Blood usage in lung transplantation

BACKGROUND: Few published data are available regarding perioperative blood usage in lung transplantation. STUDY DESIGN AND METHODS: The medical records of all patients undergoing lung transplantation at a university medical center in 1994 and 1995 were reviewed. RESULTS: Ninety patients underwent lung transplantation during this period. Six patients were excluded: two received a living related-donor lung, three underwent retransplantation and one underwent concomitant repair of a tetralogy of Fallot. Of the 84 evaluable patients, 59 underwent single lung transplantation and 25 double lung transplantation. Double-lung recipients used more red cells (6.4 vs. 1.7 units, p = 0.0002) and were more likely to receive red cells, platelets, plasma, or any component (92 vs. 32%, p< or =0.0001) than were single-lung recipients. Double- lung recipients were more likely to require cardiopulmonary bypass (40 vs. 12%, p = 0.003), and cardiopulmonary bypass was associated with greater transfusion requirements (p< or =0.0001). However, among patients requiring cardiopulmonary bypass, blood use did not differ between those undergoing double lung transplantation and those undergoing single lung transplantation. In the subset of patients not requiring cardiopulmonary bypass, double-lung recipients received more red cells (4.5 vs. 0.7 units, p< or =0.0001) and more plasma (2.0 vs. 0.2 units, p = 0.006). CONCLUSION: Double-lung recipients require more perioperative transfusions than single-lung recipients. The greater transfusion requirement is due to the more frequent need for cardiopulmonary bypass as well as the greater complexity of the procedure. These data are useful for developing surgical blood ordering guidelines for lung transplantation.     

CENTRAL NEUROGENIC NEUROPROTECTION: PROTECTION OF BRAIN FROM FOCAL ISCHEMIA BY CEREBELLAR STIMULATION

Electrical stimulation of the cerebellar fastigial nucleus (FN) elevates regional cerebral blood flow (rCBF) independently of cerebral metabolism (rCGU) throughout brain. One hour of FN stimulation also reduces, by up to 50%, the volume of the focal ischemic infarction produced by occlusion of the middle cerebral artery in rat. Protected areas correspond to the ischemic penumbra. Neuroprotection, while reversible, persists for weeks after 1h of stimulation. It cannot be attributed to increasing rCBF and/or reducing rCGU to improve matching of flow and metabolism. Conditional stimulation of FN initiates long-lived inhibition of expression of peri-infarction depolarizing waves, possibly by altering potassium-channel function and suppresses induction of inducible nitric oxide synthase (iNOS) and ICAM in cerebral microvessels. The brain contains intrinsic networks which may protect the brain from ischemic injury, possibly by producing widespread and longterm suppression of electrical excitability and/or and expression of proinflammatory molecules.     

A rapid method for harvesting autologous red cells from patients with hemoglobin S disease

Red cells from patients with sickle cell disease (HbSS and HbSC) are more resistant to lysis in hypotonic NaCl solutions than normal (HbAA) red cells. Taking advantage of this inherent resistance to osmotic stress, patient red cells (HbSS or HbSC) were rapidly isolated from donor red cells (HbAA or HbAS) by washing with hypotonic (0.3%) NaCl. The hypotonic method of washing provides a previously unavailable means for obtaining autologous HbSS or HbSC red cells from samples containing transfused donor red cells. Once isolated, these red cells can be used for phenotyping, autoadsorption, or evaluation of positive direct antiglobulin tests.     

Van der Woude syndrome: dentofacial features and implications for clinical practice

Background:  Van der Woude syndrome (VWS) is the most common clefting syndrome in humans. It is characterized by the association of congenital lower lip fistulae with cleft lip and/or cleft palate. VWS individuals have a high prevalence of hypodontia. Although caused by a single gene mutation, VWS has variable phenotypic expression. This study aimed to describe the range of clinical presentations in 22 individuals with VWS to facilitate its diagnosis.
Methods:  A retrospective study of 22 patients with a diagnosis of VWS was undertaken at the Australian Craniofacial Unit (ACFU) in Adelaide. Three extended families with affected members were included in the study cohort.
Results:  The overall prevalence of lip pits in this study cohort was 86%. Cleft phenotypes included bilateral cleft lip and palate (32%); unilateral cleft lip and palate (32%); submucous cleft palate (23%); and isolated cleft hard and soft palate (9%). Missing permanent teeth were reported in 86% of affected individuals.
Conclusions:  Submucous cleft palate in VWS may go undiagnosed if the lower lip pits are not detected. Associated hypodontia and resultant malocclusions will also require management by a dental team.     

The impact of cytokines on the expression of drug transporters,cytochrome P450 enzymes and chemokine receptors in human PBMC

Background and purpose:

The function of transporters in peripheral blood mononuclear cells (PBMC) has been characterized, but less is known about cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are dysregulated in many diseases, the purpose of this work was to assess the impact of cytokines on the expression of CYPs, transporters and chemokine receptors in PBMC.

Experimental approach:

Human PBMC were incubated with cytokines for 48 h. ATP-binding cassette (ABC)B1, ABCC1, ABCC2, CYP2B6, CYP3A4, CXCR4 and CCR5 expression were measured by quantitative polymerase chain reaction and flow cytometry at 0, 4, 8, 24 and 48 h. Enzyme activity was assessed using fluorescent probes.

Key results:

We show here functional activity of CYP3A4 and CYP2B6 in PBMC. Furthermore, cytokines had a significant impact on the mRNA and protein expression of all proteins. For example, interleukin-2 (IL-2) had a marked impact on ABCB1 mRNA (% control 4745 ± 11961) and protein (% control 200 ± 57). Increases in drug efflux transporter expression, in response to cytokines, resulted in reduced cellular accumulation of digoxin [decrease of 17% and 26% for IL-2 and interferon-γ (IFNγ) respectively] and saquinavir (decrease of 28% and 30% for IL-2 and IFNγ respectively). The degree to which drug transporter and chemokine receptor expression changed in response to cytokines was positively correlated (e.g. ABCB1 and CXCR4, r² = 0.545).

Conclusions and implications:

These data have important implications for diseases in which cytokines are dysregulated and for which pharmacological intervention targets immune cells.     

Stage T1 glottic carcinoma: results of radiation therapy or laser excision

A retrospective analysis was made of the data on 60 patients with stage T1 glottic carcinoma (43 T1a, 17 T1b) who received radiation therapy and 17 patients with T1a disease who underwent laser excision as the primary treatment modality. Patients who received radiation therapy achieved 3- and 5-year actuarial local control rates of 92% and 89% for T1a and 77% and 77% for T1b disease, respectively. In patients who underwent laser excision (all with T1a disease), the 3-year local control rate was 77%. Of the 42 evaluable irradiated T1a patients, 31 (74%) had a normal to near-normal voice, eight (19%) had mild or intermittent hoarseness, and three (7%) had persistent hoarseness. Of the 13 evaluable patients in the laser-excision group, four (31%) had a normal to near-normal voice, five (38%) had mild or intermittent hoarseness, and four (31%) had persistent hoarseness. The difference in the quality of voice between these two groups is statistically significant (P = .012), although the ultimate local control rate after salvage therapy for irradiated patients (97%) was similar to that for laser-excision patients (94%).     

Ultrasound of the posterior circumflex humeral artery

Quadrilateral space syndrome (QSS) is described as compression neuropathy of the axillary neurovascular bundle in the quadrilateral space of the shoulder. This neurovascular bundle includes the posterior circumflex humeral artery (PCHA). Historically, angiography and more recently magnetic resonance angiography have been used to assess occlusion and stenosis of the PCHA in cases of suspected QSS. These traditional imaging techniques have a number of disadvantages in terms of cost, availability, invasiveness and patient comfort. We undertook to examine the ability of ultrasound to reliably visualise the PCHA. Asymptomatic adult volunteers were recruited from staff, and patients attending the radiology department who presented for pathologies unrelated to the shoulder. We used a new technique to assess blood flow in the PCHA, performing the scan from a posterolateral approach on the upper arm just above the level of the surgical neck of the humerus. This technique enabled the scan to be undertaken with the patient seated comfortably. Fifty volunteers were recruited into the study. The mean (±SD) age was 35 (±14 years). The PCHA was visualised in all patients. Our method was able to maximise Doppler sensitivity and visualisation of the artery without discomfort to the patient in less than 10 min. Ultrasound can be used to reliably visualise the PCHA. Ultrasound has potential to be used in the assessment of the PCHA in cases of QSS.