Correction of metabolic acidosis and its effect on albumin in chronic hemodialysis patients

Serum albumin concentration has been strongly associated with risk of death in hemodialysis patients, with mortality increasing as albumin decreases. Metabolic acidosis stimulates protein catabolism and decreases protein synthesis. A study was undertaken to investigate the effect of increasing predialysis serum bicarbonate (HCO3) concentrations on the nutrition of hemodialysis patients as measured by albumin and total lymphocyte count (TLC). Metabolic acidosis was defined as a predialysis serum bicarbonate concentration of < or = 18 mEq/L. Thirty-six hemodialysis patients were enrolled in the study. Each had been stable on hemodialysis for > or = 3 months and each had a mean serum bicarbonate concentration of < or = 18 mEq/L on predialysis monthly laboratory values during the preceding 3 months. The subjects were randomized into 2 groups. The first group consisted of 18 control subjects who were dialyzed on a standard bicarbonate bath of 35 mEq/L. The second group consisted of 18 experimental patients who were dialyzed on a bicarbonate bath of 40 mEq/L. Subjects in the experimental group who had predialysis serum bicarbonate concentrations less than 22 mEq/L after 2 weeks on the higher bicarbonate bath were additionally supplemented with oral sodium bicarbonate at a dosage of 1 mEq/kg dry weight/d. Monthly predialysis laboratory values were checked for all subjects and included serum electrolytes, blood urea nitrogen, calcium, and albumin. TLCs were obtained at the initiation and at the conclusion of the study. Intact parathyroid hormone, blood pressures, and interdialytic weight gains were also followed. The study lasted 16 weeks; 32 subjects completed the study (16 in each group). There were no statistically significant differences between the two groups at the initiation of the study. The serum bicarbonate concentrations were significantly different between the two groups at the end of the study (control HCO3 17.3 +/- 3.2 mEq/L v experimental HCO3 20.2 +/- 2.9 mEq/L; P = 0.01). Serum albumin concentrations and TLCs were not statistically different (P > 0.05) between the two groups at the end of the study (control albumin 3.88 +/- 0.28 g/dL v experimental albumin 3.76 +/- 0.26 g/dL and control TLC 1,780.0 +/- 779.4/mm3 v experimental TLC 2,020.1 +/- 888.0/mm3). Potassium, intact parathyroid hormone, interdialytic weight gain, blood pressures, Kt/Vs, and protein catabolic rates did not differ. We found that the change in serum bicarbonate concentration was well-tolerated and was without any demonstrable side effects. We conclude that increasing the serum bicarbonate concentration by 3 mEq/L for 16 weeks has no effect on the indicators of nutrition that we measured (serum albumin and TLC).     

The vasa vasorum and angioplasty

Interruption of flow in the vasa vasorum may lead to medial necrosis and aneurysm formation. The purpose of this study was to determine whether angioplasty produces significant alterations in the morphology or blood flow of the vasa vasorum of the dilated artery. The morphology of the canine vasa vasorum was studied before and after angioplasty; in a separate experiment vessel wall blood flow (VWBF) in canine carotid arteries was measured after angioplasty to determine whether physiologic regulation of the blood flow was disrupted by arterial dilation. No morphologic changes could be demonstrated in the vasa vasorum of the dilated artery; however, VWBF was increased by 1194 +/- 215% (mean +/- standard error, p less than 0.01) between 90 and 120 minutes after angioplasty. VWBF in the adjacent nondilated arterial segment was also increased (720 +/- 177% between 10-30 minutes, p less than 0.01) but returned toward normal after 60 minutes. Adenosine caused a "paradoxical" decrease in VWBF (p less than 0.05) of the dilated arterial segment while causing increased VWBF (p less than 0.05) in the thoracic aorta. Angioplasty appears to produce persistent hyperemia in the dilated arterial wall. A paradoxical response to adenosine suggests that vasa vasorum in the dilated arterial segment are maximally vasodilated. This may be due to mechanical disruption of vasomotor tone or to release of vasoactive substances.     

Rizatriptan in the treatment of migraine

Migraine is a common, disabling disorder associated with considerable personal and societal burden. Current guidelines recommend triptans for the acute treatment of migraine unlikely to respond to less effective therapies. Rizatriptan is a second-generation triptan available in tablet or orally disintegrating tablet (wafer) formulations that offers several advantages over other members of its class. Rizatriptan is rapidly absorbed from the gastrointestinal tract and achieves maximum plasma concentrations more quickly than other triptans, providing rapid pain relief. Clinical trials have shown that rizatriptan is at least as effective or superior to other oral migraine-specific agents in the acute treatment of migraine, and has more consistent long-term efficacy across multiple migraine attacks. Rizatriptan has a favorable tolerability profile, and patients have reported greater satisfaction and a preference for rizatriptan over other migraine-specific agents. Improvements in quality of life reported with rizatriptan are consistent with its favorable efficacy and tolerability profiles. Notably, multi-attribute decision models that combine clinical data with patient- and physician-reported treatment preferences have identified rizatriptan as one of three triptans closest to a hypothetical “ideal”. The efficacy and tolerability of rizatriptan for the acute treatment of migraine have thus been well established.     

Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia

Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial.     

Congenital hypoplastic anemia inhibition of erythropoiesis by sera from patients with congenital hypoplastic anemia

An in vitro marrow culture assay designed to measure erythropoietic capability was used to ascertain the presence of an inhibitor in the sera of patients with congenital hypoplastic anemia (CHA). Marrow cells from nine anemic CHA patients responded to the stimulatory effect of exogenous erythropoietin (EPO) by an increase in heme synthesis in the presence of normal serum. The effect on heme synthesis was less than that observed with normal marrow cells. CHA serum inhibited heme synthesis by both normal and CHA marrow cells. It is concluded that an in-inhibitor of erythropoiesis is present in serum from CHA patients. This inhibitor most likely blocks the EPO-sensitive stem cell receptor sites, causing decreased response to the hormone.     

A clonally distinct recurrence of Burkitt's lymphoma at 15 years

A human immunodeficiency virus-negative male was successfully treated for two occurrences of Burkitt's lymphoma, 15 years apart. As consolidation of his second remission, he underwent high-dose chemotherapy with peripheral blood stem cell transplantation. In an effort to prove whether the second lymphoma was a relapse of the first or a second primary lymphoma, we obtained paraffin-embedded material from both lymphomas. DNA was extracted from this material and amplified by polymerase chain reaction (PCR) using consensus JH and VH region primers. Analysis of the PCR products, which mostly reflects VDJ joints, showed two sharp bands of different molecular size, proving the monoclonal nature of the lymphomas and suggesting that each had different Ig gene rearrangements. Sequencing of both PCR products showed a marked dissimilarity in nucleotide sequence in the clonally unique VDJ joint region, providing strong evidence for the separate cellular genesis of each lymphoma. These results suggest that late relapses of Burkitt's lymphoma should be examined for clonal distinctiveness. If the second lymphoma is distinct from the primary one, it might be treated as a primary lymphoma rather than as recurrent disease.