Quantitation of apo-, mono-, and diferric transferrin by polyacrylamide gradient gel electrophoresis in patients with disorders of iron metabolism

We have developed a polyacrylamide gradient gel electrophoretic method to quantitate apo-, mono-, and diferric transferrin based upon differences in their molecular size. Purified transferrin saturated to different extents (3% to 98%) with iron showed proportions of the three forms as predicted from an approximately random distribution of iron between the two metal-binding sites. The iron distributions in sera of 14 normal individuals similarly correlated with the predicted values. In contrast, 22 of 43 patients with diseases associated with abnormalities in iron or transferrin metabolism had a disproportionate increase in monoferric transferrin. This abnormality occurred in seven of nine patients who had received bone marrow transplants, seven of 14 with chronic liver disease, and eight of nine menstruating women with probable iron deficiency anemia. Interestingly, 11 patients with malabsorption or chronic renal disease had normal iron distributions. The finding of abnormal distributions of iron on transferrin suggests that gradient gel analysis may be a useful tool for studying the physiologic mechanisms controlling iron utilization.     

Partial versus total portacaval shunt in alcoholic cirrhosis. Results of a prospective,randomized clinical trial.

OBJECTIVE: Results of the first prospective randomized clinical trial comparing partial and total portacaval shunt for variceal hemorrhage are reported. SUMMARY BACKGROUND DATA: Total portacaval shunts produce subnormal portal pressures, completely diverting hepatic portal flow. Partial shunts maintain higher pressures and preserve hepatopedal flow. No randomized trials of these two approaches have been performed. METHODS: Alcoholic patients with cirrhosis (n = 30) and variceal hemorrhage treated at one institution were randomized to receive partial (8-mm diameter portacaval H grafts with collateral ablation, n = 14) or total shunts (16-mm diameter grafts, n = 16). Portography was performed after operation and then yearly. Investigators blinded to shunt type assessed encephalopathy; hospitalizations were reviewed. RESULTS: Child''s class, age, and operative urgency were similar for the two groups. Two patients (with total shunts) died within 30 days. Hepatopedal flow was maintained in 13 partial and 0 total shunt patients (p < 0.0001). Shunt gradients were 16 +/- 5 compared with 6 +/- 3 cm saline after partial and total shunts (p < 0.0001). There were no shunt thromboses or variceal hemorrhages. Encephalopathy-free survival was significantly greater after partial shunts (p = 0.013; life table analysis). Five total compared with zero partial shunt patients required hospitalization for coma (p = 0.02). Long-term survival was not different for the two groups of patients. CONCLUSIONS: Partial shunts control variceal hemorrhage while maintaining hepatopedal flow and elevated portal pressures. By minimizing encephalopathy rates, partial shunts provide improved quality of survival compared with total shunts.     

Portal vein thrombosis associated with cirrhosis: clinical importance.

A group of 86 cirrhotics undergoing therapeutic variceal decompressive procedures were studied. Patients with portal vein thrombosis (PVT) comprised 21% of the group and more frequently had uncontrollable hemorrhage at an earlier stage of liver disease. Mortality in the 18 cirrhotics with PVT was higher (56%), mostly as a result of rebleeding. Despite adjustments for stage of liver disease and type of operation, in no cirrhotic with PVT did postshunt encephalopathy develop, compared with 32% incidence in patients without PVT (P less than .05). It is concluded that patients with cirrhosis and PVT represent a different subpopulation of cirrhotics. Once adequate variceal decompression has been achieved, their prognosis should be superior to cirrhotics without PVT because their hepatic hemodynamics are unaffected by total shunting, hence precluding further impairment of liver function as a result of acute reduction of hepatic blood flow.     

Does portal pressure influence direction of portal flow and encephalopathy rates after 10-mm portacaval shunts in man?

Direction of portal flow after small diameter portacaval H graft has been found to significantly correlate with postshunt portasystemic encephalopathy rates. While some patients maintaining prograde portal flow were found to have a lower incidence of portasystemic encephalopathy, it has been suggested that high portal pressures are responsible for minimizing this complication. If both statements are true, then postshunt pressures should be higher in patients with prograde flow and in encephalopathy. Portal pressure and portal flow patterns were determined by shunt cannulation and fluoroscopy in 16 patients fully recovered from operation. Patients were screened for portasystemic encephalopathy over a 6- to 24-month period (average 12 months) at which time shunt patency was documented. Portal pressures were similar in patients with and without portasystemic encephalopathy and in patients with and without prograde flow. These results do not support the concept that portal pressure is an important determinant of portasystemic encephalopathy rates or flow patterns after 10-mm portacaval H graft.     

Absolute ethanol injection of the adrenal artery: hypertensive reaction

Transcatheter injection of 0.4 ml of absolute ethanol into the adrenal artery was performed in three Rhesus monkeys. The injection produced a mean increase of 60 mmHg in systolic blood pressure and 50 mmHg in diastolic blood pressure within two minutes. Hypertension was accompanied by cardiac arrhythmias (two monkeys) and sinus tachycardia (one monkey). These changes were probably related to an acute catecholamine release. Embolization of the inferior phrenic artery with Gelfoam powder produced only a mild blood pressure elevation in three monkeys (6 mmHg systolic pressure and 10 mmHg diastolic pressure).     

Clinical significance of erosive gastritis in patients with alcoholic liver disease and upper gastrointestinal hemorrhage

Since, in many patients with alcoholic liver disease and upper gastrointestinal hemorrhage, varices and erosive gastritis frequently coexist, the purpose of this study was to assess the severity of hemorrhage, rebleeding and mortality rates when these lesions are present singly or concomitantly. In 104 patients not operated upon, 31 had both lesions present on endoscopic examination, and their clinical courses paralleled the severity of 29 patients who had bleeding varices as the sole finding. In 13 patients with alcoholic liver disease and upper gastrointestinal hemorrhage who were found to have erosive gastritis as the sole lesion, the clinical course was as benign as in 31 patients with ethanol-induced gastritis without liver disease, and their blood loss, rebleeding and mortality rates were significantly less than in patients with both varices and gastritis. It is concluded that the course and prognosis of upper gastrointestinal hemorrhage in patients with alcoholic liver disease and erosive gastritis is dependent upon the presence or absence of gastroesophageal varices.     

Quantitation and fractionation of nutrient hepatic blood flow in normal persons, in persons with portal hypertensive cirrhosis, and after small-diameter portacaval H grafts

Patients maintaining portal perfusion following small-diameter portacaval H grafts have better survival and lower portasystemic encephalopathy rates than those with reversed flow. To determine why this is so, we measured nutrient hepatic blood flow with the use of 99m-Tc-diisopropyl-IDA (DISIDA) clearance pharmacokinetics fractionated into its hepatic arterial and portal venous components. Patients with cirrhosis and portal hypertension had significantly lower nutrient hepatic blood flow than normal persons; this was due almost entirely to reduced portal flow. In patients with prograde portal flow after small-diameter H grafts nutrient hepatic blood flows were nominally reduced from levels seen in patients with portal hypertensive cirrhosis. Postoperative patients with reversed portal flow had significantly less nutrient hepatic blood than those with prograde flow. There was no evidence of significant hepatic arterial compensation for lost portal flow. Of four hemodynamic variables--portal flow direction, portal flow, arterial flow, and nutrient hepatic blood flow--only nutrient hepatic blood flow showed an independent correlation with clinical outcome. Portal perfusion is a critical factor in maintenance of adequate nutrient hepatic blood flow, primarily because hepatic arterial flow does not compensate chronically for lost portal perfusion.     

Pharmacodynamics and pharmacokinetics after repeated subcutaneous administration of three gonadotrophin preparations

Recently, several new urinary gonadotrophin preparations have been developed, containing less luteinizing hormone (LH) activity than human menopausal gonadotrophin. Normegon is a gonadotrophin preparation with a follicle stimulating hormone (FSH)/LH ratio of 3:1; Follegon and Metrodin-HP are purified FSH preparations. The aim of the present randomized study was to compare pharmaco-dynamics, -kinetics and local tolerance of these preparations after repeated s.c. administration. Thirty-six healthy female subjects were treated with Lyndiol contraceptive pills for 5 weeks to suppress endogenous gonadotrophin concentrations. After 3 weeks of Lyndiol treatment, 150 IU of Normegon, Follegon or Metrodin HP were administered once daily, s.c. for 7 days. Blood samples were collected once daily during the fourth and fifth weeks of the study and assayed for FSH and oestradiol. After the last gonadotrophin injection, blood samples were collected more frequently to determine pharmacokinetic parameters of FSH. During the fourth and fifth study weeks, daily ultrasound measurements of follicular growth were performed. Endogenous FSH and LH values were extremely suppressed during Lyndiol treatment. Serum FSH values showed similar patterns in the three groups. The maximum FSH concentration was reached 9-11 h post- injection, the terminal half-life was 43-47 h. The preparations were bioequivalent with respect to FSH immunoreactivity. The number of follicles tended to be larger after Normegon than after Follegon and Metrodin HP treatment, though this was not statistically significant. Serum oestradiol concentrations were significantly higher after Normegon treatment. In general, s.c injections were well tolerated. In conclusion, the three preparations were bioequivalent with respect to FSH immunoreactivity. Nevertheless, the biological activity of Normegon tended to be higher than that of Follegon and Metrodin HP in Lyndiol- suppressed women.