The function of the hypothalamo-pituitary axis in brain dead patients

Summary In order to find out the function of the hypothalamo-pituitary axis in brain dead patients, pituitary and hypothalamic hormone concentrations were measured and several anterior pituitary releasing tests were carried out in 39 brain dead patients. In addition, cerebral blood flow measurements were simultaneously performed. In almost all cases, the blood concentration of pituitary and hypothalamic hormones were above the sensitivity of the assay. Anterior pituitary releasing tests indicated that efficient functions of the hypothalamus were severely suppressed, while the normal secretory mechanism of the anterior pituitary was partially preserved in brain dead patients. Histological changes of hypothalamic neurons varied from barely detectable ghost cells to nearly normal cells even in the same case. Although, the remaining circulation seemed not to be sufficient enough to maintain integrated hypothalamo-pituitary function, as shown by the examinations of cerebral blood flow, the presence of hypothalamic hormones in the systemic circulation suggests that these hormones were released and carried from the hypothalamus by minimal flow which is preserved even after the diagnosis of brain death.     

DNA methylation by N-nitrosomethylbenzylamine in target and non-target tissues of laboratory rodents. Comparison with carcinogenicity

Following oral or systemic (subcutaneous) administration to rats,N-nitroso -methylbenzylamine (NMBzA) causes a high incidence of oesophageal tumours. Methylation of DNA purines by a single oral dose of [14C-methyl]-NMBzA was most extensive in the oesophagus, followed by liver, forestomach and lung. After a single intravenous injection, alkylation levels were also highest in oesophageal DNA, followed by liver, lung and forestomach. These differences in the extent of alkylation were found to correlate with the autoradiographic distribution of tissue-bound 14C-radioactivity in in-situ preparations of the upper gastrointestinal tract following oral exposure to [14C-methyl]-NMBzA. In mice, systemic administration of NMBzA leads to the development of forestomach and lung tumours; in this species, DNA methylation after intraperitoneal injection of NMBzA is highest in liver, followed by lung and forestomach. Administration of [14C-methyl]-NMBzA to mice in the drinking-water led to very high concentrations of alkylated DNA bases in both oesophagus and forestomach. This finding is in good agreement with carcinogenicity studies, which showed 100% carcinoma incidence at these sites. Autoradiographic studies indicate that in rats and mice the metabolism of NMBzA in the oesophagus is largely restricted to the mucosa, whereas in lung, bioactivation occurs predominantly in the bronchial epithelium. In autoradiographs from liver, tissue-bound radioactivity showed a patchy distribution, with predominant reaction in the centrilobular region. In Mongolian gerbils, methylation of lung DNA by a similar subcutaneous dose of [14C-methyl]-NMBzA was greater than in rats and mice, whereas in the remaining tissues, levels of methylated purines were comparatively low. Chronic subcutaneous administration of NMBzA to gerbils caused no tumour within an observation period of two years.     

Hypopituitarism associated with transsphenoidal meningoencephalocele

A 12-year-old boy with growth hormone deficiency and partial diabetes insipidus resulting from transsphenoidal meningoencephalocele and with eye abnormalities is described. Fifteen other patients with transsphenoidal meningoencepalocele have been reported. Hypothalamic-pituitary dysfunctions were diagnosed by endocrinological studies in seven cases. It is important to recognize transsphenoidal meningoencephalocele as a cause of hypopituitarism, since some cases may have gone unrecognized. The association of hypothalamic-pituitary dysfunction and a midline craniocerebral anomaly has been reported in patients with cleft lip and/or palate, septo-optic dysplasia, the holoprosencephalies, and Kallmann syndrome. However, there was no evidence of transsphenoidal meningoencephalocele in these disorders and this may be a different form of midline craniocerebral and midfacial anomaly.     

Sphenoethmoidal meningoencephalocele associated with agenesis of corpus callosum and median cleft lip and palate. Case report.

A case of sphenoethmoidal meningoencephalocele associated with agenesis of the corpus callosum and median cleft lip and palate in a baby boy is reported. Two other cases have been reported previously presenting exactly the same findings. It is possible that these malformations constitute a distinct type of congenital anomaly.     

Magnetic resonance imaging of Chiari malformations.

The authors describe the features of magnetic resonance (MR) images of Chiari type I and II malformations and present four illustrative cases. Downward displacement of the posterior fossa was more pronounced with type II than type I. A variety of intracranial anomalies were associated with the Chiari type II malformation, whereas type I was mainly associated with syringomyelia and craniovertebral changes. MR imaging is useful in the diagnosis of intracranial anomalies and those situated at the craniovertebral junction, including Chiari malformations.     

Rathke cleft cysts: correlation of enhanced MR and surgical findings.

PURPOSETo describe the gadolinium-enhanced MR findings of Rathke cleft cyst correlate them with the surgical findings, and define those preoperative findings that differentiate this lesion from other sellar and juxtasellar tumors.METHODSWe studied 18 patients who were diagnosed as having Rathke cleft cyst pathologically. These patients were imaged with T1- and T2-weighted coronal and sagittal spin-echo sequences. Fifteen of these patients received gadopentetate dimeglumine.RESULTSIn eight patients, the cyst showed low intensity on T1-weighted images and high intensity on T2-weighted images. At surgery, the cyst fluid was cerebrospinal fluid-like or light brown in five patients, motor oil-like in one patient, and milky in two patients. In 10 patients, cysts showed isointensity to high intensity on T1-weighted images and had various intensity on T2-weighted images. All 10 contained milky fluid. In three patients the intensity of fluid was heterogeneous. A waxy nodule was found in two patients. The position of the normal pituitary gland confirmed by surgery in all cases coincided with enhancement on MR imaging. The variable position of the normal pituitary gland was clearly identified in the sagittal images. The cyst walls showed no enhancement by gadopentetate dimeglumine.CONCLUSIONSBecause Rathke cleft cysts show variable intensities on MR, the diagnosis is often difficult when based on MR signal intensity values alone. MR imaging with gadopentetate dimeglumine does assist in the diagnosis of Rathke cleft cysts. Diagnostic clues include the lack of cyst wall enhancement and displacement of the normal pituitary gland.     

Identification of interleukin-6 producing fibroblastoid cells in cerebrospinal fluid from patients with leukemic meningitis

Cytokine producing native cells in cerebrospinal fluid (CSF) have not been identified. So, we investigated the cytokine producing ability of floating cells in CSF from patients with leukemic meningitis. Morphologic study revealed that established cell lines were polygonal or elongated in shape and had an abundant and irregular branched cytoplasm. Immunocytochemical analysis demonstrated positive reactivity with monoclonal anti-fibroblast antibody only. Interleukin-6 (IL-6) was constitutively produced in vitro by these cell lines; both interleukin-1 and lipopolysaccharides significantly increased its synthesis. These findings imply that these fibroblastoid cells are floating in CSF of patients with leukemic meningitis and produce IL-6 in response to various inflammatory stimulations in vivo.     

Comparison of middle cerebral artery trunk occlusion by silicone cylinder embolization and by trapping

The authors produced occlusion of the middle cerebral artery (MCA) trunk in dogs by two methods: silicone cylinder embolization and trapping. Comparative analyses of the clinicopathological features in these models, extending from the acute to chronic stage, were performed. Within 24 hours after embolization, the brain exhibited swelling without macroscopic infarction. Microangiograms revealed impaired filling in the deep areas of the brain with midline shift. At 4 to 7 days after embolization, the animals showed major neurological deficits, evident deep cerebral infarction, and poorly perfused areas in the deep cerebrum with prominent midline shift. At 3 to 4 weeks after embolization, the neurological deficits improved and the affected regions showed cavities or localized lesions. Microangiograms demonstrated hypervascular areas with abnormal vessels in the affected cerebrum. On the other hand, trapping of the MCA trunk produced mild neurological deficits, although there was no evidence of macroscopic lesions or impairment of filling. This study shows that silicone cylinder embolization in the MCA trunk produces a reliable and reproducible deep cerebral infarction in dogs.