The effect of angiotensin II on haemodynamic and plasma noradrenaline responses to tyramine infusion in man

Summary Six normal volunteers were studied on four separate occasions. On each occasion they received two concomitant infusions which were either placebo/placebo, placebo/tyramine, angiotensin II/placebo or angiotensin II/tyramine. Angiotensin II infusion was given at a constant rate of 2ng/kg/min whereas the tyramine infusion consisted of 10 min increments at 1.25, 2.5, 3.75, 5, 7.5 and 10 g·kg^–1·min^–1.Tyramine infusion caused a dose dependent increase in systolic blood pressure with increases in diastolic blood pressure and plasma noradrenaline only at the highest doses. These changes were not affected by concomitant angiotensin infusion.We have therefore found no evidence to support the enhancement of haemodynamic or plasma noradrenaline responses to tyramine infusion by low dose infusion of angiotensin II in man.     

Effect of tetrakis-μ-3,5-diisopropylsalicylatodiaquodicopper(II) on the status of reduced glutathione in freshly isolated hepatocytes

Effects of different concentrations of tetrakis--3,5-diisopropylsalicylatodiaquodicopper(II) (Cu(II)₂(3,5-DIPS)₄(H₂O)₂) on the reduced status of glutathione (GSH), the major nonprotein thiol in tissues, were investigated using freshly isolated hepatocytes. Cu(II)₂(3,5-DIPS)₄ below 100 M did not have any significant effects on either the GSH content or viability of the hepatocytes, but at 150–250 M it decreased both parameters after 1 h of incubation. The decrease in cellular GSH was not followed by an increase in the oxidized form of GSH (GSSG) in the cell suspension. The addition of deferoxamine with Cu(II)₂(3,5-DIPS)₄ to the hepatocyte suspension prevented depletion in GSH content and loss of cell viability by Cu(II)₂(3,5-DIPS)₄. Both GSH depletion and loss of cell viability were found to be Cu(II)₂(3,5-DIPS)₄ dose dependent. From these results, it appears that Cu(II)₂(3,5-DIPS)₄ penetrated the cell membrane and acted by decreasing the GSH level by forming a copper-glutathione complex.     

Congenital leiomyoma of the distal ileum associated with ileal atresia and malrotation

A leiomyoma of the small bowel in a neonate was found causing luminal occlusion and was associated with malrotation. This association and the lack of intestinal mucosa at the level of the tumor suggest that the growth originated at or near the solid core stage of intestinal development.     

Brain Angiotensin II Receptor Subtypes and the Control of Luteinizing Hormone and Prolactin Secretion in Female Rats

The present experiments examined the role of the two recently identified angiotensin II (Ang II) receptor subtypes, AT, and AT(2) , in the central nervous system regulation of luteinizing hormone (LH) and prolactin secretion in estrogen- and progesterone-treated ovariectomized rats. In this animal model, intracerebroventricular (icv) injection of Ang II stimulates LH and inhibits prolactin release. The specific Ang II receptor subtype antagonists losartan (AT(1) ) or PD123177 (AT(2) ) were administered (icv) in various doses (10 ng to 1,000 ng) 10 min prior to icv injection of Ang II (100 ng). Control animals were pretreated with artificial cerebrospinal fluid prior to Ang II administration. Blood samples for LH and prolactin determinations were taken from conscious, freely-moving rats prior to and following injection of the antagonists and Ang II. Water intake was measured. Ang ll-induced water intake was attenuated 62% by 1,000 ng losartan; water intake was not affected by lower doses of losartan or by any dose of PD123177. Ang ll-induced stimulation of LH release was abolished by the 1,000 ng doses of losartan and PD123177 and attenuated by the 500 ng doses of both drugs. Lower doses did not affect Ang ll-induced LH secretion. Ang ll-induced inhibition of prolactin release was significantly reduced by the 1,000 ng doses of both losartan and PD123177. Lower doses of either drug did not affect the Ang II inhibition of prolactin release. Previous studies had shown that Ang II administration into the anterior hypothalamus-medial preoptic (AHPO) area stimulated LH release. This brain area contains AT(1) receptors. To investigate the potential brain site where the AT(2) receptor may influence LH release, Ang II was injected into the locus ceruleus, a brain nucleus which contains predominately the AT(2) receptor subtype. Ang II administration into the locus ceruleus was paired with an injection of artificial cerebrospinal fluid or Ang II into the AHPO area. Injection of Ang II into the AHPO area stimulated LH release. Injection into the locus ceruleus did not affect LH secretion, nor did it modify the rise in LH elicited by administration of Ang II into the AHPO area. Plasma levels of prolactin were not altered by any of these injections. Taken together, these data demonstrate that, in estrogen- and progesterone-treated female rats, icv Ang ll-induced water intake is mediated by the AT, receptor subtype, while Ang ll-induced changes in LH and prolactin secretion appear to be mediated by both the AT(2) and AT(2) receptor subtypes. The latter observations are one of the first suggesting a potential function for the AT(2) subtype in vivo, although the physiological relevance of this observation, as well as the site of action for the effects on LH and prolactin, remain to be established.     

Paediatric medulloblastoma: Atypical CT features at presentation in the SIOP II trial

Summary A review of cranial CT studies of 233 patients for the Second Medulloblastoma Trial of the International Society of Paediatric Oncology showed typical CT appearances in only 30% of patients. The varied appearances encountered are described with particular emphasis on atypical CT features.A shorter version of this paper was published in the Proceedings of the XIV Symposium Neuroradiologicum (Neuroradiology (1991) 33 [Suppl]: 516–517)     

The compensatory ‘rebound’ of reactive astrogliosis: glial fibrillary acidic protein immunohistochemical analysis of reactive astrogliosis after a puncture wound to the brain of rats with portocaval anastomosis

Summary This study was designed to compare the degree of reactive astrogliosis occurring around a puncture wound in the brain of normal rats and at different intervals after a similar puncture wound in rats with a portocaval anastomosis. The gliosis was evaluated by the number of astrocytes, the thickness of their processes and the intensity of the glial fibrillary acidic protein immunoreactivity. After the puncture wound in the brain of rats with a portocaval anastomosis, the gliosis varied at different intervals being: (1) decreased at 10 days, (2) markedly increased at 5 weeks and (3) significantly decreased at 8, 12, and 16 weeks. These findings suggest that 5 weeks after portocaval anastomosis, an active proliferation of the metabolically altered astrocytes occurs with heightened synthesis of glial fibrillary acidic protein in the period of adaptive compensation, the so-called compensatory rebound. At 8 weeks or more after portocaval anastomosis, these altered astrocytes were considered to be in the phase of decompensation and incapable of maintaining the reactive response which occurred in normal rats. The compensatory rebound and decompensatory decline illustrate the dynamic plasticity of the reactive astrogliosis.Supported by grant from the National Foundation of Natural Sciences No. 386-0956. This paper was read at the XIth International Congress of Neuropathology, September 7, 1990 in Kyoto, Japan     

Auditory toxicity effects of long-term cis-dichlorodiammineplatinum II therapy in genitourinary cancer patients

To determine the auditory toxicity effects of long-term cis-dichlorodiammineplatinum II therapy, pure tone hearing thresholds were measured prior to therapy and repeated before each subsequent treatment. CDDP was given by a slow intravenous drip method at a low dose of 1 mg/kg body weight, with 37.5 gm mannitol, once a week for six treatments and every 3 weeks thereafter. From a group of 173 genitourinary cancer patients treated, 50 male patients were selected who received at least 12 months of CDDP with no active conductive ear pathology, and whose audiograms obtained at baseline, 6th weeks, 26th weeks, and 52nd weeks of treatment were all available for comparison. Pure tone threshold levels deteriorated across time particularly by the 52nd week and at the higher frequencies. Threshold differences across time were statistically significant and within a linear trend. Of the 50 cases, 30% showed suspect or no ototoxicity, 26% mild, 32% moderate, 2% marked, and 4% showed severe ototoxic changes. Of the two cases who developed severe ototoxicity, one showed complete recovery. There was partial recovery in 26% and no recovery in 54%. Individual variability in susceptibility to and recovery from ototoxicity necessitates systematic audiometric monitoring throughout the therapy.     

Regulation of the biosynthesis and processing of chromogranins in organotypic slices: influence of depolarization, forskolin and differentiating factors

Slices from rat hippocampus in organotypic culture were used to study the biosynthesis regulation of chromogranins A and B and secretogranin II. Additionally, we investigated the proteolytic conversion of secretogranin II and the levels of prohormone convertases putatively involved. Forskolin treatment and depolarization with potassium plus BayK 8644 led to significant increases in secretogranin II mRNA in the principal cells of the hippocampus. Enhanced expression of secretogranin II was also reflected by a rise in peptide levels. Despite this induction of biosynthesis the extensive processing to secretoneurin normally observed in brain was maintained. Both forskolin and depolarization upregulated the prohormone convertase (PC)1, but not PC2, indicating that PC1 levels are critical for secretoneurin production under stimulating conditions. Results obtained for chromogranins A and B were less consistent. For chromogranin A mRNA, changes were restricted to granule cells; for chromogranin B, a response in granule cells was observed to depolarization but not to forskolin, and effects in pyramidal neurons were weak. Accordingly, we were unable to detect alterations in chromogranin A and B protein levels. Furthermore, we tested several neurotrophic growth factors and found that only basic fibroblast growth factor raised secretogranin II expression without affecting chromogranins A and B. The hippocampal slice preparation allowed well controlled treatment with identification of neuronal subpopulations and yielded data largely matching experiments in vivo and in cell culture. The pronounced regulation of secretogranin II and its effective processing underlines the importance of the resulting peptide secretoneurin as an active neuropeptide in the nervous system.     

Hypomanic switching caused by the psychological effects brought on by a change in environment due to hospital admission: two cases of bipolar II patients who showed a hypomanic switch

Hypomanic episodes in two cases involving depressed patients (bipolar II) were observed after admission to an open psychiatric ward. The patients had not exhibited any prior (hypo)manic episodes during outpatient treatment. Thus, manic switching was thought to have been caused by the psychological effects brought on by the change in environment due to hospital admission. Hospital admission was believed to have been an unloading from their stressful lives, given that the affective state of both patients prior to admission was characterized by depression resulting from work-related stress. The close relationship between the patients and the predominantly female nursing staff may have triggered a psychological regression in both patients. These factors appear to have led to the hypomanic switching.     

Imaging of the symptomatic type II accessory navicular bone

Accessory ossicles of the foot are commonly mistaken for fractures. The accessory navicular is one of the most common accessory ossicles of the foot. There is a higher incidence in women and the finding might be bilateral in 50?90%. This entity is usually asymptomatic, although populations with medial foot pain have a higher prevalence. Three types of accessory navicular bone have been described. The type II accessory navicular is the most commonly symptomatic variant with localized chronic or acute on chronic medial foot pain and tenderness with associated inflammation of overlying soft tissues. Plain radiographic identification of the accessory navicular is insufficient to attribute symptomatology. Ultrasound allows for comparison with the asymptomatic side and localization of pain. Bone scintigraphy has a high sensitivity but positive findings lack specificity. Magnetic resonance imaging is of high diagnostic value for demonstrating both bone marrow and soft tissue oedema.