Oral sodium clodronate induced osteonecrosis of the jaw in a patient with myeloma.

Bisphosphonate therapy has been shown to significantly reduce the incidence of skeletal complications in patients with myeloma. Several recent reports have described osteonecrosis of the jaw (ONJ) associated with bisphosphonates. These reports mainly demonstrate an association between ONJ and potent i.v. bisphosphonates. We report a case of ONJ in a patient with myeloma, who had only been treated with oral sodium clodronate. While the degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as clodronate, remains uncertain it would be prudent to consider carefully the indications for the use of these agents to minimise the risk of ONJ.

Nonlinear domain-wall velocity enhancement by spin-polarized electric current.

The interaction between a dc spin-polarized electric current and a magnetic domain wall in a Permalloy nanowire was studied by high-bandwidth scanning Kerr polarimetry. The full functional dependence of wall velocity on electric current and magnetic field is presented. With the pinning potential nulled by a field, current-induced velocity enhancements exceeded 35 m/s at a current density of approximately 6 x 10(11) A/m(2). This large enhancement, more than 10 times that found in pinning-dominated experiments, results in part from an interaction that is nonlinear in current and independent of current direction.

Longitudinal investigation of energy expenditure in infants with cystic fibrosis.

OBJECTIVE: To determine when energy expenditure becomes elevated in infants with cystic fibrosis (CF). DESIGN: Longitudinal studies of total energy expenditure (TEE) using doubly labeled water were conducted in infants identified with CF by newborn screening through the first year of life. SETTING: Hospital and community based studies in Denver, Colorado, USA and Cambridge, UK. RESULTS: Eight of the 12 infants enrolled had begun enzyme therapy but were clinically asymptomatic. Four of the 12 infants were heterozygous for the delta F508 mutation, however no difference was seen in TEE from the remaining homozygous infants. TEE was compared to control cohorts at 2, 6 and 12 months of age. There was no difference from the control groups in TEE/kg fat free mass (FFM)/day at 2 months. However, by 6 months of age TEE/kg FFM/day in infants with CF exceeded that of age-matched controls by 25% (P<0.001). This elevation in TEE continued at 12 months of age exceeding that of controls by 30% (P<0.05). CONCLUSIONS: These results indicate that infants with CF have increased energy needs by 6 months of age and that early diagnosis alone does not prevent the development of increased caloric requirements. These findings emphasize the need for close nutritional monitoring to prevent suboptimal growth during infancy in this population. SPONSORSHIP: This research was supported by grant number 5 MO1 RR00069, General Clinical Research Centers Program, National Center for Research Resources, NIH.

Surface-step-induced double magnetic switching of Fe on vicinal W(100).

Two-level magnetic switching of a bilayer epitaxial Fe film grown on a graded stepped W(100) surface is observed using the magneto-optic Kerr effect. Hysteresis loops produced by the film at a location on the curved W(100) surface corresponding to a vicinal angle of 6.4 degrees exhibit two abrupt jumps in magnetization following spin orientation perpendicular to the steps resulting from surface-step-induced anisotropy. The two-step process can be understood in terms of abrupt depinning of spins in two inequivalent microdomains associated with the stepped surface. The results suggest a new realm of ultrathin film micromagnetics in which characteristic dimensions of 20-30 A can play a dominant role.

Effect of pancreatic enzymes on zinc absorption in cystic fibrosis.

BACKGROUND: The trace metal zinc has a wide range of important physiologic roles. Indirect evidence suggests that fat malabsorption is associated with malabsorption of zinc. The objective of this study was to evaluate the effect of pancreatic enzyme replacement on zinc absorption in children and adolescents with cystic fibrosis. METHODS: Subjects were four boys and four girls ranging in age from 7 to 17 years of age. All were pancreatic insufficient. Stable isotope labels, 70Zn and 67Zn, were administered orally in divided doses on consecutive days with meals. Meals were identical on the first 2 study days. Subjects were randomized to have pancreatic enzyme replacement withheld on the first or second day. All fecal samples were collected quantitatively for 10 days after label administration and were analyzed individually for total zinc and isotopic enrichment using atomic absorption spectrophotometry and fast atom bombardment mass spectrometry, respectively. Fractional absorption of zinc was calculated from cumulative fecal excretion of unabsorbed label. RESULTS: Fractional absorption while receiving enzymes was 0.50 +/- 0.29 versus 0.38 +/- 0.24 while not taking enzymes (p = 0.05). CONCLUSIONS: These results indicate that fractional absorption of zinc is impaired by pancreatic insufficiency in patients with cystic fibrosis, and is improved by exocrine pancreatic enzyme replacement.

Enteral nutrition for patients with cystic fibrosis: comparison of a semi-elemental and nonelemental formula.

OBJECTIVE: To determine whether differences in tolerance and absorption of fat and nitrogen exist between a semi-elemental nutritional formula without enzyme replacement and a nonelemental formula with enzyme replacement. STUDY DESIGN: Sixteen patients (eight girls and eight boys) with cystic fibrosis, 4 to 20 years of age (12+/-1.3, mean +/- SEM), who were pancreatic insufficient completed two 6-day regimens of nocturnal continuous enteral feedings offered in random order. Forty-four percent of the total daily energy was consumed as enteral tube feedings, and the remaining oral dietary intake remained constant throughout the study. Seventy-two-hour fecal collections from each study period were analyzed for total fat, long-chain fatty acids (LCFAs), medium-chain fatty acids (MCFAs), and nitrogen. RESULTS: Fat absorption was 80.2%+/-2.9% and 82.3%+/-3.1% (p = 0.58) for the semi-elemental and nonelemental formulas, respectively. Similarly, the coefficient of absorption of LCFAs was 69.5%+/-4.5% and 79.6%+/-3.4% (p = 0.30) for the semi-elemental and nonelemental formulas. Malabsorption of MCFAs contributed minimally to total fat malabsorption. There was no difference between formulas for MCFA or for nitrogen absorption, 83.7%+/-1.9% and 87.4%+/-1.4%, p = 0.48. All patients tolerated all feedings, and weight gained was 1.8+/-0.3 kg with no difference in weight gain between the trials. CONCLUSION: A nonelemental formula, with enzyme replacement, is absorbed as well as a predigested formula in patients with CF who are pancreatic insufficient.

Dietary substitution of medium chain triglycerides in subjects with non-insulin-dependent diabetes mellitus in an ambulatory setting: impact on glycemic control and insulin-mediated glucose metabolism.

OBJECTIVE: We have previously shown in an acute inpatient setting that dietary substitution of 77.5% of fat kcal as medium chain triglycerides (MCT) increased insulin-mediated glucose metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM), and that this effect appeared to be mediated by increases in insulin-mediated glucose disposal. The purpose of this study was to test the application of dietary substitution of medium chain triglycerides as an adjunctive tool in ambulatory therapy of NIDDM. METHODS: Five subjects with NIDDM underwent a baseline 6 hour insulin/glucose euglycemic clamp study, with simultaneous 3H-glucose infusion for calculation of glucose disposal rate and hepatic glucose output. Subjects were then randomized to begin one of two 30-day experimental diets, with long chain (LCT) or medium chain triglycerides (MCT), and subsequent crossover to the other diet. A 6 hour euglycemic clamp was repeated after each diet phase. RESULTS: Diet records and urinary organic acid excretion indicated a high level of dietary compliance by the study participants. Postprandial blood glucose excursions were less after one month on the diet with MCT than after the LCT diet (p = 0.004). However, fasting serum glucose, serum fructosamine (a measure of glycemia), fasting insulin, hepatic glucose output, and insulin-mediated glucose metabolism were not improved by the dietary substitution of MCT. CONCLUSION: These data indicate that supplementation of a tolerable amount of MCT in a conventional diabetic exchange diet has little impact on glycemic control in subjects with NIDDM in an ambulatory setting.

Macronutrient regulation of lipoprotein lipase is posttranslational.

To examine the relative impact of diet and meal composition on lipoprotein lipase (LPL), high fat (60% of energy) (HF) and high carbohydrate (68%) (HC) diets were fed to Sprague-Dawley rats for 2-3 wk, followed by overnight food deprivation and a meal of the same composition. Heparin-releasable LPL activities, mass and mRNA were measured in heart, diaphragm and soleus muscle and epididymal fat after food deprivation and 1, 2, 4 and 8 h postprandially. No effect of dietary macronutrient composition on LPL activity, protein or mRNA in food-deprived rats was demonstrated. However, in cardiac and diaphragm muscle, heparin-releasable LPL activity was suppressed by HC but stimulated by HF meal-feeding at 4 h. Moreover, in adipose tissue, the HC meal increased LPL activity at 1, 2 and 4 h relative to the basal period. Although there were no consistent effects of meal composition on LPL mass or mRNA in any one tissue, overall LPL mass was generally increased by HC meal-feeding. Because there were meal composition-dependent differences in LPL activity but no detectable differences in mass or mRNA in a particular tissue, LPL regulation by meals seems to be predominantly posttranslational.

Osteonecrosis following treatment for Hodgkin's disease.

Osteonecrosis is usually considered to be a minor and rare late sequelae of treatment for Hodgkin's Disease (HD). However, over ten years six patients out of a total of 53 patients treated for HD at the haematology department of a district general hospital developed osteonecrosis, an incidence of 11.3%. Routine isotope bone scanning of patients produced two further asymptomatic cases. These results suggest a higher incidence than previously suspected of a problem which caused our patients considerable morbidity. Further measures are required to identify and adequately treat a significant cause of late morbidity following chemotherapy for HD.

Idarubicin for remission induction of acute myeloid leukemia: United Kingdom multicenter experience.

Ninety-eight adult patients with acute myeloid leukemia were given variable remission induction/consolidation regimens containing idarubicin. Sixty-nine (70%) were new cases (median age, 56 years) and 29 (30%) were in relapse (n = 24) or had primary refractory disease (n = 5) (median age, 46 years). Complete remission (CR) rates were 57% (39 of 69 patients) of the newly diagnosed patients, with no difference for those below or above 55 years of age (56% v 59%) or for patients exhibiting white blood cell counts of less or more than 50 x 10(9)/L (52% v 69%; P = .8). Of the 39 patients who achieved CR, 26 (67%, 38% of the total number of patients) remain in CR with a median follow-up of 3 months (range, 0 to 61 months). Forty-two percent of the relapsed cases (10 of 24 patients) and 60% of the primary refractory disease cases (three of five patients) achieved CR. Of these 13 responders, six are alive (three continuing in CR and three relapsed) with a median follow-up of 3 months (range, 1 to 20 months), and seven have died with a median survival of 7 months (range, 0 to 12 months). Of the 52 patients who have achieved CR, 84% did so with one course of treatment and 16% with two courses. The presence of normal cytogenetic analysis or favorable chromosomal aberrations significantly improved overall CR rates. The patients in this study had significantly more unfavorable cytogenetic abnormalities than the historic controls. Reported toxicity was hepatic in 13%, cardiac in 9%, and renal in 7% of all cases. These data suggest a comparable efficacy of idarubicin to other anthracyclines in remission induction of acute myeloid leukemia, with a promising role in relapsed/refractory disease.

Autonomic dysfunction in severe tetanus: magnesium sulfate as an adjunct to deep sedation.

We studied the use of continuous iv magnesium (Mg) infusion to control the sympathetic crises in a patient with severe tetanus characterized by pronounced autonomic nervous system instability. Our results suggested that Mg is a useful adjunct to the CNS depressants traditionally used. This therapy controlled the sympathetic crises and also suppressed the release of catecholamines, although Mg infusions alone appeared to be inadequate therapy.

Co-incidental Von Willebrands disease and immune thrombocytopenia in pregnancy: treatment with high dose intravenous immunoglobulin.

We report a rare association of Von Willebrands disease and idiopathic immune thrombocytopenia in pregnancy. The major threat to the successful outcome of the pregnancy was posed by the acquired disorder. The use of high dose immunoglobulin allowed a normal delivery, without any adverse effects on mother or child.

Maintenance control of oral anticoagulant therapy by an automated chromogenic substrate assay of factor X.

An amidolytic assay of factor X based on the new chromogenic peptide substrate S 2337 (Kabi Diagnostica) was adapted for use with the Kem-o-Mat (Coulter Electronics) automated substrate analyser. Factor X was assayed in 25 healthy controls and in 375 patients on Warfarin therapy. The results in the control group correlated well with a one stage coagulation factor X assay. A good correlation was also found when the S 2337 factor X assay was compared with Thrombotest (Nyegaard & Co.) results in the patients. From the regression line of the S 2337 factor X assay on the Thrombotest results, the comparable range for factor X amidolytic activity in well controlled anticoagulated patients was found to be 22.5-37.5% with this method. Concordant classification of patients by both tests according to proposed therapeutic ranges demonstrated fully concordant information in 76% and fully discordant information in none. This study demonstrates that chromogenic substrate assays for anticoagulant control can be readily automated. Amidolytic assays of factor X based on the S 2337 substrate, therefore, warrant further clinical investigation as a potential method for controlling maintenance oral anticoagulant therapy.