Increased serum vitamin A and E levels after lung transplantation.

BACKGROUND: Adult cystic fibrosis (CF) patients experience significant increases in serum vitamin A and E levels after lung transplantation. It is unclear whether this finding is specific to the CF population or inherent to the lung transplantation process. METHODS: The objectives of this study were to assess pre- and postlung transplantation serum vitamin A and E levels in subjects with end-stage lung disease secondary to all causes. The study population consisted of adults who received a lung transplant at the Toronto Lung Transplant Program between 2004 and 2009. The mean change in serum vitamin A and E levels pre- and postlung transplant was evaluated using a paired t test, while differences in vitamin A and E levels between CF and non-CF subjects were determined using a Student's t test. RESULTS: Thirty-two CF and 21 non-CF subjects who underwent lung transplantation were included in the study. Mean serum vitamin A and vitamin E levels increased significantly after transplant, from 1.2 to 3.5 µmol/L (P<0.0001) and from 21.9 to 33.2 µmol/L (P<0.0001), respectively. The proportion of individuals with serum levels above the upper limit of normal increased from 7.6% to 88.7% (P<0.0001) and from 11.3% to 24.5% (P=0.02) for vitamin A and vitamin E, respectively. The dosage of vitamin supplementation did not increase after transplant. CONCLUSIONS: Significant increases in serum vitamin A and E levels were seen in both CF and non-CF subjects after lung transplantation. Further research is needed to understand the cause and clinical implications of these findings.

The association between acetaminophen concentrations in the cerebrospinal fluid and temperature decline in febrile infants.

The objective of this study consisting of a prospective cohort of febrile infants was to describe the correlation between cerebrospinal fluid (CSF) acetaminophen (paracetamol) concentrations and changes in body temperature in febrile infants. Infants, one week to one year of age, with rectal temperature >or=38.0 degrees C, treated with acetaminophen were studied if they underwent a lumbar puncture (LP). Patients received 15 mg/kg of acetaminophen 30 minutes to 4 hours before lumbar puncture was performed. Rectal temperature was documented before acetaminophen administration and at the time of lumbar puncture. Plasma and CSF acetaminophen levels were determined using high-pressure liquid chromatography. Thirty-one infants were studied. In a nonlinear regression, the relationship among acetaminophen concentrations in the CSF, time, and temperature differences is best described by a Lorentzian distribution. The model suggests that a peak effect on temperature is achieved at CSF concentration of 11.9 microg/mL and 182 minutes after acetaminophen administration (P<0.001 and P<0.001, respectively r=0.9 adjusted r square=0.78). Temperature decrement in young febrile infants, treated with acetaminophen, correlates with time and acetaminophen concentrations in the CSF. High concentrations of acetaminophen in the CSF, exceeding a certain level, are not associated with greater temperature decrement.

Generalized seizures following topical lidocaine administration during circumcision: establishing causation.

We report a case of neonatal seizures after lidocaine administration for circumcision. A 3-month-old male infant received an overdose as evidenced by toxic lidocaine levels and developed generalized seizures shortly after. Back extrapolation of the serum lidocaine concentration to time zero was used to determine the administered dose. The Naranjo scale was used to determine causation; probable causation was defined. Particular care must be taken to administer an appropriate dose of local anesthetics in infants to avoid life-threatening seizures.

Breast-feeding during maternal use of azathioprine.

OBJECTIVE: To report the clinical outcome of infants whose mothers were taking azathioprine while nursing and to quantify the transfer of 6-mercaptopurine (6-MP), its active metabolite, into breast milk. CASE SUMMARY: We report on a series of 4 patients treated with azathioprine while lactating. Breast milk samples were analyzed for 6-MP in 2 of the mothers. Several milk samples per patient were analyzed; levels of 6-MP were undetectable by high performance liquid chromatography (limit of detection 5 ng/mL). Therefore, the absolute relative infant dose would have been less than 0.09% of the maternal weight-adjusted dose. No adverse effects were encountered in any of the 4 infants. DISCUSSION: A large number of women of reproductive age are treated with azathioprine for a range of chronic conditions that require immunosuppression, such as systemic lupus erythematosus or solid organ transplants. Similar to other antimetabolites, the drug has generally been contraindicated for use during breast-feeding because of the theoretical concern for toxicity in the nursing infant. The available literature in this area is sparse and dated. The data presented here confirm published reports of minimal 6-MP excretion into milk, suggesting that significant systemic adverse effects in the infant are unlikely. CONCLUSIONS: Maternal azathioprine use during lactation does not appear to pose a significant immediate clinical risk to the suckling infant. Continued monitoring and long-term assessment of these infants are warranted.

Increased vitamin A and E levels in adult cystic fibrosis patients after lung transplantation.

Most patients with cystic fibrosis (CF) and pancreatic insufficiency require supplementation with fat-soluble vitamins to maintain normal serum levels. Even with supplementation, toxicity is rare. We evaluated serum vitamin A and E levels in 23 adult patients with CF who underwent double lung transplantation. Twenty-one of the subjects were pancreatic insufficient. Fifteen subjects had serum vitamin levels before and after transplant. The median time posttransplantation for these subjects was 9 months. Mean serum vitamin A and E levels were significantly higher posttransplantation (P<0.0001, P<0.001, respectively). Eight subjects who only had posttransplant vitamin levels also had abnormally high vitamin A levels. Although the etiology of this novel finding is unclear, possibilities include altered absorption, drug interactions, impaired retinol metabolism, or increased hepatic synthesis of retinol binding protein.

Cyclosporine excretion into breast milk.

Although many female patients of childbearing age who are receiving cyclosporine have successful pregnancies, these women may be advised not to breast-feed. During recent years, cases of uneventful pregnancies and subsequent successful breast-feeding have been reported in the literature. The infant's blood cyclosporine concentration was usually very low. Based on these findings and the lack of detectable adverse effects, some investigators have suggested that women on cyclosporine may breast-feed, challenging the conventional view that cyclosporine is contraindicated during breast-feeding. Here, we report our experience with cyclosporine use during breast-feeding in five mother-infant pairs. We show a wide range of infant exposures to the drug in milk, noting that one of the infants had therapeutic blood concentrations of cyclosporine despite relatively low concentrations of the drug in milk.

Analytical evaluation of hemoglobin A(1c) dual kit assay on Bio-Rad Variant II: an automated HPLC hemoglobin analyzer for the management of diabetic patients.

OBJECTIVES: To evaluate the analytical performance of the Bio-Rad Variant II HbA(1c) dual kit assay. DESIGN AND METHODS: Precision, carryover, linearity and analytical range were investigated. 139 patients' HbA(1c) results analyzed by the Variant II were compared to the Variant I method. 49 blood samples analyzed by the Variant II at Toronto Medical Laboratories (TML) were compared to the Variant II at Hospital for Sick Children (HSC). RESULTS: Total imprecision was less than 2% for the Variant II assay. The method had a wide analytical range with no carryover. HbA(1c) results were not changed after switching back and forth from the beta thalassemia to HbA(1c) assay. The Variant II showed an average of 0.0027 negative bias compared to the Variant I method. There was an average of 0.0020 negative bias for HbA(1c) results on the Variant II at TML compared to the Variant II at HSC. CONCLUSIONS: HbA(1c) analysis on the Variant II HbA(1c) dual kit is a relatively fast and reproducible method.

Glycine conjugation of para-aminobenzoic acid (PABA): a pilot study of a novel prognostic test in acute liver failure in children.

BACKGROUND: Fulminant hepatic failure (FHF) is associated with high mortality; few patients survive without liver transplantation. It is important to have a sensitive, specific early predictor of outcome to distinguish potential survivors (S) from nonsurvivors (NS). OBJECTIVE: Because we had previously shown that glycine conjugation of para-aminobenzoic acid (PABA) quantitatively reflects liver function in children with chronic liver disease, in this pilot study we wanted to determine whether the measurement of the glycine conjugates of PABA could distinguish S from NS in FHF in comparison with standard prognostic indices. METHODS: Twenty-four patients were studied: acute severe hepatitis (n = 7), subfulminant hepatic failure (n = 7), and FHF (n = 10). Assessment of King's College criteria, measurement of factor V and VII levels, PABA testing, and transjugular liver biopsies were performed in almost all patients within 48 hours of admission. Serum PABA and its glycine conjugates (para-aminohippurate (PAHA) and para-acetamidohippurate (PAAHA)) were measured thirty minutes after oral administration by high-pressure liquid chromatography. Poor prognostic categories as previously established in the literature were defined as factor V < 0.20U/ml, factor VII < 0.08 U/ml, % necrosis >70%, hippurate ratio = 0%, and PAHA = 0M. RESULTS: The measurement of PAHA was the best predictor of a poor outcome in patients with acute liver failure with a sensitivity of 92%, and negative predictive value (NPV) of 92% compared with a sensitivity of 54% and a NPV of 63% with King's College criteria. CONCLUSION: Measurement of serum PAHA is the best early prognostic marker of death in children who suffer from FHF.

How high can we go with phenytoin?

Phenytoin is an effective anticonvulsant, but high serum phenytoin concentrations may be associated with serious toxicity. The upper limit for the therapeutic serum concentration of phenytoin is considered to be 80 micromol/L. However, in some situations higher serum concentrations are needed to control seizures. The authors describe a 9-year-old girl who needed concentrations twice the normal amount to control recurrent episodes of decreased levels of consciousness. Except for nystagmus, she had no other signs of phenytoin toxicity. This patient highlights the critical principle in therapeutic drug monitoring of individualizing drug therapy. Although some patients receiving phenytoin may achieve seizure control with "subtherapeutic" levels (i.e., <40 micromol/L), others may need supratherapeutic levels, as was the case with this patient. Clinicians should be careful not to treat "numbers" (i.e., serum concentrations), but rather the patient's clinical condition, with a careful balance between therapeutic advantage and adverse effects.