Hepatopulmonary syndrome in candidates for liver transplantation

BACKGROUND: Hepatopulmonary syndrome (HPS) has been defined as a clinical triad, including chronic liver disease, gas exchange defects (increased alveolar-arterial PO2 difference irrespective of the presence of arterial hypoxemia), and widespread intrapulmonary vascular dilatations. We determined the incidence and the clinical and pulmonary functional characteristics of HPS in candidates for orthotopic liver transplantation (OLT) and tested their predicted accuracy. METHODS: We studied 80 patients with cirrhosis prospectively, and carried out contrast-enhanced (CE) echocardiography and lung function tests, including ventilation-perfusion (V(A)/Q) distributions. RESULTS: Fourteen patients had HPS (incidence, 17.5%). Patients with HPS (49 +/- 12 (+/-SD) years) had more cutaneous spiders, finger clubbing and dyspnea (P < 0.05 each) and a lower diffusing capacity (DLCO, 56 +/- 18% predicted; P < 0.001) than non-HPS patients (n = 66). Mild to moderate V(A)/Q inequalities and increased intrapulmonary shunt were predominant in HPS patients, but oxygen diffusion impairment was observed in those with hypoxemia (n = 8) only. The DLCO showed a considerable area under the receiver operating characteristic curve (0.89). CONCLUSIONS: HPS in cirrhotic patient candidates for OLT shows a high incidence and these patients present with distinctive clinical and functional features compared with non-HPS individuals. The presence of a low DLCO may be of help for the diagnosis of HPS.     

Blockade of cardiac sodium channels by amitriptyline and diphenylhydantoin. Evidence for two use-dependent binding sites.

Cardiac toxicity is a frequent manifestation in amitriptyline overdose and is felt to be due, in part, to sodium channel blockade by the drug. Another agent with sodium channel blocking properties, diphenylhydantoin, has been used clinically to reverse cardiac conduction abnormalities induced by amitriptyline. This reversal of toxicity is believed to occur secondary to competition for the sodium channel binding site. We evaluated individually and in combination the effects of amitriptyline (0.4 microM) and diphenylhydantoin (10-80 microM) on the sodium current in isolated rabbit atrial and ventricular myocytes at 17 degrees C. Using the whole-cell variant of the patch-clamp technique, we found that both amitriptyline and diphenylhydantoin reduced the sodium current in a use-dependent fashion. The time constant of recovery (tau r) from block by amitriptyline at -130 mV was very slow (13.6 +/- 3.2 seconds), whereas tau r during diphenylhydantoin exposure was fast (0.71 +/- 0.21 seconds, p less than 0.0001 compared with amitriptyline). During exposure of cells to a mixture of the two drugs, tau r was found to be 6.6 +/- 1.8 seconds, but no evidence of direct competition between amitriptyline and diphenylhydantoin was seen. Attempts to fit the recovery data of the mixture to two exponentials resulted in no significant improvement in the fit when compared with that using a single exponential. Use of the sodium channel blocking agent lidocaine (similar kinetics to diphenylhydantoin) in competition with amitriptyline resulted in findings consistent with direct competition of these two drugs for a single binding site. These observations prompted us to evaluate the possibility that diphenylhydantoin was not acting at (and therefore not competing for) the same channel binding site as amitriptyline. Experiments altering pHi and pHo revealed dramatic differences between amitriptyline and diphenylhydantoin. When pHo was increased from 7.4 to 8.0, tau r was reduced approximately threefold (from 13.6 +/- 3.2 to 4.2 +/- 0.1 seconds, p less than 0.0001) during exposure to amitriptyline, but no effect was seen on tau r after exposure to diphenylhydantoin. Conversely, when pHi was increased from 7.3 to 8.0, tau r after amitriptyline was unaffected, but tau r after diphenylhydantoin markedly increased (from 0.71 +/- 0.21 to 2.60 +/- 1.30 seconds, p less than 0.001). Additionally, diphenylhydantoin block demonstrated profound voltage dependence across the range of -130 to -90 mV, whereas amitriptyline block appeared less voltage sensitive. Single-channel studies using patch-clamp techniques in isolated ventricular myocytes supported these data.(ABSTRACT TRUNCATED AT 400 WORDS)     

Bone marrows of non-Hodgkin's lymphoma patients with a bcl-2 translocation can be purged of polymerase chain reaction-detectable lymphoma cells using monoclonal antibodies and immunomagnetic bead depletion.

Using the extremely sensitive technique of polymerase chain reaction (PCR) to detect the bcl-2 translocation, only 50% of bone marrows could be purged of PCR-detectable lymphoma cells using a cocktail of three anti-B-cell monoclonal antibodies (MoAbs) and complement-mediated lysis. This observation is of clinical importance because those patients whose reinfused marrows harbored residual lymphoma cells showed a significantly increased incidence of relapse. To improve purging, we used PCR detection of the bcl-2 translocation to compare the efficiency of complement-mediated lysis with immunomagnetic bead depletion. Using either a three or a four MoAb cocktail followed by immunomagnetic bead depletion, all PCR-detectable cells were purged after three cycles of treatment. In these same patient samples, treatment with three MoAbs and complement purged only 11 of the 25 (44%) samples. The addition of a fourth MoAb followed by complement lysis purged the marrows of only an additional five patients. Immunomagnetic bead depletion was specific because there was no loss of committed myeloid progenitor cells. The above results suggest that immunomagnetic bead depletion of the harvested marrow will likely be superior to our previous method of purging and the lack of nonspecific toxicity to myeloid progenitor cells predicts that it will not impair engraftment. This methodology will now be used to determine whether the reinfusion of lymphoma free marrow affects the incidence of relapse after autologous bone marrow transplantation.     

Functional Capacity in Adults With Cerebral Palsy: Lower Limb Muscle Strength Matters

Objective

To investigate the relation between lower limb muscle strength, passive muscle properties, and functional capacity outcomes in adults with cerebral palsy (CP).

Electronic Inventory Systems and Barcode Technology: Impact on Pharmacy Technical Accuracy and Error Liability

Purpose:

To measure the effects associated with sequential implementation of electronic medication storage and inventory systems and product verification devices on pharmacy technical accuracy and rates of potential medication dispensing errors in an academic medical center.

Methods:

During four 28-day periods of observation, pharmacists recorded all technical errors identified at the final visual check of pharmaceuticals prior to dispensing. Technical filling errors involving deviations from order-specific selection of product, dosage form, strength, or quantity were documented when dispensing medications using (a) a conventional unit dose (UD) drug distribution system, (b) an electronic storage and inventory system utilizing automated dispensing cabinets (ADCs) within the pharmacy, (c) ADCs combined with barcode (BC) verification, and (d) ADCs and BC verification utilized with changes in product labeling and individualized personnel training in systems application.

Results:

Using a conventional UD system, the overall incidence of technical error was 0.157% (24/15,271). Following implementation of ADCs, the comparative overall incidence of technical error was 0.135% (10/7,379; P = .841). Following implementation of BC scanning, the comparative overall incidence of technical error was 0.137% (27/19,708; P = .729). Subsequent changes in product labeling and intensified staff training in the use of BC systems was associated with a decrease in the rate of technical error to 0.050% (13/26,200; P = .002).

Conclusions:

Pharmacy ADCs and BC systems provide complementary effects that improve technical accuracy and reduce the incidence of potential medication dispensing errors if this technology is used with comprehensive personnel training.     

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

AIMS

Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition.

METHODS

Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken.

RESULTS

One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m⁻². Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide.

CONCLUSIONS

Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required.     

Subcostal two-dimensional echocardiographic identification of anomalous attachment of septum primum in patients with left atrioventricular valve underdevelopment

Five variations of atrial septal morphology occur in hypoplastic left heart syndrome. One variety, termed anomalous attachment of septum primum, has been described only in necropsy series. Two-dimensional echocardiography was utilized to determine the incidence of this anomaly in patients with left atrioventricular (AV) valve underdevelopment, including those with other ventriculoarterial alignments, such as transposition of the great arteries. Forty-eight (37%) of 129 patients with normally aligned great arteries (and two ventricles) had anomalous attachment of septum primum. Ten (34%) of 29 patients with double outlet right ventricle and left AV valve underdevelopment had this anomaly. Four (50%) of eight patients with single ventricle exhibited this atrial septal variant. The most reliable view to identify anomalous attachment was the subcostal left oblique-equivalent cut. Recognition of atrial septal morphology has implications for preoperative and intraoperative management of patients with left AV valve underdevelopment. The similar prevalence of this atrial septal variant in patients with normally aligned great arteries, double outlet right ventricle and transposed great arteries suggests that there may be a common mechanism for left AV valve underdevelopment that is independent of the development of the arterial portion of the heart.