A prospective evaluation of changes in neuropsychological and liver function tests following transjugular intrahepatic portosystemic stent-shunt

Background/Aims: This study was designed to assess changes in: (a) neuropsychological tests, measures of memory, quality of life and scores for anxiety and depression; (b) liver function tests; and (c) the relationship between these following transjugular intrahepatic portosystemic stent-shunt.Methods: Twenty-nine patients undergoing transjugular intrahepatic portosystemic stent-shunt for recurrent variceal haemorrhage, 12 matched patients with cirrhosis and variceal haemorrhage manage with variceal band ligation and 16 normal controls were studied. Patients in any of the groups who were clinically encephalopathic were excluded from the study. Serial changes in the conventional liver function tests and Indocyanine green clearance, and psychometric function (Hospital Anxiety Depression Scale, Rivermead Behavioral Memory Test, Quality of Life and the memory and reaction sub-tests of the Cambridge Automated Neuropsychological Test Assessment Battery) were measured prior to and 1, 3, 9 and 15 months following transjugular intrahepatic portosystemic stent-shunt.Results: Over a mean follow up of 9.1 months in the transjugular intrahepatic portosystemic stent-shunt group (range 3–28), one patient (3%) developed clinically detectable encephalopathy. Sixty-seven percent of patients with cirrhosis showed evidence of subclinical encephalopathy as compared with the control population. Significant deterioration occurred in the reaction sub-tests of the Cambridge Automated neuropsychological Test Assessment Battery in patients, both in the transjugular intrahepatic portosystemic stent-shunt group and the controls with cirrhosis, during follow up. Transjugular intrahepatic portosystemic stent-shunt was followed by significant deterioration in levels of anxiety and psychological component of the quality of life. The Rivermead Behavioural Memory Test and the memory sub-test of the Cambridge Automated Neurpsychological Test Assessment Battery did, however, improve significantly at 1 and 15 months after transjugular intrahepatic portosystemic stent-shunt, respectively. Serum alanine aminotransferase, bilirubin and indocyanine green clearance deteriorated significantly following transjugular intrahepatic portosystemic stent-shunt (p<0.001, p<0.001 and p<0.0001, respectively). Significant correlation was observed between changes in the indocyanine green clearance and changes in the complex and simple reaction time subtests of the Cambridge Automated Neuropsychological Test Assessment Battery (r=0.6 and r=0.66, respectively).Conclusions: The results of this study showed that about 67% of patients with cirrhosis were subclinically encephalopathic and that temporary deterioration occurred in the Cambridge Automated Neuropsychological Test Assessment Battery during follow up, both in patients having transjugular intrahepatic portosystemic stent-shunt and in the controls with cirrhosis. These parallel the changes in the liver function tests and indocyanine green clearance. Temporary deterioration was also observed in the Quality of Life and Hospital Anxiety Depression Scale in the transjugular intrahepatic portosystemic stent-shunt group, although the measures of memory improved. Further studies should address the biochemical mechanisms of these changes and the role of prophylactic measures.     

In vitro hydrolysis of steroid acid ester derivatives of prednisolone in plasma of different species

The in vitro hydrolysis of two new classes of steroid acid esters synthesized from prednisolone as local anti-inflammatory steroids was investigated in rat, rabbit, and human plasma. One class was synthesized by incorporating methoxycarbonyl groups at the 16 position of prednisolone to produce 16 alpha-methoxycarbonyl prednisolone (P16CM) and its 17-deoxy analogue (DP16CM). The other class was synthesized by modifying the ketol side chain of prednisolone to produce methyl 20 alpha- and methyl beta-dihydroprednisolonate (P4 alpha and P4 beta). The P16CM and P4 beta were rapidly and completely hydrolyzed within 1 h of incubation in rat and rabbit plasma and within 4 h in human plasma. There was a marked species difference in the hydrolysis of DP16CM which occurred in the following order: rat greater than human greater than rabbit. The in vitro hydrolysis of P4 alpha was much slower than that of P4 beta; the process continued over 24 h in rat plasma. As expected, no change in the initial concentration of prednisolone was found over 120 h of incubation in rat plasma. This marked species difference in the hydrolysis of these steroid acid esters is probably related to the differences in the amounts, types, and activities of the hydrolyzing enzymes (e.g., esterases) in the plasma of the three species. From this study it can be concluded that the existence of an hydroxyl group at C-17 and the orientation of hydroxyl groups at C-20 play an important role in the systemic hydrolysis rate of the carboxy ester group on the steroid nucleus.     

Renal responses to magnesium lithospermate B

Renal responses to magnesium lithospermate B isolated from Salviae miltiorrhizae radix were examined in normal rats. Urinary sodium, potassium, prostaglandin E2 and kallikrein excretion was significantly increased after magnesium lithospermate B administration, whereas excretion of urinary 6-keto-prostaglandin F1 alpha and thromboxane B2 was unchanged. Rats administered with the drug also revealed a slight elevation of plasma renin activity and the levels of angiotensins I and II. Plasma aldosterone was decreased slightly. No significant changes were observed in angiotensin-converting enzyme or blood pressure.     

Protein kinase C isozymes that mediate enhancement of neurite outgrowth by ethanol and phorbol esters in PC12 cells

Using PC12 cells to study ethanol's effects on growth of neural processes, we found that ethanol enhances NGF- and basic FGF-induced neurite outgrowth. Chronic ethanol exposure selectively up-regulates δ and ε protein kinase C (PKC) and increases PKC-mediated phosphorylation in PC12 cells. Since PKC regulates differentiation, we investigated the role of PKC in enhancement of neurite outgrowth by ethanol. Like ethanol, 0.3–10 nM phorbol 12-myristate, 13-acetate (PMA) increased NGF-induced neurite outgrowth. However, higher concentrations did not, and immunoblot analysis demonstrated that 100 nM PMA markedly depleted cells of β, δ and ε PKC. PMA (100 nM) also down-regulated β, δ and ε PKC in ethanol-treated cells and completely prevented enhancement of neurite outgrowth by ethanol. In contrast, the cAMP analogue 8-bromoadenosine cAMP did not completely mimic the effectsof ethanol on neurite outgrowth, and ethanol was able to enhance neurite formation in mutant PC12 cells deficient in protein kinase A (PKA). These findings implicate β, δ or εPKC, but not PKA, in the neurite-promoting effects of ethanol and PMA. Since chronic ethanol exposure up-regulates δ and ε, but not βPKC, these findings suggest that δ or εPKC regulate neurite outgrowth.     

Effect of cyclosporin therapy in controlling the rejection of ileal versus jejunal allografts*

Abstract. Experimental evidence suggests that jejunal allografts are rejected as rapidly as are ileal grafts, despite their lesser content of lymphoid tissue as an immunologic stimulus. However, it may be possible to postpone the rejection of jejunal grafts more readily than that of ileal grafts by means of immunosuppressive therapy with cyclosporin (CyA). To test this, we used the rat model (BN-LEW) of orthotopic small-bowel transplantation. The proximal third of the small-bowel with one-third of the mesenteric lymph nodes (n= 20), or the distal ileal third with all of the mesenteric lymph nodes (n= 22), or the entire small-bowel (n= 23) was interposed after resection of an equivalent type and length of recipient bowel. CyA (15 mg/kg) was given to all of these rats for 5 days. Three additional control groups were not given CyA. The difference in graft/recipient survival among the groups receiving CyA and among those not on CyA therapy was not statistically significant. Antidonor hemagglutinin titers, the mixed lymphocyte culture (MLC) assay, and histologic examination of the allograft failed to show a mitigated rejection reaction for the recipients of jejunal grafts. The data show that short-term treatment with CyA prolongs graft survival. Equal doses of CyA, however, did not lead to prolonged survival of jejunal grafts or alter the course of rejection in comparison with that for ileal or whole-bowel transplants.     

123I-MIBG myocardial scintigraphy as a noninvasive screen for the diagnosis of coronary artery spasm

Background  It has been suggested that the sympathetic nervous system might play an important role in the development of coronary artery spasm. However, no cardiac imaging modality has been able to demonstrate abnormal sympathetic innervation in patients with coronary artery spasm. The purpose of this study was to assess the presence and location of abnormal sympathetic innervation using iodine 123-metaiodobenzylguanidine (¹²³I-MIBG) single photon emission computed tomography (SPECT) and to evaluate the clinical efficacy of ¹²³I-MIBG SPECT as a noninvasive screening test in patients with coronary artery spasm. Methods and Results  Coronary arteriography and a provocative test with intravenous administration of ergonovine maleate were performed in 26 patients (20 men, 6 women, mean age 48.2±12.0 years, range 20 to 67 years) who were suspected of having a coronary artery spasm. The subjects were divided into 2 groups: group 1 (n=18) comprised subjects with negative provocative provocative test result, and group 2 (n=8) comprised subjects with negative provocative test results. Ten healthy subjects served as controls. No abnormal MIBG uptake was observed in the control subjects. Abnormal sympathetic nervous innervation using ¹²³I-MIBG SPECT was observed either as a reduced uptake or a defective pattern in the perfused areas in 13 of the 18 regions supplied by vessels of ergonovine-induced vasospasm. Normal sympathetic innervation, as evidenced by normal ¹²³I-MIBG uptake, was noted in all of the 60 segments of normal vessel territories. Reduced uptake of ¹²³I-MIBG was not detected in the perfused areas of 5 vasospasm-induced vessels (perfusion territory of left anterior descending coronary artery [LAD] and the right coronary artery [RCA] in 2 and 3 patients, respectively). The sensitivity and specificity of ¹²³I-MIBG for detection of coronary artery spasm were 72.2% (95% confidence interval, [CI] 55% to 89%) and 100%, respectively. The positive predictive and negative predictive values were 100% and 92.3% (95% CI 91% to 93%), respectively. Conclusion   ¹²³I-MIBG SPECT is a feasible method to evaluate noninvasively and localize the territories of coronary arteries with spasm. Invasive diagnostic coronary arteriography with ergonovine provocation test may be unnecessary for diagnosis of coronary artery spasm in patients with typical resting pain, negative exercise test or normal thallium perfusion scan results, but showing abnormalities in ¹²³I-MIBG SPECT. Presented in part at the European Association of Nuclear Medicine Congress, September 1996, Copenhagen, Denmark.     

Effects of argon laser iridotomy on the corneal endothelium

We studied 14 eyes of 14 patients undergoing argon laser peripheral iridotomy for occludable (narrow) anterior chamber angles. Preoperative and postoperative pachymetry and corneal endothelial cell counts by specular microscopy were obtained centrally and in both the treated and nontreated superior quadrants. No significant differences were found between preoperative and postoperative measurements of corneal thickness and endothelial cell counts in any area.     

A survey of household food purchases and dietary habits in relation to affluence among Singapore Chinese

A survey of 40 Singapore Chinese households was performed, obtaining information on major perishable foods purchased for home consumption in the previous week, extent of home consumption (eating in), household dietary habits and housing type, the last as a measure of affluence. Eating out was very common: nine (23 per cent) households ate less than 50 per cent of meals at home. Excluding these nine households, consumption and habits were compared between more affluent and less affluent households. The more affluent households purchased more red meat/offal (P = 0.001), poultry (P = 0.002), vegetables other than green leafy (P = 0.04), fruit (P = 0.007) and eggs (P = 0.04); they also differed significantly in various dietary habits. Significant differences were also observed between English-speaking and Chinese-speaking households. The results suggest that increasing affluence may have brought about substantial dietary change in Singapore, thus meriting further study of the role of diet in changing disease patterns in Singapore.