Transjugular intrahepatic portosystemic shunt for refractory ascites: tipping the sodium balance.
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Biomedical subjects
Publications and source records attributed to F Wong.
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A specimen study focused on the measurements of C7 lateral mass and pedicle as well as the projection of pedicle axis on the posterior aspect of the lateral mass was done, based on 56 whole clean, dry, well-preserved spines of skeletally mature adults, 32 males and 24 females. Lateral mass widths averaged 11.7 mm. Lateral mass heights averaged 14.8 mm. The average thickness of the lateral mass was 6.8 mm. The average pedicle widths were 6.2 mm, and the average heights were 7.0 mm. Small, but statistically significant differences were found between the averages of the aforementioned dimensions in the male and female groups. The angulation between pedicle axis and the posterior aspect of the lateral mass averaged 107.0 degrees in the transverse plane and 76.2 degrees in the sagittal plane, respectively. Differences in angulations were not significant when compared according to side or sex of group. Distances from the projection point of pedicle axis to a line passing through the mid-line of the transverse process ranged from 2 mm superior to the line to 4.5 mm inferior, with an average 1.2 mm inferior on right side and 0.3 mm inferior on the left. Distances from the pedicular axial projection point to the outer margin of the lateral mass ranged from 0.0 mm to 5.4 mm, with an average 2.4 mm on the right side and 2.9 mm on the left side. Differences of distance related to left or right side were statistically significant, whereas the distances when related to the sex of the group were not.(ABSTRACT TRUNCATED AT 250 WORDS)
Misoprostol (200 micrograms) has been shown to acutely counteract the indomethacin-induced renal dysfunction in well compensated cirrhotic patients. The aim of this study was to determine if the prophylactic value of misoprostol was dose-dependent. Parameters of renal hemodynamics and tubular sodium and water handling were assessed by clearance techniques in 26 well compensated cirrhotic patients before and after an oral combination of 50 mg of indomethacin and various doses of misoprostol. The 200-micrograms dose was able to totally abolish the deleterious renal effects of indomethacin, whereas the 800-micrograms dose resulted in significant worsening of renal hemodynamics and sodium retention. These changes were maximal in the hour immediately after medications and slowly returned toward base-line levels thereafter. These results suggest that the renal protective effects of misoprostol is dose-dependent. However, until this apparent ability of 200 micrograms of misoprostol to prevent the adverse effects of indomethacin on renal function is confirmed with chronic frequent dosing, it would be prudent to avoid nonsteroidal anti-inflammatory therapy in patients with cirrhosis.
Obliterative lesions in portal veins (PVs) and hepatic veins (HVs) of all sizes are known to occur in cirrhotic livers. PV lesions have generally been attributed to thrombosis, but the pathogenesis of the HV (veno-occlusive) lesions is unknown. We have studied 61 cirrhotic livers removed at transplantation to clarify the prevalence, distribution, and pathogenesis of venous lesions, as well as the association of these lesions with other morphological features and clinical morbidity. Intimal fibrosis that is highly suggestive of healed HV or PV thrombosis was found in at least 70% and 36% of livers, respectively. The distribution of HV lesions was patchy and largely confined to veins between 0.1 and 3 mm in diameter, suggesting multifocal origin in small veins. PV lesions were more uniform throughout the liver, suggesting origin in large veins with propagation to the small veins. HV lesions were associated with regions of confluent fibrosis (focal parenchymal extinction), and PV lesions were associated with regional variation in the size of cirrhotic nodules and a history of bleeding varices. These observations suggest that thrombosis of medium and large PVs and HVs is a frequent occurrence in cirrhosis, and that these events are important in causing progression of cirrhosis.
The aim of this study was to assess baroreceptor function in well-compensated cirrhosis by determining the forearm vascular, renal, and humoral responses to sustained baroreceptor deactivation. The effect of sodium status on baroreceptor function was also assessed. Eight cirrhotic patients and 10 age- and sex-matched controls were studied twice after a 20 mmol and 200 mmol of sodium/d diet for 7 days. Systemic and renal hemodynamics, renal sodium handling, forearm blood flow, and neurohumoral factors were assessed before, during, and after the application of lower body negative pressure (LBNP) for 1 hour. Controls and cirrhotic patients had similar baseline mean arterial pressure, heart rate, forearm and renal hemodynamics. High-sodium intake resulted in suppression of sympathetic nervous activity in the controls (plasma norepinephrine, 1.06 +/- 0.11 nmol/L on low vs. 0.76 +/- 0.08 nmol/L on high sodium; P = 0.01) but not in the cirrhotic patients (1.35 +/- 0.22 nmol/L on low vs. 1.26 +/- 0.11 nmol/L on high sodium; P > 0.05). Both groups responded to LBNP with significant further increases in plasma norepinephrine, resulting in significant decreases in forearm blood flow on both sodium diets. Controls also responded with a significant worsening of renal hemodynamics on low-sodium diet only, but this was not observed in the cirrhotic patients on either diet. Therefore, in well-compensated cirrhotic patients: (1) sympathetic activation occurs despite an adequate, effective arterial filling, and this may contribute to sodium retention; and (2) baroreceptor function is normal. Apparent end organ unresponsiveness within the renal circulation may account for the lack of renal hemodynamic changes to reflex sympathetic stimulation.
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A total of 29 patients with well-compensated alcoholic cirrhosis and 9 healthy control subjects of similar age and sex were studied to assess their response to a challenge of 2 L of normal saline infused over a 1 hr period. Patients with cirrhosis had an adequate effective arterial blood volume in the basal state as assessed by neurohumoral markers of vascular filling. They also had a lower renal vascular resistance (p = 0.048) and a higher glomerular filtration rate (p = 0.014) than the controls, indicating the presence of renal vasodilation. Both groups were in sodium balance, but the patients with cirrhosis had a higher filtered load of sodium, an increased proximal tubular reabsorption of sodium (p = 0.015) and a decreased fractional excretion of sodium (p < 0.001). The administration of a saline load was not accompanied by any significant changes in the renal circulation in the patients with cirrhosis. They were unable to suppress their proximal tubular reabsorption of sodium to the same extent as the controls (p = 0.012), so by the fourth hour a significant difference in the rate of urinary excretion of sodium was evident. In the patients with cirrhosis, glomerular filtration rate before and after the saline load correlated significantly with indocyanine green extraction (r = 0.65; p = 0.002), whereas the tubular handling of sodium was dependent on antipyrine clearance (r = 0.80; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND/AIMS: Prostaglandins are important modulators of renal physiology, particularly when the effective circulatory volume is decreased. The aim of this study was to determine the dose-dependent effects of an oral prostaglandin E1 analogue, misoprostol, on renal function in patients with well-compensated alcoholic cirrhosis. METHODS: Renal hemodynamics and tubular function were assessed by clearance techniques, before and after 100-microgram, 200-microgram, 400-microgram, or 800-microgram oral doses of misoprostol. RESULTS: Overall, the results indicate that low-dose misoprostol is vasodilatory, natriuretic, and diuretic whereas high-dose misoprostol increases renal vascular tone and inhibits sodium and water excretion. The 200-microgram dose produced a transient but significant increase in the glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance. Urinary volume and urinary sodium excretion increased and urinary osmolality decreased. CONCLUSIONS: The results suggest that, in patients with well-compensated cirrhosis, the renal effects of misoprostol are determined by a bell-shaped dose-response curve. The renal vasodilatory, natriuretic, and diuretic potential of 200-micrograms of misoprostol suggests that it may be of therapeutic value in patients with cirrhosis.
Following the administration of 10 mg of nifedipine to 11 patients with well-compensated alcoholic cirrhosis, there was a significant fall in mean arterial blood pressure, accompanied by an increase in heart rate, presumably due to a significant decrease in systemic vascular resistance. Despite the fall in renal perfusion pressure, there was an increase in the effective renal plasma flow and a significant decrease in renal vascular resistance. The glomerular filtration rate was preserved, suggesting that the decrease in renal vascular resistance was due to a preferential decrease in afferent arteriolar tone. There were no significant changes in the filtered sodium load or the tubular reabsorption of sodium and urinary sodium, and urinary volume did not alter significantly. Although the current study indicates that nifedipine can improve the renal circulation in patients with cirrhosis, the significant effects on the systemic circulation suggest that its potential to reverse the intense renal vasoconstriction that can complicate the clinical course of advanced liver disease is unlikely to be of value in the treatment of the hepatorenal syndrome.
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Four babies with congenital listeriosis were diagnosed in the Prince of Wales Hospital in Hong Kong in 1990-1991. Two died in the early neonatal period. The remaining 2 survived and recovered with no sequelae. The clinical and pathological features of these babies, together with those reported in the recent literature are highlighted so as to raise a high index of suspicion toward this disease and hopefully prompt treatment can be offered.
PURPOSE: To determine the pathogenetic mechanism of photoreceptor cell degeneration in the inherited retinal dystrophy in Royal College of Surgeons (RCS) rats. METHODS: The dystrophic retinas of the pink-eyed RCS (RCS-rdy-p) rats were examined for DNA fragmentation by agarose gel electrophoresis of retinal DNA and by TdT-mediated biotin-dUDP nick-end labeling (TUNEL) in paraffin sections. Rats ranging in age from 3 to 60 days were examined. RESULTS: Agarose gel electrophoresis of retinal DNA isolated from animals 25, 30, 35, and 40 days old showed a ladder pattern of degradation with bands corresponding to multiples of 180 to 200 base pair subunits. TUNEL study showed increasing labeling of photoreceptor cells with progression of the retinal dystrophy of the RCS rats. CONCLUSIONS: Apoptosis is the dominant mechanism of photoreceptor degeneration in the RCS rat, which has a genetic defect in the phagocytic activity of retinal pigment epithelium. The onset of the degeneration appeared to vary between rod cells in the different regions of the eye.
In patients with cirrhosis a diminished effective central arterial blood volume associated with systemic arterial vasodilation has been proposed as the mechanism that initiates renal sodium retention. Furthermore, total central blood volume has recently been reported as reduced in cirrhosis, and the controversy over the stimulus for sodium retention in cirrhosis remains. The aim of this study was to assess the central blood volume with radionuclide angiography to determine whether there is effective arterial underfilling in cirrhosis. Twenty-nine patients (13 with and 16 without ascites) and 10 age- and sex-matched control subjects were studied under metabolic conditions. Radionuclide ventricular volume and total central blood volume were determined from gated images, taking into account the 99Tc count activity per milliliter of blood volume and attenuation. The pulmonary volumes were similarly derived.(ABSTRACT TRUNCATED AT 250 WORDS)
Photoreceptors of transgenic mice expressing a mutant rhodopsin gene (Pro347-->Ser) slowly degenerate. The mechanism of degeneration was studied by aggregation of embryos of normal and transgenic mice to form chimeras. In these chimeras, mosaicism was observed in the coat color, retinal pigment epithelium, and retina. In the retina, the genotype of adjacent patches of normal and transgenic photoreceptors was determined by in situ hybridization with a transgene-specific RNA probe. Photoreceptors in the chimeric retina degenerated uniformly, independent of the genotype and similar to the photoreceptors in transgenic mice. However, the chimeric retinas showed varying proportions of normal and transgenic cells. The chimeric retina with a nearly even proportion of normal and transgenic photoreceptors displayed uniform but slower degeneration than that observed in a transgenic mouse of the same age. Our results demonstrate non-autonomy of gene action for the mutated rhodopsin gene and imply that cellular interactions between photoreceptors in the retina probably play a role in degeneration.
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OBJECTIVE: Norrie's disease (ND) is a rare X-linked hereditary disorder characterized by congenital blindness. A putative gene for ND has been isolated and mapped to Xp11.3. Four point mutations in this gene have been identified recently in patients with ND, thus providing strong evidence that this gene is associated with the disease. We report a new mutation. DESIGN: Clinical findings from the proband were correlated with results from DNA analysis. The proband's DNA was compared with that from his mother, an unaffected brother, and four unrelated normal males. PATIENT: The proband was a male infant referred for ocular evaluation at 3 months of age. INTERVENTIONS: The patient was evaluated with a general ocular examination at 4 months of age, a computed tomographic scan at 8 months of age, and then periodic follow-up examinations over the next 7 years. Blood samples were also collected from the proband, his family, and four unrelated normal males. DNA was extracted, amplified using polymerase chain reactions, and then cloned and sequenced. RESULTS/CONCLUSIONS: We identified a new mutation at codon 128 of the ND gene, a dinucleotide GC-to-AA substitution that changed the normal codon for cysteine, TGC, to TAA, which is a stop codon. Thus, this patient lacks the last six amino acids of the carboxyl terminus of the ND protein. The normal ND protein has 11 cysteines in conserved positions that are proposed to be functionally significant. The mutation at codon 128 occurs at the 10th cysteine and might be expected to alter the function of the ND protein. Since the phenotype of this patient is similar to those of other patients with point mutations in the ND gene, this mutation is likely to be the molecular basis of the phenotype.
Evidence is presented which indicates that membrane binding of the murine coronavirus, mouse hepatitis virus (MHV) nucleocapsid (N) protein is mediated by certain lipids. Binding of N protein to membranes of mouse fibroblast L-2 cells is very specific and occurs under conditions in which no other viral or cellular proteins show detectable binding. Binding occurs with both free and nucleocapsid-associated N protein, arguing for membrane-binding sites on the N protein itself, rather than on RNA. Binding of N protein also occurs to membranes in the absence of MHV matrix (M) protein which is known to interact with the N protein. Both non-viral, single-stranded RNA and DNA inhibit membranes. Of various phospholipids tested, cardiolipin was the most effective in inhibiting membrane binding. The N protein was also shown to bind directly to phospholipid liposomes containing cardiolipin as well as to liposomes containing total lipids extracted from mouse L-2 cells. Because of certain structural similarities between phospholipids and nucleic acids, we speculate that membrane lipid association of the N protein may compete for RNA binding sites on the N protein. Such a mechanism may be important for processes such as nucleocapsid uncoating and nucleocapsid assembly. Most interestingly the properties of phospholipid and nucleic acid binding are markedly similar to those recently described for the bacterial DNA-binding proteins DnaA and recA.