Optic chiasm glioma associated with inappropriate secretion of antidiuretic hormone,cerebral ischemia,nonobstructive hydrocephalus and chronic ascites following ventriculoperitoneal shunting

An optic chiasm glioma may cause loss of vision, endocrine disturbances, hydrocephalus and cerebral ischemia due to its proximity to the pituitary, hypothalamus, III ventricle and internal carotids. A 3-month-old infant with optic chiasm glioma developed hypopituitarism and inappropriate secretion of antidiuretic hormone with plasma hypo-osmolality. The cerebrospinal fluid (CSF) protein concentration was markedly elevated. The impairment of fluid absorption via arachnoid villi and peritoneum by the high protein content, and reversed osmotic gradient between protein-rich CSF and hypo-osmolar plasma may have contributed to both nonobstructive hydrocephalus and recurrent ascites following ventriculoperitoneal shunting. Cerebral ischemia from carotid compression may have led to cerebral atrophy.     

Effects of unilateral cortex lesions on gene expression of rat cortical cholecystokinin neurons.

In rat neocortex, the gene encoding preprocholecystokinin is expressed in interneurons which also synthetize gamma-aminobutyric acid. An injury to the meninges and the underlying cortex increased the concentration of mRNA coding for preprocholecystokinin in all ipsilateral cortical areas. Simultaneous treatment of the rats with the anti-inflammatory agent diclofenac did not affect the injury-induced change in gene expression indicating that inflammatory processes were not involved. The injury also enhanced the expression of the immediate early gene c-fos in the ipsilateral cortex in a time-dependent manner. There was an increase in c-fos mRNA 1 h after the operation, which was no longer observed 3 h later. Twenty-four hours after the operation, cells containing c-fos mRNA were found in cortical layers II, III, V and VI. The neurons which showed an increased expression of preprocholecystokinin were also in these layers. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 prevented the injury-induced increases in both preprocholecystokinin and c-fos gene expression, indicating that stimulation of this glutamate receptor subtype may initiate the changes in expression of both genes. It is hypothetized that the immediate early gene c-fos is activated first and this then leads to the increase in preprocholecystokinin mRNA.     

Gadolinium-enhanced magnetic resonance imaging in temporal bone lesions

A 2-year experience with an enhancement agent in magnetic resonance imaging (MRI) is examined through case presentations. Characteristics of the agent Gadolinium DTPA/Dimeglumin are reviewed. Radiographic capabilities in enhanced versus unenhanced MRI are compared. Temporal bone lesions, including acoustic neuromas and facial nerve neuromas, are presented. Recent experience with facial nerve enhancement in Bell's palsy is also presented. Greater accuracy in defining small temporal bone lesions and increased delineation of facial nerve involvement appear to be significant benefits with enhanced MRI.     

In vitro and in vivo evaluation of seven 50 mg and 100 mg nitrofurantoin tablets

Four 50 mg and three 100 mg marketed nitrofurantoin tablets were studied in 14 healthy male subjects. Urine was collected 1, 2, 3, 4, 6, 8, 12, and 23 h after each dose, and nitrofurantoin was assayed by HPLC. The in vitro dissolution of the tablets was determined using USP Apparatus 1 and 2, with 0.1 N hydrochloric acid and pH 7.2 buffer as the dissolution fluids. One of the 50 mg tablets was more rapidly and completely absorbed than the other six products. The incidence of side-effects for this product was as low or lower than the other products. It was determined that the use of the USP Apparatus 1, at 100 rev min-1, with sampling of the pH 7.2 fluid at 30 min, provided for the best overall relationship between the urinary excretion and in vitro dissolution.     

Bupropion and nicotine patch as smoking cessation aids in alcoholics.

This is a double-blind placebo-controlled study of sustained-release bupropion as a smoking cessation aid in alcoholics undergoing treatment for their alcoholism. Participants (N=58) were enrolled within 1 week of entry into alcohol treatment from community and Veterans Affairs Substance Use Disorder programs. All participants received nicotine patch and were invited to attend a smoking cessation lecture and group. Cigarette smoking and alcohol outcomes were measured at 6 months. Bupropion when added to nicotine patch did not improve smoking outcomes. One third of participants on bupropion reported discontinuing the drug during weeks 1-4. Participants reported cigarette outcomes with nicotine patch that are similar to those seen in the general population. All study participants significantly reduced cigarette use. Comorbid affective disorder or antipersonality disorder did not affect outcomes. Alcohol outcomes were improved in those who discontinued cigarettes.     

Leukoaraiosis correlates with cerebral hypoperfusion in vascular dementia

Leukoaraiosis quantified by computerized densitometric measurements of reduced Hounsfield numbers was correlated with local cerebral blood flow on the same computed tomographic images of 35 patients with multi-infarct dementia and 16 age-matched elderly normal volunteers. The ratio for area of frontal leukoaraiosis to total area of parenchyma among the patients was significantly greater than that among the normal volunteers (5.8 +/- 2.3% compared with 3.1 +/- 1.3%, p less than 0.001). Severity of leukoaraiosis around the frontal horns of the lateral ventricles correlated significantly with severity of leukoaraiosis of the centrum semiovale adjacent to the bodies of the lateral ventricles. Cerebral blood flow values for all representative cerebral regions except the parietal white matter were reduced among the patients compared with the normal volunteers. Multivariate regression analysis revealed that reduced cerebral perfusion in the putamen and thalamus correlated significantly with the severity of leukoaraiosis. Cerebral hypoperfusion in territories supplied by deep penetrating arteries may contribute to the pathogenesis of leukoaraiosis.     

4,5-Dianilinophthalimide: a protein-tyrosine kinase inhibitor with selectivity for the epidermal growth factor receptor signal transduction pathway and potent in vivo antitumor activity.

Deregulated signal transduction via the epidermal growth factor receptor (EGF-R) family of protein-tyrosine kinase growth factor receptors is associated with proliferative diseases. We describe a class of compounds (4,5-dianilinophthalimides) that inhibit the EGF-R protein-tyrosine kinase in vitro with high selectivity. In cells, 4,5-dianilinophthalmide selectively inhibited both ligand-induced EGF-R and p185c-erbB2 autophosphorylation and c-fos mRNA induction. Antitumor activity could be demonstrated in vivo against xenografts of the A431 and SK-OV-3 tumors, which overexpress the EGF-R and p185c-erbB2, respectively. In contrast, a platelet-derived growth factor-driven tumor was not inhibited by 4,5-dianilinophthalimide, which is compatible with its cellular selectivity and hypothesized mechanism of action. No overt cumulative toxicity was observed during treatment even though high efficacy was observed, indicating a good therapeutic window. 4,5-Dianilinophthalimides may offer therapeutic agents for the treatment of hyperproliferative diseases that overexpress EGF-R family protein-tyrosine kinases or their ligands.     

Hugh Morriston Davies and lobectomy for cancer, 1912

The report of a lobectomy for bronchogenic carcinoma in 1912, by Hugh Morriston Davies of London, and without precedent, describes a surgical technique strikingly similar to that of today. Unfortunately, Davies' patient died because postoperative management of the pleural space was not yet well understood. The tumor had been identified by radiographic examination and the diagnosis confirmed by cytological examination of the sputum. The operative technique included individual ligation of hilar vessels and suture closure of the bronchus, neither of which was to be reported again for more than 20 years. More effective management of the pleural space was described, without special emphasis, by Harold Brunn of San Francisco 17 years later.     

Blood flow distribution and its temporal variability in stimulated dog gastrocnemius muscle

The distribution of blood flow in skeletal muscle stimulated to rhythmic isotonic contractions was studied by injections of radioactive microspheres into the arterial supply in 8 gastrocnemius muscles (mean weight 84 g) of 6 anesthetized dogs (20-25 kg body weight). The distribution of 10 micron microspheres in regions of about 0.5 g was very similar to that of the standard 15 micron microspheres, whereas that of 25 micron microspheres was more uneven. The coefficient of variation (CV = SD/mean) of the ratio of simultaneously injected 10 micron and 15 micron microspheres, 0.12, was taken as the inherent scatter of the method. The average spatial distribution inequality of 10-15 micron microspheres corresponded to a CV of 0.45 and the specific local blood flow inhomogeneity to a CV = 0.43 ( = square root 0.45(2) - 0.12(2], but there were marked differences between muscles. At equal blood flow levels, the inhomogeneity during reactive hyperemia was similar to that observed during stimulation. The temporal variability of blood flow in individual muscle pieces was obtained from the comparison of fractional trapping of 4 to 5 differently labeled microspheres injected at intervals of 2 min into steadily stimulated muscles. The mean CV for the variations in time was 0.23 and that corrected for methodological scatter, 0.19, but the differences in the extent of temporal blood flow changes among muscle pieces within a muscle and between different muscles were large. The presence of considerable spatial and temporal variations of blood flow in exercising muscle during apparent steady state may be important in limiting and/or modulating tissue O2 supply.