Value of transcranial Doppler indices in predicting raised ICP in infantile hydrocephalus. A study with review of the literature

Cerebral hemodynamic changes in infants with progressive hydrocephalus have been studied with the transcranial Doppler (TCD) technique. Several authors have referred to the correlation between the hemodynamic changes and increased intracranial pressure (ICP). Despite conflicting conclusions on the value of pulsatility index (PI) and resistance index (RI) measurements for monitoring infantile hydrocephalus, these pulsatility indices are the most commonly used for this purpose. Although clinical signs of raised ICP are highly variable and unreliable in infants, assumptions have been made in most of the studies about the presence of elevated ICP on the basis of the patient's clinical state. Few studies have reported on actual ICP values, however, and a direct relationship between ICP and TCD changes has never been adequately demonstrated. In the present study, this relationship was investigated in long-term simultaneous TCD/ICP measurements, in an attempt to develop a noninvasive method of monitoring the effect of ICP on intracranial hemodynamics. Two groups of data sets were established. Group I consisted of pre- and postoperative (shunt implantation) TCD/ICP measurements. Group II were long-term simultaneous TCD/ICP recordings showing significant ICP variations. In most of the postoperative measurements there was a decrease in the average PI and RI values. The correlation between PI or RI and ICP in the long-term simultaneous recordings, however, was generally poor. The risk of obtaining false positive or false negative PI or RI values in short-term measurements was also demonstrated. It can be concluded from our results, besides the wide range of reference values for the Doppler indices and extracranial influences upon them, that the present Doppler indices are inadequate for monitoring the complex intracranial dynamic responses in patients with raised ICP.     

Diazepam alters caffeine-induced effects on beta-endorphin levels in specific rat brain regions

The present study was conducted to evaluate the effects of caffeine and the benzodiazepine agonist diazepam, and a combination of both on beta-endorphin (beta-EN) levels in specific rat brain regions. Male Sprague-Dawley rats (150-200 g) adapted to a 12-hour light: 12-hour dark illumination cycle were used in this study. Caffeine (10 mg/kg), diazepam (2 mg/kg) or a combination of caffeine (10 mg/kg) and diazepam (2 mg/kg) were administered intraperitoneally to rats at 11:00 hr. Control animals were injected with saline. Animals were sacrificed by decapitation 1 h after injection, the brains were immediately removed; the cortex, hippocampus, hypothalamus and midbrain were dissected and their B-EN levels measured by radioimmunoassay. Caffeine administration significantly increased B-EN levels in the cortex. Similarly, administration of diazepam alone resulted in a significant increase of B-EN levels in cortex. However, concurrent administration of diazepam and caffeine resulted in higher increase of B-EN levels in cortex. No significant changes in B-EN levels were detected in hippocampus and midbrain after administration of either caffeine or diazepam alone. On the other hand, when diazepam and caffeine were concurrently administered a significant increase of B-EN levels were observed in the midbrain. Moreover, administration of diazepam alone resulted in a significant increase of B-EN levels in hypothalamus. This increase was still observed following concurrent administration of diazepam and caffeine. These results clearly indicate that diazepam alters caffeine-induced effects on B-EN in specific rat brain regions.     

Quenched BODIPY dye-labeled casein substrates for the assay of protease activity by direct fluorescence measurement

We have prepared casein conjugates of two BODIPY dyes for use as fluorogenic protease substrates in homogeneous assays. Both conjugates are labeled to such an extent that the dyes are efficiently quenched in the protein, yielding virtually nonfluorescent substrate molecules. These fluorogenic substrates release highly fluorescent BODIPY dye-labeled peptides upon protease digestion, with fluorescence increases proportional to enzyme activity. These quenched substrates are suitable for the continuous assay of enzymatic activity using standard fluorometers, filter fluorometers, or fluorescence microplate readers using either fluorescein excitation and emission wavelengths to measure BODIPY FL casein hydrolysis or Texas Red wavelengths to detect proteolysis of BODIPY TR-X casein. Most current techniques for detecting protease activity, such as the fluorescein thiocarbamoyl casein (FTC-casein) protease assay, require extensive manipulation, including separation steps, and are therefore labor intensive and error-prone. In comparison, we found the BODIPY dye-labeled casein protease assays to be simple and precise and to have greater sensitivity and a broader dynamic range of detection than the FTC-casein assay. We were able to sensitively detect the activities of a wide variety of enzymes with these new substrates, including serine, acid, sulfhydryl, and metalloproteases. We also found the assay suitable for quantitating protease inhibitor concentrations and for real-time analysis of proteolysis.     

Na+ channel modulation and force-frequency relationship in human myocardium

Insect cell lines in culture are used for a variety of studies. In this laboratory imaginal disc cell lines have been established from primary cultures from third instar larvae, and used for a number of experiments. The effect of ageing on the morphology and physiology of Drosophila cell lines has received very little attention, although problems of genotypic or phenotypic changes in cell lines with age are recognized in other areas of animal cell culture. We tested our cell line Cl8+ for any difference in growth, morphology and response to 20-hydroxyecdysone (20HE) at different ages (passage numbers). The cells were found to multiply faster, adhere less firmly to the substrate and to lose the tendency to aggregate at higher passages. The response to 20HE in terms of cell numbers and induction of beta-galactosidase was similar at all passage numbers but morphological changes in hormone-treated cells were less obvious in the higher passages. Cell lines are likely to vary in the extent of ageing effects but workers are advised to be aware of the possibilities. We suggest the effects of age on cell lines should be established, and passage numbers noted in experimental reports.     

Anatomical suitability of abdominal aortic aneurysms for endovascular repair

BACKGROUND: Aortic aneurysm anatomy is crucial when considering patients for endovascular repair. The aim of this study was to determine the proportion of patients with aortic aneurysm suitable for endovascular repair with three different graft-stent systems. METHODS: Spiral computed tomographic angiography was used to assess the anatomy of 154 abdominal aortic aneurysms. Measurements were made of aneurysm neck length and diameter, renal artery to aortic bifurcation length, common iliac artery diameter and length, and external iliac artery diameter. Aneurysms were assessed for anatomical suitability for currently available aortoaortic, aortobi-iliac and aortouni-iliac devices. RESULTS: Six patients (4 per cent) had a distal aortic neck suitable for implantation of a straight aortic graft. Fifteen patients (10 per cent) had arterial anatomy suitable for implantation of a bifurcated graft and 85 (55 per cent) patients were suitable for endovascular repair with an aortouni-iliac graft. The primary reasons for unsuitability were: proximal neck length less than 1.5 cm (44 patients), proximal neck diameter greater than 3.0 cm (12), and angulation of the proximal neck (three). A further ten patients were considered unsuitable for an aortouni-iliac graft because of bilateral common iliac artery aneurysms (four), tortuous iliac arteries (four) and narrow external iliac arteries (two). CONCLUSION: The aortouni-iliac device has the widest applicability of the currently available endovascular systems but open repair remains the only option for a large proportion of patients.     

Human thalamic nucleus mediating taste and multiple other sensations related to ingestive behavior

Until now, taste was the only primary sensory modality for which the human central nervous system pathways were unknown. We report sensations evoked by stimulation at microampere current levels in the region of the human thalamic nucleus (ventralis caudalis parvocellularis internis) corresponding to the monkey taste relay nucleus. Stimulation in this region during awake neurosurgical procedures evoked special visceral/somatic (taste/pungent smell), general visceral (fullness of a hollow viscus), as well as painful and nonpainful general somatic sensations. General somatic or visceral sensation was evoked by stimulation at 80% of sites where special visceral/somatic sensation was evoked. These results suggest that primate taste relay mediates multiple sensations in addition to taste.     

Actions of cisplatin on the electrophysiological properties of cultured dorsal root ganglion neurones from neonatal rats

In this study we have employed the whole cell patch clamp technique to investigate the effects of an anti-cancer drug cisplatin on basic electrophysiological properties of cultured dorsal root ganglion neurones from neonatal rats. The results show that within the clinical concentration range, cisplatin (0.1 to 10 microM) caused a decrease in input conductance, and complex changes in resting membrane potential in these cultured sensory neurones. The dominant effects of cisplatin on input conductance may be due to inhibition of leak conductances. Transplatin (5 microM) was significantly less effective than cisplatin at reducing input conductance which suggests a degree of stereoselectivity. Cisplatin (1 to 5 microM) transiently increased excitability of the cultured neurones as reflected by a reduction in the threshold for activation of action potentials by 8 mV. The rise time, peak amplitude and duration of action potentials were not changed by acute application of 5 microM cisplatin. Long term treatment of neurones with cisplatin (5 microM), for up to 1 week reduced the viability of the cultures, and attenuated neurone excitability, although input conductance of the cells was significantly increased to 322 +/- 49 M omega (n = 9) compared with controls of 210 +/- 20 M omega (n = 30; P < 0.05). Acute and chronic treatment of cultured neurones with cisplatin therefore produced contrasting actions.     

Hearing and Sj?gren's syndrome

Immune sensorineural hearing loss is manifested in several systemic immune diseases. Although hearing loss has been previously documented in patients with Sj?gren's syndrome (SS), the effect of SS on hearing is unclear. This prospective study was designed to assess the presence of hearing loss in 14 patients with SS and, if sensorineural hearing loss was present, to determine if the hearing loss was immune-mediated. Patients were evaluated with basic audiologic tests as well as for cellular immune inner ear reactivity as measured by the lymphocyte transformation test (LTT). Three patients had evidence of sensorineural hearing loss. Two patients had a positive LTT without evidence of sensorineural hearing loss. This preliminary study suggests that SS may not directly cause sensorineural hearing loss, immuno-mediated or otherwise.