolic perturbations in delayed heavy charged particle radiation injury

Focal heavy charged particle irradiation of the rabbit brain created defined lesions which were observable by nuclear magnetic resonance (NMR) and positron emission tomography (PET) imaging techniques. The lesions appeared approximately 9-11 months after left partial hemibrain irradiation with 30 Gy (230 MeV/u helium ions), and were restricted to the white matter tracts and deep perithalamic and thalamic regions. 82Rubidium PET and Gadolinium DTPA enhanced NMR imaging were used to detect blood-brain barrier perturbations. 18Fluordeoxyglucose PET studies demonstrated widespread decreases in cerebral glucose uptake in the cortex and thalamus of the irradiated hemisphere. NMR and PET imaging results correlated well with histological findings. Rabbits irradiated with 15 Gy did not demonstrate any abnormalities in the brain with sequential NMR scans through 14 months post-irradiation.