Lanthanum carbonate vs. sevelamer hydrochloride for the reduction of serum phosphorus in hemodialysis patients: a crossover study.

AIMS: The aim of this crossover study was to compare the reduction of serum phosphorus (SP) with fixed doses of the non-calcium-containing phosphate binders lanthanum carbonate (LC) and sevelamer hydrochloride (SH) in hemodialysis patients. METHODS: Following washout (2 - 3 weeks), 182 patients with SP >or= 6.0 mg/dl and calcium >or= 8.4 mg/dl were randomized (1:1) to receive LC (2,250 to 3,000 mg/day) or SH (4,800 to 6,400 mg/day) for 4 weeks. Patients underwent a second washout (2 weeks) and switched to the alternative binder for 4 weeks. RESULTS: At the end of treatment, LC had reduced SP by 1.7 +/- 0.1 mg/dl, compared with 1.4 +/- 0.1 mg/dl for SH; the difference was not statistically significant in the primary analysis (LOCF, p = 0.133). However, the reduction with LC was significantly greater than with SH in a prespecified key secondary analysis of patients who completed 4 weeks of treatment with each binder (0.5 mg/dl difference, p = 0.007). The reduction of SP was also greater with LC than SH after 1 week of treatment (p = 0.024). CONCLUSIONS: Although the primary analysis found no difference between LC and SH in the reduction of SP, a significant difference in favor of LC was observed in patients who completed treatment. The results of this study show interesting trends with respect to onset and duration of action that warrant further investigation in longer-term studies.

Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas.

We examined the effect of preoperative chemoradiotherapy on the ability to obtain pathologically negative resection margins in patients undergoing pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas. Between 1987 and 2000, 100 patients underwent Whipple resection with curative intent for primary adenocarcinoma of the head of the pancreas. Pathologic assessment of six margins (proximal and distal superior mesenteric artery, proximal and distal superior mesenteric vein, pancreas, retroperitoneum, common bile duct, and hepatic artery) was undertaken by either frozen section (pancreas and common duct) or permanent section. A margin was considered positive if tumor was present less than 1 mm from the inked specimen. Margins noted to be positive on frozen section were resected whenever possible. Of the 100 patients treated, 47 (47%) underwent postoperative radiation and chemotherapy (group I) and 53 (53%) received preoperative chemoradiotherapy (group II) with either 5-fluorouracil (32 patients) or gemcitabine (21 patients). Patient demographics and operative parameters were similar in the two groups, with the exception of preoperative tumor size (CT scan), which was greater in group II (P < 0.001), and number of previous operations, which was greater in group II (P < 0.0001). Statistical analysis of the number of negative surgical margins clear of tumor was performed using Fisher's exact test. All patients (100%) had six margins assessed for microscopic involvement with tumor. In the preoperative therapy group, 5 (7.5%) of 53 patients had more than one positive margin, whereas 21 (44.7%) of 47 patients without preoperative therapy had more than one margin with disease extension (P < 0.001). Additionally, only 11 (25.6%) of the 47 patients without preoperative therapy had six negative margins vs. 27 (50.9%) of 53 in the group receiving preoperative therapy (P = 0.013). Survival analysis reveals a significant increase in survival in margin-negative patients (P = 0.02). Similarly, a strong trend toward improved disease-free and overall survival is seen in patients with a single positive margin vs. multiple margins. Overall, we find a negative impact on survival with an increasing number of positive margins (P = 0.025, hazard ratio 1.3). When stratified for individual margin status, survival was decreased in patients with positive superior mesenteric artery (P = 0.06) and vein (P = 0.04) margins. However, this has not yet resulted in a significant increase in disease-free or overall survival for patients receiving preoperative therapy (P = 0.07).

Lead content of calcium supplements.

CONTEXT: Substantial quantities of lead have been reported in some over-the-counter calcium supplement preparations, including not only bone-meal and dolomite, but also over-the-counter natural and refined calcium carbonate formulations. Examination of this issue is warranted given recent increases in physician recommendations for calcium supplements for prevention and treatment of osteoporosis. OBJECTIVES: To determine the lead content of calcium supplements and to quantify the lead exposure from popular brands of calcium in dosages used for childhood recommended daily allowance, osteoporosis, and phosphate binding in dialysis patients. DESIGN AND SETTING: Analysis of lead content in 21 formulations of nonprescription calcium carbonate (including 7 natural [ie, oyster shell] and 14 refined), 1 brand of prescription-only calcium acetate, and 1 noncalcium synthetic phosphate binder conducted in March 2000. MAIN OUTCOME MEASURES: Lead content, assayed using electrothermal atomic absorption, expressed as micrograms of lead per 800 mg/d of elemental calcium, per 1500 mg/d of calcium, and for a range of dosages for patients with renal failure. Six microg/d of lead was considered the absolute dietary limit, with no more than 1 microg/d being the goal for supplements. RESULTS: Four of 7 natural products had measurable lead content, amounting to approximately 1 microg/d for 800 mg/d of calcium, between 1 and 2 microg/d for 1500 mg/d of calcium, and up to 10 microg/d for renal dosages. Four of the 14 refined products had similar lead content, including up to 3 microg/d of lead in osteoporosis calcium dosages and up to 20 microg/d in high renal dosages. No lead was detected in the calcium acetate or polymer products. Lead was present even in some brand name products from major pharmaceutical companies not of natural oyster shell derivation. CONCLUSIONS: Despite increasingly stringent limits of lead exposure, many calcium supplement formulations contain lead and thereby may pose an easily avoidable public health concern. JAMA. 2000;284:1425-1429.

Improved nutrition after the detection and treatment of occult gastroparesis in nondiabetic dialysis patients.

Malnutrition in dialysis patients is of multifactorial etiology and is associated with greatly increased morbidity and mortality. A low serum albumin level is one of the most powerful predictors of death and may persist despite optimization of the dialysis prescription. We retrospectively reviewed our experience in improving nutrition in nondiabetic patients with unexplained hypoalbuminemia. Using radionuclide solid-phase gastric emptying scans, we identified 6 patients who had occult gastroparesis. These patients (one on hemodialysis and five on peritoneal dialysis) were then treated with prokinetic medications (erythromycin elixir or metoclopramide) selected on the basis of their effectiveness in improving the scanning results after being given intravenously. Gastric emptying half-times improved from a median of 122 minutes (range, 95 to >300 minutes; normal, < or = 90 minutes) to 12 +/- 2 minutes (mean +/- SEM). The serum albumin increased from 3.3 +/- 0.04 g/dL to 3.7 +/- 0.08 g/dL at 3 months, with every patient's value higher than 3.5 g/dL. This improvement was statistically significant (P = 0.008) over the 5-month period of observation, which encompassed the 2 months before and 3 months after treatment. There was a linear improvement (P = 0.008) that showed a quadratic trend (P = 0.078) for a plateau at the final sampling point. The serum blood urea nitrogen, creatinine, and hematocrit levels remained unchanged (P > 0.1). We conclude that gastric emptying scans are valuable in identifying occult gastroparesis in high-risk patients and can guide the selection of prokinetic therapy, which may significantly increase serum albumin levels.

Screening for colorectal neoplasia: physicians' adherence to complete diagnostic evaluation.

This prospective study was done in a health maintenance organization colorectal cancer screening program to determine whether 166 persons found to have abnormal fecal occult blood test results typically underwent complete diagnostic evaluation (i.e., either colonoscopy or barium enema x-ray plus flexible sigmoidoscopy). Chart audit data show that 137 (82%) subjects contacted a physician to discuss follow-up. A complete diagnostic evaluation was recommended to only 52 (38%) patients who talked with a physician. Forty-two (81%) patients who were advised to get a complete diagnostic evaluation actually complied. Significant differences in clinical findings were observed for patients who did and did not have a complete diagnostic evaluation.

Effects of ascorbic acid and pyridoxine supplementation on oxalate metabolism in peritoneal dialysis patients.

We studied the effect of vitamin C and B6 supplementation on oxalate metabolism in seven patients receiving chronic peritoneal dialysis therapy. The study was divided into three phases, each lasting 4 weeks. Plasma oxalate, total ascorbic acid, and pyridoxal-5'-phosphate (PLP) were measured at the end of each phase. Twenty-four-hour urinary excretion and dialysate removal rates of oxalate were also obtained. At the end of phase I (supplement-free period), plasma oxalate levels were markedly elevated at 47.6 +/- 7.1 mumol/L (437 +/- 66 micrograms/dL) (normal, 3.4 +/- 0.4 mumol/L [30.3 +/- 1.6 micrograms/dL]). Plasma total ascorbic acid levels were 62 +/- 6 mumol/L (1.0 +/- 0.1 mg/dL) (normal, 45 to 57 mumol/L [0.8 to 1.0 mg/dL]), while plasma PLP levels were markedly reduced to 24 +/- 5 nmol/L (normal, 40 to 80 nmol/L). Daily supplements of 0.57 mmol (100 mg) ascorbic acid orally (phase II) resulted in a 19% increase in the plasma oxalate levels to 57.8 +/- 6.1 mumol/L (520 +/- 55 micrograms/dL) (P less than 0.03), with a concomitant 60% increase in the plasma ascorbate levels (91 +/- 6 mumol/L [1.6 +/- 0.1 mg/dL], P less than 0.01). Plasma PLP values remained low. Finally, during phase III (0.57 mmol or 100 mg ascorbic acid plus 59.6 mumol or 10 mg pyridoxine HCI orally daily), plasma oxalate levels declined by 17% to 47.9 +/- 5.2 mumol/L (431 +/- 47 micrograms/dL) (P greater than 0.05 v phase II).(ABSTRACT TRUNCATED AT 250 WORDS)

Ascorbic acid supplements in patients receiving chronic peritoneal dialysis.

Ascorbic acid supplements are commonly prescribed to patients with end-stage renal disease receiving peritoneal dialysis. To establish the need for ascorbic acid supplements, we evaluated seven chronic peritoneal dialysis patients during a supplement-free (phase I) period, and while receiving oral ascorbic acid (0.57 mmol/d [100 mg/d]) (phase II). Because of a proposed interaction with vitamin B6, patients were additionally supplemented with pyridoxine HCl (59.6 mumol/d [10 mg/d]) (phase III). Plasma levels and dialysate removal rates of total ascorbic acid and plasma pyridoxal-5-phosphate (PLP) were measured at the end of each phase. During phase I, plasma ascorbic acid levels (normal, 45 to 57 mumol/L [0.8 to 1.0 mg/dL]) declined slightly from 74 +/- 11 mumol/L (1.3 +/- 0.2 mg/dL) to 62 +/- 11 mumol/L (1.1 +/- 0.2 mg/dL) (P less than 0.02) at the end of the third week, and then remained stable to the end of the fourth week. Plasma ascorbic acid levels were no different in patients with or without residual renal function. With the addition of vitamin C supplements, plasma ascorbic acid levels increased by 45% of the baseline value at the end of phases II (P less than 0.001). The dialysate removal rate of ascorbic acid was 0.28 +/- 0.03 mmol/d (50 +/- 6 mg/d) at the end of phase I, and increased by 57% of the baseline value at the end of phases II (P less than 0.001). However, the peritoneal clearance of ascorbic acid remained unchanged during all phases the study. Pyridoxine depletion or repletion had no effect on plasma ascorbic acid levels (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Quality of well-being before and after antibiotic treatment of pulmonary exacerbation in patients with cystic fibrosis.

General quality of life has only recently been measured with an objective tool in patients with cystic fibrosis (CF), and there have been no reported attempts to document changes in patients' overall well-being over time, as patients deteriorate or respond to intervention. We applied the Quality of Well-Being scale (QWB) in 28 patients with CF before and after a two-week course of oral ciprofloxacin used to treat pulmonary exacerbations. There were significant correlations between changes in QWB and various pulmonary function test results; QWB vs FEV1: r = 0.4, p less than 0.03; QWB vs FVC: r = 0.5, p less than 0.01; and QWB vs SaO2: r = 0.4, p less than 0.05. Thus, the QWB can track changes in general well-being in CF patients over a brief time and detect changes associated with pulmonary exacerbation and its treatment.

Vitamin B6 requirements of patients on chronic peritoneal dialysis.

Patients with chronic renal failure often develop vitamin B6 deficiency, which is of clinical concern because the multiorgan system manifestations are similar to those of uremia. Vitamin B6 deficiency in hemodialysis patients has been previously studied, but the need for daily pyridoxine supplementation in patients on chronic peritoneal dialysis (CPD) remains unclear. Therefore, we studied a group of 11 stable patients, nine on CAPD and two CCPD, to test for vitamin B6 deficiency and to establish daily requirements. Adequacy of vitamin B6 nutrition was assessed by measurement of plasma and dialysate effluent total vitamin B6 and pyridoxal 5'-phosphate (PLP), the latter using a very sensitive modification of the tyrosine apodecarboxylase enzyme assay. After four weeks without vitamin B6 supplements on a diet containing 1.3 +/- 0.2 mg vitamin B6/day (7.7 +/- 1.2 mumol/day), all patients had subnormal plasma PLP levels, 16 +/- 3 nmol/liter (nml 40 to 60), seven having a severe deficiency (less than or equal to 20 nmol/liter). Plasma total vitamin B6 levels (which includes non-PLP forms of the vitamin) were normal in all patients at baseline, 116 +/- 29 nmol/liter. Peritoneal losses were small, 8 +/- 2 nmol PLP/day and 545 +/- 61 nmol total vitamin B6/day. Supplementation with 5 mg/day oral pyrodoxine HCl for up to 16 weeks adequately repleted eight patients (65 +/- 7 nmol PLP/L), while three patients required 10 mg/day to achieve normal plasma PLP levels. During three episodes of peritonitis, dialysate losses of PLP did not increase.(ABSTRACT TRUNCATED AT 250 WORDS)