Indomethacin and renal function in premature infants with persistent patent ductus arteriosus.

Renal function during indomethacin treatment was studied in 12 premature infants with patent ductus arteriosus. Decreases in urinary flow rate, GFR, and CH2O by 56, 27, and 66%, respectively, occurred during Indo therapy. Urinary excretion rates of ions were also reduced: Na by 70%, Cl by 79%, K by 40%. These changes were accompanied by slight decreases in plasma sodium concentration and osmolality. Except for GFR and urinary Na and osmolality, all these functions returned to pretreatment values one to two weeks after stopping the drug.     

The pharmacology of chewable versus regular carbamazepine in chronically treated children with epilepsy.

We report the first comparison of Chewable and Regular Carbamazepine (CBZ) tablets in children with epilepsy. Forty-four children receiving chronic monotherapy CBZ participated. In month 1 children received regular CBZ; in month 2, the same dose of Chewable CBZ. Once per week fasting predose CBZ and CBZ epoxide serum levels were determined. In a subset of 15 children, at the end of each month serum levels were obtained every 2 hours for 12 hours beginning pre-dose. Standards for CBZ and CBZ epoxide were tested in each centre. Overall, weekly levels showed no consistent differences between the month on chewable CBZ and regular CBZ. Seizure control and rates of reported side effects were similar. In five patients chewable CBZ produced higher peak CBZ levels while five had higher peaks with regular CBZ. In conclusion, regular and chewable CBZ often have unpredictable differences in peak but not trough levels of CBZ suggesting that peak level side effects with one form of CBZ might be alleviated by changing to the other.     

Simultaneous simple and fast quantification of three major immunosuppressants by liquid chromatography--tandem mass-spectrometry.

OBJECTIVES: The aim of the current study was to develop a simple, fast and universal method for quantification of any combination of the three major immunosuppressants sirolimus, tacrolimus and cyclosporin in whole blood, using a LC-tandem mass spectrometer (API-2000, SCIEX, Toronto, Canada). METHODS: 250 microL whole blood was spiked with internal standard (ritonavir), and protein precipitated with 350 microL acetonitrile. The sample was centrifuged and 30 microL aliquot was injected onto the HPLC column, where it underwent an online extraction with ammonium acetate. After that the automatic switching valve was activated, changing the mobile phase to methanol and thereby eluting the analytes into the tandem mass spectrometer. The high selectivity of a tandem mass analyzer allows determination of any combination of the three drugs within a 5 min run. RESULTS: Between-day precision was between 2.4% and 9.7% for all analytes at the concentrations tested. Accuracy ranged between 98.8% and 103.2% (n = 20). The method was linear over the measuring ranges of all analytes. Within-run precision was below %CV = 6% for all analytes. Good correlation with other analytical methods was observed. CONCLUSIONS: The simplicity, universality and high throughput of the method make it suitable for application in a clinical laboratory. The method has been implemented in our laboratory for a routine use.     

Chronic axillary hidradenitis--the efficacy of wide excision and flap coverage.

A number of different modalities of surgical treatment for axillary hidradenitis suppurativa have been suggested. This study compares three different methods of surgical excision. Fifty-nine patients (94 axillae) were treated over a 14-year period. There were 42 females and 17 males with an average age of 32 years (range 16-65 years). Twenty-six axillae had excision of only the diseased skin and recurrent disease occurred in seven. However, in 39 axillae that were treated by excision of all the hair bearing skin, only three developed recurrent disease, which is a significant reduction in the incidence of recurrent disease (P = 0.04, Fischer's exact test). Twenty-nine axillae were treated by wide local excision (2 cm beyond the hair bearing skin) and no recurrence occurred. However, there was no statistical difference (P = 0.18, Fischer's exact test) in disease recurrence between excision of all the hair bearing skin and wide local excision. This study suggests that excision of all the hair bearing skin is the preferred method of surgical treatment. Flap coverage was an effective method to achieve wound closure after adequate excision and can be achieved by random fasciocutaneous flaps for small or medium sized defects and parascapular flaps for large defects.     

Bacitracin attenuates haemolysis-induced insulin degradation during insulin sensitivity testing: Repurposing an old drug for use in metabolic research

Haemolysis of serially collected insulin serum samples frequently causes falsely-low measured concentrations because of the release of intracellular insulin degrading enzyme (IDE). We investigated if bacitracin, an in vitro IDE inhibitor, could prevent haemolysis-induced insulin degradation during insulin sensitivity testing. Blood samples were collected from adults undergoing serial sampling for insulin sensitivity. A dose-finding study measured insulin from experimentally haemolysed samples containing five bacitracin concentrations (0-2.5 g/L) and from non-experimentally haemolysed samples. To confirm the utility of bacitracin in the clinical setting, we compared insulin in samples collected with and without 1 g/L bacitracin from a frequently sampled intravenous glucose tolerance test (FSIVGTT), where haemolysis often occurs accidentally. In the dose-finding study, bacitracin 0.25, 1 and 2.5 g/L all maximally prevented insulin degradation in experimentally haemolysed samples. Among FSIVGTT unintentionally haemolysed samples, insulin concentrations from bacitracin-containing samples were significantly higher than from those without bacitracin (P < .01), and not different from non-haemolysed samples obtained simultaneously from a second intravenous catheter (P = .07). Bacitracin did not significantly alter insulin concentrations in non-haemolysed samples. Bacitracin attenuates haemolysis-associated insulin degradation in clinical samples, enabling a more accurate assessment of insulin sensitivity and glucose homeostasis.     

Enhanced Mg2+-ATPase activity in ghosts from HS erythrocytes and in normal ghosts stripped of membrane skeletal proteins may reflect enhanced aminophospholipid translocase activity

Hereditary spherocytosis (HS) is a congenital haemolytic anaemia which is characterized by a great variety of structural defects in the red cell's membrane skeleton and/or deficiencies in particular membrane (skeletal) proteins. Enhanced (Mg²⁺)-dependent adenosine triphosphatase (Mg²⁺-ATPase) activities, varying from 115% to 160%, were invariably found in erythrocyte ghosts derived from 13 HS patients. Similarly, an enhancement of Mg²⁺-ATPase activity by 30% is observed in normal red cell ghosts that have been stripped of the greater part of their membrane skeletal proteins by treatment with a low ionic strength buffer. Reassociation of those stripped ghosts with spectrin reduces the enhanced Mg²⁺-ATPase activity to its original level. Since in both cases, HS ghosts and stripped normal ghosts, the stabilizing effects that the membrane skeleton exerts on the maintenance of an endofacial localization of the aminophospholipids are impaired, the enhanced Mg²⁺-ATPase activity is interpreted to reflect an increased activity of the aminophospholipid translocase. The present observations therefore support a role of the membrane skeleton in the stabilization of phospholipid asymmetry in the red cell membrane and consequently in reducing the energy consumption of the translocase.     

A breast reconstruction needs assessment: How does self-efficacy affect information access and preferences?

BACKGROUND:

Breast cancer patients requiring mastectomy do not consistently receive information about post-mastectomy breast reconstruction (PMBR) surgery from the treatment team. Patients have varying levels of self-efficacy, defined as one’s confidence in their ability to gather information and make health-related decisions. The present preliminary study was designed to evaluate the relationship between self-efficacy and access to PMBR information.

METHODS:

A qualitative interview study was conducted on a convenience sample of 10 breast cancer patients considering or having already undergone PMBR and six key health care provider informants. The modified six-item Stanford Self-Efficacy Scale for managing chronic disease was administered.

RESULTS:

Patient self-efficacy scores ranged from 5 to 9.3 (out of 10). Two main access to information themes were identified from the patient qualitative data: theme A – difficulty initiating the PMBR discussion; and theme B – perceived lack of access to PMBR information with the sub-themes of timing, modality, quantity and content of resources. All respondents expressed their concern over the absence of a standardized process for initiating the dialogue of PMBR. Patients also reported that credible and easily accessible information was not routinely available and expressed a desire to hear about their PMBR options early in the decision-making process.

CONCLUSIONS:

Health care providers may need to assume more responsibility in standardizing information dissemination on PMBR. This information should be distributed early in the consultation process, the content should be complete, and there may be a role for individualizing the delivery of information based on a patient’s level of self-efficacy.