The clearance of a single i.v. bolus of recombinant human erythropoietin from the serum of patients with myelodysplastic syndromes and its effects on erythropoiesis.

The serum erythropoietin (EPO) concentration in patients with myelodysplasia (MDS) varies widely at similar hemoglobin concentrations, although the reasons for this variation are unclear. We have studied the pharmacokinetics of an i.v. bolus of recombinant human EPO in ten subjects with myelodysplasia. Basal serum EPO concentration varied from 210 to 5984 mU/ml. Plasma half-time clearance (t1/2) varied from 3.9 to 20.0 h. A significant positive correlation was found between t1/2 and basal EPO concentration. An increase in immature peripheral blood reticulocytes was found on days 1 and 2 after EPO treatment; this may represent either an effect on hemopoiesis or on reticulocyte release from the bone marrow.     

Orthotopic liver transplantation at Groote Schuur Hospital.

We present data on 10 patients (5 men and 5 women, aged 21-56 yrs) with end-stage liver disease or tumour who underwent orthotopic liver transplantation at Groote Schuur Hospital between October 1988 and June 1991. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the implantation of the liver. The venovenous bypass method was used in all but 2 patients. Postoperative immunosuppression was usually achieved with cyclosporin, azathioprine and low-dose steroids. Six patients were treated with prophylactic OKT3. Rejection episodes were treated with bolus doses of intravenous steroids. The indications for liver transplantation included chronic active hepatitis progressing to cirrhosis (5), biliary cirrhosis in association with inflammatory bowel disease (1), sclerosing cholangitis (2), alpha 1-antitrypsin deficiency (1), and tumour (1). All patients with chronic liver disease had experienced at least one complication, examples of which included encephalopathy, bacterial peritonitis, ascites, variceal bleeding and septicaemia. Serious postoperative complications included acute rejection of the transplanted liver, renal and liver failure that responded to intensive care support and medical management. One patient died on the 11th postoperative day with complications of bleeding oesophageal ulcer, shock and fungaemia. The remaining patients are alive and well 1-31 months after transplantation.     

Acute peripheral arterial and graft occlusion: treatment with selective infusion of urokinase and lysyl plasminogen

Thirty-five patients hospitalized for recent angiographically documented arterial occlusion in the legs (27 femoropopliteal arteries and eight grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a 4- or 5-F catheter. This therapy combined a continuous urokinase (UK) infusion of 1,000 U/kg/hour and a lysyl plasminogen (LYS-PLG) infusion of 15 microkatals every 30 minutes. Angiographically confirmed lysis was obtained in 85% of the cases. Only 3% of the patients had major and 6% had minor groin hematomas. Only two patients had concentrations of fibrinogen as low as 100 mg/dl. Intravascular infusion of UK-LYS-PLG is as effective as streptokinase. Its excellent tolerance makes it a good alternative in the treatment of acute ischemia in the lower limbs.     

Insulinlike growth factor 1 production is inhibited in human sepsis

We studied the response of 14 normal volunteers and five septic patients to a 48-hour course of exogenous biosynthetic human growth hormone (hGH) or placebo. Six normal controls (group 1) received saline, eight normal controls received hGH (group 2), and five septic patients also received biosynthetic hGH (group 3). Urinary urea excretion declined, and splanchnic amino acid uptake was maintained only in group 2 subjects. Septic patients exhibited changes in amino acid and urea dynamics comparable to those of subjects receiving placebo. Insulinlike growth factor 1 (IGF-1) production and plasma concentrations increased in group 2 in a fashion corresponding to the changes in nitrogen exchange, whereas septic patients exhibited no change in IGF-1 level. Therefore, in this septic patient group, exogenous hGH was ineffective in attenuating nitrogen losses and stimulating IGF-1 production. This supports the hypothesis that IGF-1 is a mediator of the anabolic effect of hGH.     

Cardia: study design, recruitment, and some characteristics of the examined subjects

In 1984, a prospective cohort study, Coronary Artery Risk Development in Young Adults (CARDIA) was initiated to investigate life-style and other factors that influence, favorably and unfavorably, the evolution of coronary heart disease risk factors during young adulthood. After a year of planning and protocol development, 5,116 black and white women and men, age 18-30 years, were recruited and examined in four urban areas: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota, and Oakland, California. The initial examination included carefully standardized measurements of major risk factors as well as assessments of psychosocial, dietary, and exercise-related characteristics that might influence them, or that might be independent risk factors. This report presents the recruitment and examination methods as well as the mean levels of blood pressure, total plasma cholesterol, height, weight and body mass index, and the prevalence of cigarette smoking by age, sex, race and educational level. Compared to recent national samples, smoking is less prevalent in CARDIA participants, and weight tends to be greater. Cholesterol levels are representative and somewhat lower blood pressures in CARDIA are probably, at least in part, due to differences in measurement methods. Especially noteworthy among several differences in risk factor levels by demographic subgroup, were a higher body mass index among black than white women and much higher prevalence of cigarette smoking among persons with no more than a high school education than among those with more education.     

Massive macroglossia, amyloidosis and myeloma

A 74 year old man with light-chain myeloma developed amyloidosis with macroglossia after 10 years of therapy with alkylating agents. Over a 2-year period his tongue enlarged to persistently protrude from his mouth, inhibit his speech, interfere with normal swallowing and eventually threaten his airway. As a life-saving procedure the tumorous anterior two-thirds of the tongue was resected, with excellent primary healing. Within two weeks the patient's speech became comprehensible and his ability to eat returned to normal. Although rare in amyloidosis, massive macroglossia may occur and surgical correction is easily achieved.