Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

A literature review of autograft and allograft anterior cruciate ligament reconstruction

Knee anterior cruciate ligament reconstructive surgery has significantly evolved and now includes the option of using an allograft. This has resulted in numerous studies evaluating the advantages and disadvantages of allografts. The purpose of this literature review is to evaluate this research and present important findings to allow the selection of the most appropriate graft source when considering allograft versus autograft reconstruction.     

Glomerular filtration rate and N-terminal pro-brain natriuretic peptide as predictors of cardiovascular mortality in vascular patients.

OBJECTIVES: The purpose of this work was to assess the prognostic role of glomerular filtration rate (GFR) and NT-terminal pro-B-type natriuretic peptide (NT-proBNP) for mortality end points in the vascular population. BACKGROUND: The GFR and NT-proBNP have been shown to predict mortality end points in free-living and limited vascular populations, independent of traditional risk factors. However, their prognostic power in an unrestricted vascular population is poorly understood. METHODS: A total of 412 subjects from a vascular cohort with a history of either peripheral arterial disease (PAD) and/or other cardiovascular disease (CVD) were included in this prospective cohort analysis and followed for an average of 6.7 years. Outcome variables were all-cause mortality, ischemic heart disease (IHD) mortality, and any cardiovascular mortality. The prognostic roles of GFR and NT-proBNP levels were determined using multivariate survival analysis. RESULTS: Higher GFR (per 10 ml/min/1.73 m2) was significantly protective for all-cause mortality (hazard ratio [HR] 0.81, p < 0.001), IHD mortality (HR 0.82, p = 0.008), and CVD mortality (HR 0.84, p = 0.005). Conversely, NT-proBNP was not a significant predictor of any mortality end point. The GFR showed the strongest association in subjects with a history of other CVD. Although NT-proBNP did not demonstrate a significant prognostic role in any of the subgroups, the data were suggestive for patients with PAD alone. CONCLUSIONS: Glomerular filtration rate was a robust predictor of all-cause, IHD, and cardiovascular mortality in the vascular population, particularly in those with a history of other CVD, while NT-proBNP showed a suggestive association limited to the group with PAD only. These findings suggest that these markers must be selectively applied in the vascular population for greatest clinical utility.     

A light-hearted look at a lion-hearted organ (or, a perspective from three standard deviations beyond the norm) Part 2 (of 2 parts)

Throughout history, the heart has been associated not only with its life-sustaining function but also with its close ties to the human emotions. In this literature and internet review, we attempt to gather and organize information from both of these perspectives as they relate to the heart in the following 11 categories: (1) fun facts, (2) medical photography, (3) history, (4) languages (etymology), (5) nonmedical English expressions, (6) death, (7) the arts, (8) movie titles, (9) song titles, (10) Shakespeare, and (11) the Bible. Part 1 (previously published) covered the first five topics, and Part 2 will cover the last six topics. These data may be useful to those who are engaged in teaching about the cardiovascular system.     

Percutaneous biopsy in evaluation of lung nodules.

Management of an indeterminate pulmonary nodule is a diagnostic challenge that commonly confronts primary care physicians and specialists. Patients often present with this radiographic finding in the course of an unrelated medical evaluation. We examined our institution's experience with percutaneous biopsy of lung nodules to determine the impact of this procedure on overall patient care. Although significant complications are uncommon, the expedience of percutaneous lung biopsy often supplants a surgical opinion prior to initiation of therapy without added diagnostic benefit or cost-savings. Hence, we caution practitioners to use this technique as an adjunct to diagnosis and not a substitute for multidisciplinary care.     

Case-control study of the alpha-synuclein interacting protein gene and Parkinson's disease.

We conducted a case-control study of the alpha-synuclein-interacting protein gene (SNCAIP, also known as synphilin-1) and Parkinson's disease (PD). A total of 319 PD cases and 195 controls were genotyped for four SNCAIP variants, including a microsatellite repeat in intron 4 and three restriction fragment length polymorphisms (RFLP) proximal to the 5' terminal of exons 1, 4, and 6. None of the variants were found associated with PD overall. Global score statistics were not significant for four, three, and two loci haplotypes. All four loci were in linkage disequilibrium for cases, controls, or both groups combined (P < 0.0001). Recursive partitioning showed no interactions between variants of the SNCAIP gene and variants of the alpha-synuclein gene (SNCA) or the parkin (PARK2) gene.     

Red blood cell methotrexate and folate levels in children with acute lymphoblastic leukemia undergoing therapy: a Pediatric Oncology Group pilot study

Summary We enrolled children with acute lymphoblastic leukemia (ALL) in a Pediatric Oncology Group (POG) pilot study to monitor erythrocyte (RBC) methotrexate (MTX) and folate (F) levels before and during treatment. The mean value for RBCF at diagnosis was 0.86±0.46 nmol/ml RBC in the 214 patients who achieved remission and 1.21±0.74 nmol/ml RBC in the 10 patients who did not (P=0.020). Folate levels tended to increase during remission induction, but they dropped following an intensive consolidation with methotrexate to levels that were sustained throughout chemotherapy treatment. Methotrexate levels reached mean values of approximately 0.15 nmol/ml RBC at the end of an intensive methotrexate consolidation, then fell to levels that were sustained throughout maintenance therapy. There was a weak correlation between improved event-free survival and higher RBCMTX levels after consolidation, but no correlation was found between improved survival and the level of RBCMTX or RBCF during maintenance therapy. A larger study with more complete data is needed to determine whether RBCMTX or RBCF might be useful in predicting event-free survival in patients with ALL.This work was supported in part by grants from the National Cancer Institute and the National Institute of Health (CA-30969, CA-28476, CA29139, CA-159-89, and CA-33587)     

A Comparative Study of the Percutaneous versus Intraoral Technique for Mental Nerve Block

Objective: Mental nerve block is frequently used to aid repair of facial lacerations; both percutaneous and intraoral approaches to blocking this nerve are used, but have never been compared. The authors compared the two techniques for pain of administration and effectiveness of anesthesia. Methods: A prospective, randomized, single-blind, crossover study was conducted using ten healthy volunteers aged 22 to 33 years. Patients having prior experience with mental nerve blocks, lidocaine allergy, active oral/facial infection, or previous facial fractures were excluded. Bilateral mental nerve blocks were done using intraoral technique on one side and percutaneous technique on the other. Both techniques were used by the same investigator and were carried out with 27-gauge needles and 2.5 mL of 2% buffered lidocaine at room temperature injected over 20 seconds. The oral mucosa was topically anesthetized with viscous lidocaine for 1 minute prior to intraoral injection. The orders of the blocks and sides of the face anesthetized were randomized. Subjective and objective pain (visual-analog scale), efficacy (anesthesia of lower lip), time to onset, and duration of anesthesia were evaluated. Results: The intraoral technique was subjectively less painful than the percutaneous approach in nine of ten subjects (p = 0.02). Scores on the visual-analog pain scale were significantly lower for the intraoral technique (p = 0.03). Intraoral injection produced lower-lip anesthesia in 10/10 subjects versus 7/10 for percutaneous (p = 0.25). Times to onset (approximately 1–2 minutes) and durations of anesthesia (approximately one hour) were similar for the two techniques. Conclusion: The intraoral approach to the mental nerve block with adjunctive topical anesthesia was subjectively and objectively less painful than the percutaneous approach without adjunctive anesthesia. While the intraoral approach had a greater efficacy of lower-lip anesthesia and a longer duration of action, these differences were not statistically significant.