Insulin-like growth factors and insulin-like growth factor-binding proteins in relation to disease status and incidence of hypoglycaemia in patients with a gastrointestinal stromal tumour.

OBJECTIVE: Patients with a gastrointestinal stromal tumour (GIST) suffering from non-islet cell tumour-induced hypoglycaemia (NICTH), being associated with increased plasma levels of pro-insulin-like growth factor (IGF)-IIE[68-88], have been reported occasionally. We studied the clinical relevance of pro-IGF-IIE[68-88] and other IGF-related proteins in GIST patients. PATIENTS AND METHODS: Twenty-four patients were included. Plasma samples were collected before 1 week and median 5 months after start of treatment with imatinib, and levels of IGF-I, total IGF-II, pro-IGF-IIE[68-88], insulin-like growth factor-binding protein (IGFBP)-2, -3 and -6 were determined. GIST specimens from 17 patients and tumour cyst fluid from two patients were analysed for IGF-II and IGFBP-2. RESULTS: Before treatment and/or during follow-up, 3 of 24 (13%) patients showed increased plasma levels of pro-IGF-IIE[68-88]. All three developed NICTH. Overall, patients with metastatic disease, elevated serum lactate dehydrogenase activity or total tumour size >12 cm had the highest pro-IGF-IIE[68-88] levels. Most patients had increased plasma IGFBP-2 levels and these levels were significantly higher in patients with progressive disease. (Pro-)IGF-II was expressed in 82% of GISTs and IGFBP-2 only in one case. CONCLUSION: We identified pro-IGF-IIE[68-88] as a marker that may be used in the surveillance of GIST.

Daily rat tibial growth in vivo following hypothalamic sex reversal with neonatal and pubertal treatments with gonadal steroids.

A striking sex-related difference in postpubertal growth and growth hormone (GH) secretory pattern in the rat has been described. Although this sexual dimorphism seems to be determined by the neonatal effects of gonadal steroids on the hypothalamus, peripubertal exposure to steroids also plays an important role. In order to study the real influence of the hypothalamic sex and/or peripubertal gonadal steroids, the growth pattern of female and male rats in response to neonatal and peripubertal sexual steroid treatments was studied using microknemometry, a technique that allows non-invasive daily measurements of rat tibial growth rate. Neonatal steroid environment in males was modified by castration on day 1, whereas in females it was changed by a single neonatal testosterone administration on day 5 followed by castration at 13 days of age. From the onset of puberty to adulthood, both female and male animals received testosterone or estrogens, respectively. Neonatal treatment alone, i.e. androgenization of female and castration of male rats, were only able to induce a partial reversal of the original sex-dependent growth pattern. Additional peripubertal treatments achieved a complete change in the sex-linked growth pattern. Consistent with the effects observed on growth, the pituitary GH concentration was significantly increased in females, and diminished in males, when they were treated both at the neonatal and peripubertal stages. However, only this latter group, whose growth was more seriously compromised, showed decreased plasma insulin-like growth factor-I (IGF-I) levels. In conclusion, a complete feminization of male tibial growth pattern or masculinization of female pattern can only be achieved by maintaining the new steroid environment from puberty to adulthood.

Giant ventral intradural extramedullary neuroma: case report

OBJECTIVE AND IMPORTANCE: We report an extremely rare, giant, ventrally located, intradural extramedullary neuroma in a 32-year-old woman. It extended from the foramen magnum to the level of the 10th thoracic vertebra. To our knowledge, this is the largest reported intraspinal neuroma. CLINICAL PRESENTATION: A mixed polyradicular and medullary lesion with symptoms and signs of raised intracranial pressure was observed on clinical presentation. Magnetic resonance imaging of the entire neuraxis was suggestive of a neuroma. Histological findings revealed characteristics of a classic neuroma. INTERVENTION: A complete surgical excision of the tumor was accomplished through an osteoplastic laminotomy from C1 to T10 with monitoring of the somatosensory evoked potentials. CONCLUSION: Even such a huge, ventrally located, intradural extramedullary tumor, as in this patient, can be completely removed with good results when a preoperative radiological and histological diagnosis is considered. With the help of new-generation magnetic resonance imaging scans, the intradural neural, vascular, and other structures can be clearly outlined. These tests also obviate the need for invasive diagnostic procedures such as myelography. We recommend an osteoplastic laminotomy instead of laminectomy to reduce the risk of postoperative spinal instability.

A massive intrathecal cefazoline overdose.

This case report describes the clinical course of a patient who inadvertently received a massive intrathecal cefazoline overdose through a lumbar drain, which had been placed after trans-sphenoidal surgery for a pituitary adenoma. She received high-dose barbiturate therapy and was monitored with electroencephalography (EEG), somatosensory evoked potentials (SSEP), brainstem auditory evoked potentials (BAEP) and transcranial Doppler ultrasound (TCD). No cerebrospinal fluid (CSF) exchange was performed, but CSF was drained continuously with daily CSF-cefazoline level monitoring. Despite the extremely toxic dose, the patient soon recovered completely.

Management of the difficult airway. A case of failed fiberoptic intubation.

BACKGROUND: Fiberoptic intubation is the current gold standard for the management of difficult intubation. Nevertheless, in rare circumstances even fiberoptic intubation fails. METHODS: We describe the case of a female patient suffering from neurofibromatosis Recklinghausen and a giant malignant schwannoma on the neck obstructing the pharynx and compromising respiration. Based on the clinical presentation and the MRI findings, difficulties in airway management were anticipated and fiberoptic intubation of the awake patient was planned. RESULTS: After localizing the vocal cords it was not possible to advance the tube into the trachea due to the severe deviation of the glottis. A decision was made to cancel any further fiberoptic intubation attempts and a conventional tracheotomy was performed under local anaesthesia without problems. CONCLUSION: This case illustrates that even awake fiberoptic intubation has its failure rate, due to inability to visualize the larynx, inability to advance the tube over the fiberscope (as in the present case), or inability to direct the tube towards the larynx. Due to the extreme deviation of the larynx other established techniques for difficult intubation were not deemed appropriate in this case. Therefore, weighing the risks and benefits, a decision was made to perform a tracheotomy under local anaesthesia.

[Intracerebral schwannoma in a child--case report]. / Intracerebrales Schwannom bei einem Kind. Ein Fallbericht.

A case of an intracerebral, intraparenchymatous schwannoma in an 8-year-old child is presented. Clinical, radiological and histological findings as well as possible etiologies are discussed.

[Apathy syndrome as a sequela of postoperative irradiation of brain tumors in children]. / Das Apathie-Syndrom als Folge einer postoperative Bestrahlung bei kindlichen Hirntumoren.

The somnolence syndrome is a postirradiation syndrome in children. It is to be found after cranial irradiation of chemotherapeutically treated children with ALL (acute lymphocytic leukaemia). Rarely, however, it is a radiation sequela of operated cerebral tumors. We report on such a case of somnolence syndrome, review the literature and discuss the diagnostic and therapeutic problems.

Intradural manifestation of rheumatoid arthritis causing spinal cord compression.

Rheumatoid arthritis as a cause of medullary compression due to subluxation of rheumatically diseased joints is very common. However, spinal cord compression by rheumatoid nodules is seen rarely, usually by extradural lesions. We describe two cases of intradural rheumatoid nodules causing spinal cord compression.

[Large epidermoid cyst of the posterior cranial fossa]. / Grosses Epidermoid in der hinteren Schädelgrube.

An extensive epidermoid cyst in the posterior fossa was diagnosed in a 59 year old male patient. The most valuable indicator for differential diagnosis was given by plain skull x-ray showing a peripheral zone of sclerosis as the leading x-ray sign of epidermoids. CT and MRI complemented the preoperative diagnostic measurements.

Cerebral manifestation of hydatid disease in a child.

The case of a 9-year-old-boy with a left frontal hydatid cyst is reported. The infection was transmitted by a dog, the final host and a companion of the child. Recovery without complications was accomplished after puncturing, systemic antihelminthic therapy using mebendazole and, finally, total removal of the cyst.

Computerized tomography in vascular malformations of the brain.

Computerized tomography scans of 166 patients - 99 cases with 117 aneurysms, and 67 cases with angiomatous malformations - were reviewed and correlated with angiographic and clinical findings. An intracranial hemorrhage was identified by CT scan in 103 patients, in 60 cases with aneurysms (17 only subarachnoid, 43 intracerebral), and in 43 cases with angiomas (6 only subarachnoid, 37 intracerebral). The source of hemorrhage was diagnosed with varying degrees of certainty with CT scan in 12 (12%) cases with aneurysms and in 27 (40%) cases with angiomas. Further CT findings were low density lesions in 18 cases indicating vasogenic edma, and calcifications in 10 angiomas. Intravenous infusion of contrast material was necessary to distinguish smaller aneurysms and angiomas. CT scan demonstrated the presence and location of thrombosed portions of giant aneurysms; these findings were less apparent with angiography. In 29 angiomas of medium or large size (macroangiomas) the malformation was demonstrated with CT scan in 25 (86%) cases and with angiography in 26 cases. 3 angiographically occult angiomas were diagnosed with CT as low density lesions and misinterpreted as gliomas. In all 36 microangiomas only the hemorrhage was precisely diagnosed with CT. The microangioma was identified angiographically in 24 cases and histologically in 21. In Sturge-Weber's disease the calcifications may be seen earlier with CT than with skull x-ray.

Circadian fluctuations in the activity of DNA-dependent RNA polymerases I and II in the nuclei isolated from mouse tissues and the significance for pharmacological and toxicological studies on transcription.

For pharmacological and toxicological studies on the effect of drugs on transcriptional processes the basic fluctuation in activity during a 24-h period must be known. We have measured the activity of nuclear and mitochondrial DNA-dependent RNA polymerases in cell fractions from mice kept under defined dark/light and feeding schedules. The following results have been obtained: 1. Circadian variations in the activity of RNA polymerases are especially pronounced in the nuclei of liver tissue. These changes depend predominantly on feeding habits and they are comparatively independent on the dark/light schedule. A maximum in the activity of nuclear DNA dependent RNA polymerases can be observed shortely after the beginning of the feeding period. 2. The nuclei isolated from other tissues, such as brain, kidney or embryos during the late stage of embryogenesis shown considerably smaller, if any, fluctuations in connection with the feeding habits. These tissues seem to be especially suitable for pharmacological or toxicological studies on transcriptional processes. 3. While both nuclear DNA-dependent RNA polymerases shown a strong dependence on the feeding habits no obvious circadian viriations can be observed in the activity of the DNA-dependent RNA polymerase localized in the mitochondrial fractions of the same tissue. The regulation of these polymerases in different cell compartments apparently occurs quite independently. The conclusions for the design of experiments on induction processes occurring in liver tissues, drawn from the results presented, are discussed.

Activity of nuclear DNA-dependent RNA polymerases in mouse limb buds differentiating in vivo or in organ culture.

1) A method was developed to measure the activity of DNA dependent RNA polymerase reactions I (alpha-amanitin-insensitive) and II (alpha-amanitin-sensitive) in homogenates of very small amounts of tissue. This technique was used to study the activity of these polymerase reactions in limb buds from mouse embryos developing in vivo or in an organ culture system. This culture system allows the morphogenetic differentiation of limb buds in early stages of embryonic development (day 10-11 of gestation greater than or equal to 37 - 45 pairs of somites) from a blastema stage to well recognizable cartilaginous bone analgen. 2) An increase in the activities of both types of RNA polymerases was found to occur in vivo in limb buds on day 12 of gestation when compared with the activity measured on day 11 of gestation. A similar increase with a maximum about 24-48h after initiation of the cultures could be observed in the explants differentiating in organ culture. To our knowledge this is the first time that induction processes proceeding in mammalian embryonic tissues could be correlated with an increased activity of RNA polymerases. 3)A rough estimate shows that the rate of transcription due to RNA polymerase I measured in homogenates or in isolated nuclei (measured with substrate concentrations giving about 80% of the maximal rate) would account for the assumed rate of rRNA synthesis in vivo. The measurement of the RNA polymerase activity in isolated nuclei, thus, may give some information about the transcriptional processes occurring under "physiological" conditions. 4) The mammalian organ culture system presented provides a suitable model for studying embryonic differentiation processes.

The influence of externally applied organic substances on phloem translocation in detached maize leaves.

Solutions of organic substances show differing influences on the direction of phloem transport of (14)C-labeled assimilates in predarkened maize leaf strips, when externally applied to one end of the strip. One group of substances "pushes" the assimilates away from the site of application. Examples of this group are 75 mM solutions of sucrose, trehalose, maltose, D-glucose, D-fructose, glucose-6-phosphate, raffinose and galactose. There is strong evidence that "pushing" substances are taken up from the apoplast and loaded into the phloem. Another group of substances attracts the assimilates, it seems to "pull" the assimilates in direction to the site of application. Examples of this second group are 75 mM solutions of arabinose, melibiose, myo-inositol, D-mannitol, polyethylene glycol 2000, and Na2-EDTA (ethylene-diaminetetraacetate). The "pulling" substances obviously are not taken up into living cells. It is assumed that they accumulate in the apoplast and build up a water stress (water potential), which is counteracted by an increase of solute concentration in the parenchyma, thus creating a sink for assimilates. A third group of substances shows inert behaviour, having no perceptible influence on phloem transport, at least not, when applied as 75 mM solutions. At concentrations of more than 300 mM, inert substances tend to attract assimilates like those of the second group. Inert substances are xylose, sorbose, 2-deoxy-D-glucose, mannose and sorbitol.