CARDIORESPIRATORY RESPONSES TO AN I.V. INFUSION OF DOBUTAMINE IN THE INTACT ANAESTHETIZED DOG

The cardiorespiratory responses to an I.V. infusion of dobutaminehydrochloride were assessed in eight anaesthetized, mechanicallyventilated dogs As the rate of infusion of dobutamine was increasedfrom 2 to 30 µg kg^–1min^–1, there was a progressivedecrease in arterial pressure, pulmonary wedge pressure andarterial pH. There was a significant decrease in arterial oxygentension at the greater doses of dobutamine (15 and 30 µgkg^–1min^–1) from initial control values. Carbon dioxide output,arterial carbon dioxide tension, venous admixture and oxygenconsumption increased during the infusion of dobutamine. However,oxygen supply increased further so that the oxygen consumption:supply ratio decreased It is concluded that dobutamine may decreasearterial oxygen tension, but that the increased cardiac outputand decreased arterial pH produced by dobutamine may increaseoxygen supply to the tissues in spite of this. ^*Present addresses: Department of Physiology, University CollegeLondon, Gower Street, London WC1E 6BT. Present addresses: Nuffield Department of Anaesthetics, RadcliffeInfirmary, Oxford 0X2 6HE.     

Unrelated donor bone marrow transplantation for children and adolescents with aplastic anaemia or myelodysplasia

Allogeneic transplantation from an HLA-matched family member has been shown to be effective in reconstituting normal haemopoiesis in young people with severe cytopenias, classified as myelodysplastic syndrome (MDS) or severe aplastic anaemia (SAA). Unrelated donor transplant is a therapeutic choice for patients without a suitable family member donor. We report the outcome of seven patients < 20 years old with SAA and 10 with MDS treated with BMT from an HLA A,B DRB1 matched ( n  =8) or A or B locus mismatched ( n  =9) unrelated donor at the University of Minnesota between March 1988 and August 1995. Primary graft failure occurred in two patients and secondary graft failure in one, who was subsequently successfully engrafted with a second donor marrow infusion. Grades II–IV GVHD occurred in 10/16 (63%), and grades III–IV in 6/16 (37%) evaluable patients. Nine of the 17 patients (six with MDS and three with SAA) survive with full donor chimaerism, a median of 1.2 years post-BMT (range 3 months to 7 years). We recommend early referral for consideration of unrelated donor BMT for young patients with MDS, and patients with SAA without response to immunosuppression.     

Solitary and generalized variants of spindle cell xanthogranuloma (progressive nodular histiocytosis)

Twelve cases of solitary spindle cell xanthogranuloma, seven of which had originally been misdiagnosed as dermatofibroma/benign fibrous histiocytoma, were clinicopathologically compared with four cases of progressive nodular histiocytosis, a rare generalized non-X histiocytic disorder. Clinically, a single brown-yellowish papule or nodule is characteristic of solitary spindle cell xanthogranuloma, multiple generalized lesions of progressive nodular histiocytosis. Solitary spindle cell xanthogranuloma occurs with decreasing frequency on the head, neck, upper trunk, or occasionally the extremities of young adults (aged 20–40 years), progressive nodular histiocytosis mostly on the trunk of older patients (aged 40–60 years), both without sex predilection. Histologically, both entities are characterized by predominance (> 90%) of spindle-shaped histiocytes arranged in a storiform pattern. Other mononuclear (vacuolated, xanthomatized, scalloped, oncocytic) and multinucleate (Touton) histiocytes are also regularly seen. Immunohistochemically, both entities exhibit a macrophage/dendritic cell lineage positive for KP1/Ki-M1p (CD68), HAM 56 and factor XIIIa as well as for smooth muscle specific actin and HHF35. Ultrastructurally, dense, regularly laminated, myeloid or pleomorphic cytoplasmic inclusions may be found, but no Birbeck granules are present. This study documents that both solitary spindle cell xanthogranuloma and progressive nodular histiocytosis are distinct entities within the spectrum of a xanthogranulomatous reaction characterized by predominance of spindle-shaped histiocytes.     

Do plant sterol concentrations correlate with coronary artery disease in type 1 diabetes? A report from the Pittsburgh Epidemiology of Diabetes Complications Study

Background:  It has been suggested that plant sterol absorption is increased in type 1 diabetes mellitus (T1DM) and that this may relate to the increased cardiovascular risk seen in T1DM. The cardiovascular benefit of lowering low‐density lipoprotein–cholesterol with statin medication has also been shown to be influenced by plant sterol absorption. Methods:  The relationship between sterol concentrations, coronary artery disease (CAD), and the use of statin medications in T1DM was compared between participants with CAD (Minnesota codes 1.1, 1.2, 1.3, 4.1–4.3, 5.1–5.3, and 7.1; n = 82), from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, and those without (n = 213). Serum sterol concentrations reflecting cholesterol absorption (β‐sitosterol and campesterol) and synthesis (desmosterol and lathosterol) were assayed and analyzed by gas chromatography and were expressed as a ratio of total cholesterol (×10³). Results:  No differences were observed in markers of cholesterol absorption between individuals with and without CAD. In patients with CAD, significantly lower levels were observed for both sterol markers reflecting cholesterol synthesis compared with individuals without CAD [desmosterol: 0.34 vs 0.42, respectively (P = 0.003); lathosterol 0.47 vs 0.54, respectively (P = 0.019)]. Further stratification by statin medication use revealed significantly lower levels of synthesis‐reflecting sterols in individuals taking statin medication, particularly those with CAD. Conclusions:  Although previous reports suggest that higher levels of cholesterol absorption in T1DM potentially increase cardiovascular risk in this population, the present data suggest no differences in cholesterol absorption between T1DM individuals with and without CAD.     

Persistent isolationist or collaborator? The nurse’s role in interprofessional collaborative practice

orchard ca . (2010) Journal of Nursing Management 18 , 248–257
Persistent isolationist or collaborator? The nurse’s role in interprofessional collaborative practice Aim The present study explores current understanding about interprofessional collaborative client-centred practice and nursing’s role in this form of care delivery. Background A profession-only focus on nursing practice has been challenged at professional, national governmental and World Health Organization levels stressing for more interprofessional patient-centred collaborative teamwork. Evaluation Moving to patient-centred collaborative practice is fraught with barriers. Enablers can result in building trust, power sharing and shared decision-making. Changing current workplace environments requires institutional commitments to support collaborative team development. Key issue(s) Nurses can become collaborative members of teams through: (1) re-socialize; (2) understanding and articulating nurses roles, knowledge and skills to others; (3) other health providers sharing the same to nurses; (4) identifying where shared roles, knowledge and skills exist; and (5) learning to work in collaborative teams. Nurses must address some fundamental issues about practice that negate collaboration and patient-centred care. Conclusions All professionals, including nurses, must move away from a service-oriented delivery to a patient-centred collaborative approach to care. Implications for nursing management The values within health organizations need to be underpinned by collaborative interprofessional patient-centred practice. To accomplish this goal, administrators and managers must support assessment of employees and visiting physicians as to their conformance with agency established expectations for such practice.     

Acidosis Impairs the Protective Role of hERG K+ Channels Against Premature Stimulation

Acidosis and the hERG K⁺ Channel . Introduction: Potassium channels encoded by human ether‐à‐go‐go‐related gene (hERG) underlie the cardiac rapid delayed rectifier K⁺ channel current (I_Kr). Acidosis occurs in a number of pathological situations and modulates a range of ionic currents including I_Kr. The aim of this study was to characterize effects of extracellular acidosis on hERG current (I_hERG), with particular reference to quantifying effects on I_hERG elicited by physiological waveforms and upon the protective role afforded by hERG against premature depolarizing stimuli. Methods and Results: I_hERG recordings were made from hERG‐expressing Chinese Hamster Ovary cells using whole‐cell patch‐clamp at 37°C. I_hERG during action potential (AP) waveforms was rapidly suppressed by reducing external pH from 7.4 to 6.3. Peak repolarizing current and steady state I_hERG activation were shifted by ～+6 mV; maximal I_hERG conductance was reduced. The voltage‐dependence of I_hERG inactivation was little‐altered. Fast and slow time‐constants of I_hERG deactivation were smaller across a range of voltages at pH 6.3 than at pH 7.4, and the contribution of fast deactivation increased. A modest acceleration of the time‐course of recovery of I_hERG from inactivation was observed, but time‐course of activation was unaffected. The amplitude of outward I_hERG transients elicited by premature stimuli following an AP command was significantly decreased at lower pH. Computer simulations showed that after AP repolarization a subthreshold stimulus at pH 7.4 could evoke an AP at pH 6.3. Conclusion: During acidosis the contribution of I_hERG to action potential repolarization is reduced and hERG may be less effective in counteracting proarrhythmogenic depolarizing stimuli. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1160‐1169)