A trial of Biolite ventilation tubes in children: is further use warranted?

A prospective controlled pilot study was undertaken in which Biolite (carbon-coated) ventilation tubes were placed in 44 ears and a conventional silicone tube in the contralateral ear. Long-term follow-up of these patients has revealed little difference in the incidence of tube occlusion or early extrusion. In addition, there were several disadvantages noted with the Biolite tubes: incomplete coating of the tube (especially within the lumen), shedding of the Biolite coating over time, "tattooing" of the tympanic membrane, poor otoscopic visibility, and the higher cost of these tubes. Since the Biolite tube has no documented advantages and, actually, several disadvantages, we believe its use in the treatment of middle ear disorders should be discontinued until significant benefits are demonstrated and present deficiencies are corrected.     

Pharmacist monitoring of parenteral nutrition: clinical and cost effectiveness.

The effect of pharmacist involvement in total parenteral nutrient (TPN) therapy on patient outcome and cost of therapy was studied. Data from 26 patients who received standard TPN solutions without pharmacist monitoring (Group 1) were compared with those from 26 patients whose TPN therapy was individualized (by use of a minicomputer) and monitored by a pharmacist (Group 2). Six patients from each group who were 35 days of age or younger and who received TPN as the only caloric source for 8 to 20 days were compared for clinical response. Mean duration of TPN therapy increased form 12.3 +/- 9 days for Group 1 to 14.8 +/- 12 days for Group 2, and the TPN use rate for Group 2 was 31% above that for group 1. The mean daily charge for TPN was greater for Group 1 ($72.00) than for Group 2 ($50.18). The pharmacy's mean cost per course of TPN for Group 2 was $44.10 less than that for Group 1. The mean weight gain in Group 1 was significantly less (4 g/day) than that in Group 2 (17 g/day) (p less than 0.05) (for the six patients per group compared). Pharmacist monitoring of TPN reduced the pharmacy's costs and patient charges for TPN and improved the patients' clinical responses to TPN.     

Hinged external fixation of the elbow: optimal axis alignment to minimize motion resistance

OBJECTIVE: To establish an optimal single hinge axis position for application of hinged external fixation to the elbow joint. DESIGN: Cadaveric biomechanical investigation. SETTING: A customized motion transducer applied passive elbow motion to six cadaveric upper extremities. The instant rotation axis of the humero-ulnar articulation was determined from three-dimensional kinematic data acquired by an electromagnetic motion tracking system. For each specimen, an optimal fixator hinge position was calculated from these motion data. INTERVENTION: A prototype articulated external fixator was applied to the elbow, first with its hinge aligned along the computed optimal position. Then the fixator was mounted in sixteen distinct off-axis positions. MAIN OUTCOME MEASURE: Additional resistance to joint motion (in terms of energy) corresponding to deliberately introduced amounts of relative malalignment between the optimal elbow axis and the actual fixator hinge axis. RESULTS: Aligning the fixator hinge along the optimized axis position resulted in a minimal amount of energy (0.15 joules) needed to rotate the elbow through a prescribed range of motion. Malpositioning the hinge by ten millimeters caused up to ten times that amount of motion resistance. CONCLUSIONS: An optimal fixator hinge position can be determined to minimize the increase in motion resistance due to fixator application. The severely increased motion resistance associated with small amounts of malalignment between the fixator hinge and the anatomic elbow axis suggests the need for highly accurate fixator hinge application.     

Alteration in urinary matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio predicts recurrence in nonmuscle-invasive bladder cancer.

PURPOSE: The purpose is to assess the prognostic significance of matrix metalloproteinase (MMP)-9 in patients with bladder cancer using a combination of ELISA (to measure MMP-9 in voided urine) and immunohistochemistry (to study MMP-9 in bladder tumors). The relationship between MMP-9 and its principal inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1 (in voided urine samples) was also studied. EXPERIMENTAL DESIGN: A total of 134 patients with bladder tumors (7 cis, 76 T(a), 27 T(1), 24 T(2)-T(4); 40 G1, 43 G2, and 44 G3), 33 patients with benign urological conditions, and 36 healthy volunteers was studied. Samples from 106 patients with bladder cancer and 12 controls were stained for MMP-9. Clinical follow-up data were available on 116 patients (median: 25 months; range: 4-36 months). RESULTS: MMP-9 was present in all urine samples analyzed. There were no differences between patients with cancer and patients with benign disorders. However, patients had significantly higher urinary MMP-9 than normal volunteers (P = 0.0167). Urinary MMP-9 was associated with bladder tumors of advanced stage (P = 0.0065) and large size (P < 0.0001) but not with grade (P = 0.14), multiplicity (P = 0.31), recurrence (P = 0.55), progression (P = 0.83), or survival (P = 0.55). Low MMP-9:TIMP-1 ratios in patients with nonmuscle-invasive tumors were associated with higher recurrence rates (P = 0.0035). Sixty percent (64 of 106) of bladder tumor specimens expressed MMP-9 compared with none of 12 normal urothelial biopsies (P < 0.0001). MMP-9 staining was associated with tumor size (P = 0.014), disease progression (P = 0.005), and poor disease-specific survival (P = 0.022) but was unrelated to tumor stage (P = 0.46), grade (P = 0.26), multiplicity (P = 0.85), or recurrence rate (P = 0.62). CONCLUSIONS: High urinary MMP-9 levels are associated with large bladder tumors. A low urinary MMP-9:TIMP-1 ratio may indicate a higher risk of intraluminal nonmuscle-invasive tumor recurrence and may assist in planning follow-up surveillance protocols.     

Clinicians' abilities to estimate cardiac index in ventilated children and infants

OBJECTIVES—To evaluate the ability of clinicians involved in the provision of paediatric intensive care to estimate cardiac index in ventilated children, based on physical examination and clinical and bedside laboratory data.METHODS—Clinicians were exposed to all available haemodynamic and laboratory data for each patient, allowed to make a physical examination, and asked to first categorise cardiac index as high, high to normal, low to normal, or low, and then to quantify this further with a numerical estimate. Cardiac index was measured simultaneously by femoral artery thermodilution (coefficient of variation 5.37%). One hundred and twelve estimates were made by 27 clinicians on 36 patients (median age 34.5months).RESULTS—Measured cardiac index ranged from 1.39 to 6.84 l/min/m². Overall, there was poor correlation categorically (κ statistic 0.09,weighted κ 0.169) and numerically (r = 0.24, 95% confidence interval 0.06 to 0.41 ), although some variation was seen among the various levels of seniority. CONCLUSION—Assuming that objective measurement, and hence manipulation, of haemodynamic variables may improve outcome, these findings support the need for a safe, accurate, and repeatable technique for measurement of cardiac index in children who are critically ill.     

Loss of heterozygosity at chromosome 9p in ductal carcinoma in situ and invasive carcinoma of the breast.

Twenty-three cases of ductal carcinoma in situ (DCIS), ten of which had an associated invasive component, were studied for loss of heterozygosity (LOH) of microsatellite markers on chromosome 9p and the results compared with a panel of 20 invasive breast carcinomas. In addition to the gene encoding p16, chromosome 9p is also thought to contain other putative tumour-suppressor genes. If the three panels of breast tumours showed LOH of markers in this region this would suggest that such putative genes were important in breast carcinogenesis. By studying both preinvasive and invasive breast tumours, it should also be possible to gain further information about the relationship between lesions of a different stage and to determine whether DCIS is indeed a precursor of invasive ductal carcinoma. Levels of LOH were low in the invasive-only set of tumours. Surprisingly, considerably higher levels of loss were observed in the tumours with an in situ component. Also, much heterogeneity was observed between different DCIS ducts or invasive tumour and DCIS from the same case.     

Low dose zolmitriptan as a 5-HT neuroendocrine challenge agent in humans

The 5-HT1B/D agonist sumatriptan has been used in a number of studies as a neuroendocrine challenge agent. Whether its neuroendocrine effects are centrally mediated is unclear, however, since sumatriptan shows minimal penetration of the central nervous system. Zolmitriptan shows a greater penetration into the central nervous system than sumatriptan, and has recently been shown to be an effective challenge agent. In order to determine the neuroendocrine, temperature and side effects of a 2.5 mg oral dose of zolmitriptan, 17 healthy volunteers underwent a placebo controlled, repeated measures, double blind neuroendocrine challenge. Zolmitriptan or placebo were administered, and cortisol, growth hormone, prolactin, blood pressure and temperature, were measured over four hours after the dose of zolmitriptan. Zolmitriptan at this dose was well tolerated by all subjects, with minimal side effects and only minor effects on blood pressure. There was a significant increase in serum growth hormone after zolmitriptan compared to placebo, however there were no significant effects on cortisol, prolactin or oral temperature. The neuroendocrine effects of 2.5 mg of orally administered zolmitriptan are similar to previously reported effects of sumatriptan, with minimal side effects.     

Contribution of individual projections alone and in combination for radiographic detection of ankle fractures

OBJECTIVE: We wanted to determine whether the standard three-view ankle radiographic series could be replaced by a two-view combination, and if so, which two-view combination (anteroposterior with lateral or mortise with lateral) would be superior. MATERIALS AND METHODS: During a 12-month period, we retrospectively reviewed 556 consecutive ankle radiographic studies consisting of anteroposterior, mortise, and lateral views. One hundred twenty patients with at least one ankle fracture were paired with 140 healthy control subjects. Each image in the three-view examination was separated and sorted by view and studied independently; all images were reviewed by two skeletal radiologists and two orthopedic surgeons. Each radiograph was evaluated for fracture of the medial, lateral, and posterior malleoli and the foot using a five-point confidence rating. Performance of each view and modeled two- and three-view combinations of views was evaluated with modified receiver operating characteristic analysis. RESULTS: The data provide little support for preferring either two-view combination (anteroposterior-lateral or mortise-lateral) for any type of fracture. The three-view combination does detect significantly more fractures than some two-view combinations in some locations, and there is a statistically significant cost in diagnostic accuracy for eliminating the anteroposterior or mortise view. CONCLUSION: Reducing the ankle radiographic series from three to two views would result in a small but significant decrease in the detection of fractures of the ankle and foot. Both two-view combinations are equivalent for fracture detection.     

Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel.

PURPOSE: To retrospectively evaluate the effects of six known allelic variants in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes on the pharmacokinetics of the anticancer agent paclitaxel (Taxol). EXPERIMENTAL DESIGN: A cohort of 97 Caucasian patients with cancer (median age, 57 years) received paclitaxel as an i.v. infusion (dose range, 80-225 mg/m(2)). Genomic DNA was analyzed using PCR RFLP or using Pyrosequencing. Pharmacokinetic variables for unbound paclitaxel were estimated using nonlinear mixed effect modeling. The effects of genotypes on typical value of clearance were evaluated with the likelihood ratio test within NONMEM. In addition, relations between genotype and individual pharmacokinetic variable estimates were evaluated with one-way ANOVA. RESULTS: The allele frequencies for the CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP3A4*3, CYP3A5*3C, and ABCB1 3435C>T variants were 0.7%, 9.2%, 2.1%, 0.5%, 93.2%, and 47.1%, respectively, and all were in Hardy-Weinberg equilibrium. The population typical value of clearance of unbound paclitaxel was 301 L/h (individual clearance range, 83.7-1055 L/h). The CYP2C8 or CYP3A4/5 genotypes were not statistically significantly associated with unbound clearance of paclitaxel. Likewise, no statistically significant association was observed between the ABCB1 3435C>T variant and any of the studied pharmacokinetic variables. CONCLUSIONS: This study indicates that the presently evaluated variant alleles in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes do not explain the substantial interindividual variability in paclitaxel pharmacokinetics.